SIST EN ISO 5840:2006

SLOVENSKI STANDARD
SIST EN ISO 5840:2006
01-februar-2006
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SIST EN 12006-1:2000
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Cardiovascular implants - Cardiac valve prostheses (ISO 5840:2005)
Herz- und Gefäßimplantate - Herzklappenprothesen (ISO 5840:2005)
Implants cardiovasculaires - Protheses valvulaires (ISO 5840:2005)
Ta slovenski standard je istoveten z: EN ISO 5840:2005
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
SIST EN ISO 5840:2006 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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EUROPEAN STANDARD
EN ISO 5840
NORME EUROPÉENNE
EUROPÄISCHE NORM
December 2005
ICS 11.040.40 Supersedes EN 12006-1:1999
English Version
Cardiovascular implants - Cardiac valve prostheses (ISO
5840:2005)
Implants cardiovasculaires - Prothèses valvulaires (ISO Herz- und Gefäßimplantate - Herzklappenprothesen (ISO
5840:2005) 5840:2005)
This European Standard was approved by CEN on 28 February 2005.
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 Central Secretariat 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 Central Secretariat has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,
Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia,
Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2005 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 5840:2005: E
worldwide for CEN national Members.

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EN ISO 5840:2005 (E)




Foreword



The text of ISO 5840:2005 has been prepared by Technical Committee ISO/TC 150 "Implants for surgery" of
the International Organization for Standardization (ISO) and has been taken over as EN ISO 5840:2005 by
Technical Committee CEN/TC 285 "Non-active surgical implants", the secretariat of which is held by NEN.

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 June 2006, and conflicting national standards shall be withdrawn at
the latest by June 2006.

This document supersedes EN 12006-1:1999.

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 Directive(s), see informative Annex ZA, which is 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, Cyprus, Czech Republic,
Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland
and United Kingdom.



Endorsement notice

The text of ISO 5840:2005 has been approved by CEN as EN ISO 5840:2005 without any modifications.


2

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EN ISO 5840:2005 (E)

ANNEX ZA
(informative)

Relationship between this International Standard and the Essential
Requirements of EU Directive 93/42


By agreement between ISO and CEN, this CEN annex is included in the DIS and the FDIS but will not
appear in the published ISO standard.


This International Standard has been prepared under a mandate given to CEN by the European Commission
to provide one means of conforming to Essential Requirements of the New Approach Directive 93/42.

Once this standard is cited in the Official Journal of the European Communities 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 given in Table ZA.1 confers, within the limits of the scope of this standard, a
presumption of conformity with the corresponding Essential Requirements of that Directive and associated
EFTA regulations.
Table ZA.1 — Correspondence between this International Standard and Directive 93/42
Clauses/Subclauses Essential Requirements Qualifying remarks/Notes
of the Standard of Directive 93/42
5 1, 2, 3, 6
6.1 1, 3
6.2.1 and 6.2.2 3, 4 Procedure for quality system (design input) aiming at
supporting general ERs 3 and 4
6.2.3 with annex P 3, 5, 8.1, 8.3
6.2.3 with annex Q 13.1, 13.3, 13.4, 13.5, 13.6
6.2.3 with annex S 8.1, 8.3, 8.4
6.3 and 6.4 Elements of procedure for Quality system aiming at
supporting all safety and performance ERs
6.5 Elements of procedure for risk management
7.1, 7.2.1 Elements of procedure for quality system aiming at
supporting all safety and performance ERs
7.2.2 1, 7.1, 8.2, 9.2, 12.7.1
7.2.3 3, 4
7.2.4 3, 4, 9.2, 12.7.1
7.3 1, 6 Preclinical in vivo evaluation also aims at reducing the
risks for human subjects undergoing clinical
investigations
7.4 with annex R 14

WARNING: Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.
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INTERNATIONAL ISO
STANDARD 5840
Fourth edition
2005-03-01


Cardiovascular implants — Cardiac valve
prostheses
Implants cardiovasculaires — Prothèses valvulaires





Reference number
ISO 5840:2005(E)
©
ISO 2005

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ISO 5840:2005(E)
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ii © ISO 2005 – All rights reserved

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ISO 5840:2005(E)
Contents Page
Foreword. v
Introduction . vi
1 Scope. 1
2 Normative references. 1
3 Terms and definitions. 2
4 Abbreviations. 10
5 Fundamental requirements. 11
6 Device description. 11
6.1 Intended use. 11
6.2 Design inputs. 11
6.2.1 Operational specifications. 11
6.2.2 Performance specifications. 12
6.2.3 Packaging, labelling, and sterilization . 13
6.3 Design outputs. 13
6.3.1 General. 13
6.3.2 Examples of components of some heart valve substitutes . 13
6.4 Design transfer (manufacturing qualification). 14
6.5 Risk management. 14
6.5.1 Hazard identification. 14
6.5.2 Failure mode identification. 14
6.5.3 Risk estimation. 15
6.5.4 Risk evaluation. 15
6.5.5 Risk control. 15
6.5.6 Risk review. 15
7 Verification testing and analysis/Design validation . 15
7.1 General requirements. 15
7.2 In vitro assessment. 16
7.2.1 Test conditions, sample selection and reporting requirements . 16
7.2.2 Material property assessment. 16
7.2.3 Hydrodynamic performance assessment. 17
7.2.4 Structural performance assessment. 18
7.3 Preclinical in vivo evaluation. 19
7.3.1 Overall requirements. 19
7.3.2 Methods. 20
7.3.3 Test report. 20
7.4 Clinical investigation. 21
7.4.1 Principle. 21
7.4.2 General. 21
7.4.3 Number of institutions. 21
7.4.4 Number of patients . 21
7.4.5 Duration of the study. 22
7.4.6 Clinical data requirements. 22
7.4.7 Clinical investigation report. 24
Annex A (informative) Rationale for the provisions of this International Standard . 26
Annex B (informative) Heart valve substitute hazards, associated failure modes and
evaluation methods . 29
Annex C (informative) Risk assessment guidelines . 31
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ISO 5840:2005(E)
Annex D (informative) Examples and definitions of some physical and material properties of heart
valve substitutes and their components .38
Annex E (informative) Statistical procedures when using performance criteria .43
Annex F (informative) In vitro procedures for testing unstented or similar valves
in compliant chambers .44
Annex G (informative) Preclinical in vivo tests.46
Annex H (informative) Echocardiographic protocol.49
Annex I (informative) Description of the heart valve substitute.52
Annex J (informative) Figures of examples of components of some heart valve substitutes .54
Annex K (informative) Examples of standards applicable to testing of materials and components
of some heart valve substitutes.57
Annex L (informative) Guidelines for verification of hydrodynamic performance .63
Annex M (informative) Durability testing.69
Annex N (informative) Examples of design specific testing.71
Annex O (informative) Fatigue assessment .73
Annex P (normative) Packaging.77
Annex Q (normative) Labelling and instructions for use .78
Annex R (normative) Methods of evaluating clinical data.80
Annex S (normative) Sterilization .82
Bibliography.83

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ISO 5840:2005(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 5840 was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This fourth edition cancels and replaces the third edition (ISO 5840:1996), which has been technically revised
to include risk management.
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ISO 5840:2005(E)
Introduction
There is, as yet, no heart valve substitute that can be regarded as ideal.
This International Standard has been prepared by a group well aware of the problems associated with heart
valve substitutes and their development. In several areas, the provisions of this International Standard have
been deliberately left open as there has been no wish to inhibit development and innovation. It does specify
types of tests, test methods and/or requirements for test apparatus, and requires documentation of test
methods and results. The areas with which this International Standard is concerned are those which will
ensure that associated risks to the patient and other users of the device have been adequately mitigated,
facilitate quality assurance, aid the surgeon in choosing a heart valve substitute, and ensure that the device
will be presented at the operating table in a convenient form. Emphasis has been placed on specifying types
of in vitro testing, on preclinical in vivo and clinical evaluations, on reporting of all in vitro, preclinical in vivo
and clinical evaluations and on the labelling and packaging of the device. Such a process involving in vitro,
preclinical in vivo and clinical evaluations is intended to clarify the required procedures prior to market release
and to enable prompt identification and management of any subsequent problems.
With regard to in vitro testing and reporting, apart from basic material testing for mechanical, physical,
chemical and biocompatibility characteristics, this International Standard also covers important hydrodynamic
and durability characteristics of heart valve substitutes. The exact test methods for hydrodynamic and
durability testing have not been specified, but guidelines for the test apparatus are given.
This International Standard is incomplete in several areas. It is intended to be revised, updated, and/or
amended, as knowledge and techniques in heart valve substitute technology improve.
Annexes A to S provide supplementary information, the content of Annexes P to S being necessary for the
application of this International Standard.

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INTERNATIONAL STANDARD ISO 5840:2005(E)

Cardiovascular implants — Cardiac valve prostheses
1 Scope
1.1 This International Standard is applicable to all devices intended for implantation in human hearts, as a
heart valve substitute.
1.2 This International Standard is applicable to both newly developed and modified heart valve substitutes
and to the accessory devices, packaging and labelling required for their implantation and for determining the
appropriate size of heart valve substitute to be implanted.
1.3 This International Standard outlines an approach for qualifying the design and manufacture of a heart
valve substitute through risk management. The selection of appropriate qualification tests and methods are
derived from the risk assessment. The tests may include those to assess the physical, chemical, biological
and mechanical properties of heart valve substitutes and of their materials and components. The tests may
also include those for pre-clinical in vivo evaluation and clinical evaluation of the finished heart valve substitute.
1.4 This International Standard imposes design specifications and minimum performance specifications for
heart valve substitutes where adequate scientific and/or clinical evidence exists for their justification.
1.5 This International Standard excludes heart valve substitutes designed for implantation in artificial hearts
or heart assist devices.
NOTE A rationale for the provisions of this International Standard is given in Annex A.
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 8601:2000, Data elements and interchange formats — Information interchange — Representation of
dates and times
ISO 10993-1:1997, Biological evaluation of medical devices — Part 1: Evaluation and testing
ISO 10993-2:1992, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 11134:1994, Sterilization of health care products — Requirements for validation and routine control —
Industrial moist heat sterilization
ISO 11135:1994, Medical devices — Validation and routine control of ethylene oxide sterilization
ISO 11137:1995, Sterilization of health care products — Requirements for validation and routine control —
Radiation sterilization
ISO 11607:2003, Packaging for terminally sterilized medical devices
ISO 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 14155-1:2003, Clinical investigation of medical devices for human subjects — Part 1: General requirements
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ISO 5840:2005(E)
ISO 14160, Sterilization of single-use medical devices incorporating materials of animal origin — Validation
and routine control of sterilization by liquid chemical sterilants
1)
ISO 14630:— , Non-active surgical implants — General requirements
ISO 14937:2000, Sterilization of health care products — General requirements for characterization of a
sterilizing agent and the development, validation and routine control of a sterilization process for medical
devices
ISO 14971:2000, Medical devices — Application of risk management to medical devices
EN 12442-1, Animal tissues and their derivatives utilized in the manufacture of medical devices — Part 1:
Analysis and management of risk
EN 12442-2, Animal tissues and their derivatives utilized in the manufacture of medical devices — Part 2:
Controls on sourcing, collection and handling
EN 12442-3, Animal tissues and their derivatives utilized in the manufacture of medical devices — Part 3:
Validation of the elimination and/or inactivation of viruses and transmissible agents
Guidelines for reporting morbidity and mortality after cardiac valvular operations, American Association for
Thoracic Surgery, European Association for Cardiothoracic Surgery, Society of Thoracic Surgeons, Annals of
Thoracic Surgery, 62, pp. 932-935, 1996
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
accessories
device-specific tools that are required to assist in the implantation of the heart valve substitute
3.2
actuarial
statistical technique for estimating survival curves prior to the death of the last member of a cohort
NOTE Some examples are the “Kaplan-Meier” technique and the “life-table” technique.
3.3
anticoagulant-related haemorrhage
internal or external bleeding that causes death or stroke, or that requires transfusion, operation or
hospitalization
NOTE This definition is restricted to patients who are receiving anticoagulants and/or antiplatelet drugs, and excludes
minor bleeding events.
3.4
arterial diastolic pressure
minimum value of the arterial pressure during diastole
3.5
arterial peak systolic pressure
maximum value of the arterial pressure during systole

1) To be published. (Revision of ISO 14630:1997)
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ISO 5840:2005(E)
3.6
back pressure
differential pressure applied across the closed valve
3.7
blood-equivalent fluid
fluid whose physical properties, e.g. specific gravity, viscosity, approximate those of blood
3.8
closing volume
component of the regurgitant volume that is associated with the dynamics of valve closure during a single
cycle
See Figure 1.
3.9
control valve
heart valve substitute for preclinical and clinical evaluations of similar design and constructed of similar
material as the investigational device
NOTE The control valve should have a known clinical history.

Key
X time
Y flowrate
1 closing volume
2 leakage volume
Figure 1 — Schematic representation of flow waveform and regurgitant volumes for one cycle
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ISO 5840:2005(E)
3.10
cumulative incidence
statistical technique where events other than death can be described by the occurrence of the event over time
without including death of the subjects
NOTE Cumulative incidence is also known as ‘actual’ analysis.
3.11
cycle
one complete sequence in the action of a heart valve substitute under pulsatile-flow conditions
3.12
cycle rate
number of complete cycles per unit of time, usually expressed as cycles per minute (cycles/min)
3.13
design verification
establishment by objective evidence that the design output meets the design input requirements
3.14
design validation
establishment by objective evidence that device specifications conform with user needs and intended use(s)
3.15
effective orifice area
A
EO
orifice area that has been derived from flow and pressure or velocity data
3.16
failure
inability of a device to perform its intended function at any point during its intended lifetime
NOTE The inability to perform the intended function may manifest itself as a reduced operating effectiveness and/or
as hazards.
3.17
failure mode
mechanism of failure which can result in a hazard
NOTE Stent fracture, calcification and prolapse are examples of failure modes.
3.18
flexible heart valve substitute
heart valve substitute wherein the occluder is flexible under physiological conditions
NOTE The orifice ring may or may not be flexible. This category was previously known as biological heart valve
substitute because of the biological source of the flexible occluder(s) but, at a minimum, should also include flexible
polymer occluder(s).
3.19
forward-flow phase
portion of the cycle time during which forward flow occurs through a heart valve substitute
3.20
hazard
known or potential source of harm which results from a given failure mode
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ISO 5840:2005(E)
3.21
harm
physical injury or damage to the health of the patient or end-user of the device
[14]
NOTE Adapted from ISO/IEC Guide 51:
...