SIST EN ISO 5840-1:2015

Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements (ISO 5840-1:2015)

This part of ISO 5840 is applicable to heart valve substitutes intended for human implantation and
provides general requirements. Subsequent parts of the ISO 5840–series provide specific requirements.
This part of ISO 5840 is applicable to both newly developed and modified heart valve substitutes and
to the accessories, packaging, and labelling required for their implantation and for determining the
appropriate size of the heart valve substitute to be implanted.
This part of ISO 5840 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 preclinical in vivo evaluation and clinical evaluation of the finished
heart valve substitute.
This part of ISO 5840 defines operational conditions for heart valve substitutes.
This part of ISO 5840 excludes homografts.
NOTE A rationale for the provisions of this part of ISO 5840 is given in Annex A.

Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 1: Allgemeine Anforderungen (ISO 5840-1:2015)

Implants cardiovasculaires - Prothèses valvulaires - Partie 1: Exigences générales (ISO 5840-1:2015)

ISO 5840-1:2015 s'applique aux prothèses valvulaires destinées à une implantation chez l'homme et indique des exigences générales. Les exigences spécifiques figurent dans les parties qui succèdent à la présente partie de l'ISO 5840.
ISO 5840-1:2015 s'applique à la fois aux prothèses valvulaires récemment mises au point et à celles qui ont été modifiées, ainsi qu'aux accessoires, à l'emballage et à l'étiquetage exigés pour leur implantation et pour la détermination de la taille appropriée de la prothèse valvulaire à implanter.
ISO 5840-1:2015 souligne une approche destinée à qualifier la conception et la fabrication d'une prothèse valvulaire à travers la gestion des risques. La sélection des méthodes et des essais de qualification appropriés se fait à partir de l'appréciation du risque. Les essais peuvent inclure les essais destinés à évaluer les propriétés physiques, chimiques, biologiques et mécaniques des prothèses valvulaires ainsi que de leurs matériaux et composants. Les essais peuvent également englober les essais destinés à l'évaluation préclinique in vivo et à l'évaluation clinique des prothèses valvulaires à l'état fini.
ISO 5840-1:2015 définit les conditions de fonctionnement des prothèses valvulaires.
ISO 5840-1:2015 exclut les allogreffes.
NOTE Une justification des dispositions de la présente partie de l'ISO 5840 est donnée dans l'Annexe A.

Vsadki (implantati) za srce in ožilje - Proteze za srčno zaklopko - 1. del: Splošne zahteve (ISO 5840-1:2015)

Ta del standarda ISO 5840 velja za nadomestke srčne zaklopke, namenjene vsaditvi v človeško telo, in
določa splošne zahteve. Nadaljnji deli skupine standardov ISO 5840 določajo posebne zahteve. Ta del standarda ISO 5840 velja tako za na novo razvite in modificirane nadomestke srčne zaklopke kot tudi za dodatne naprave, zahteve glede pakiranja in označevanja za vsaditev ter določanje ustrezne velikosti nadomestka srčne zaklopke za vsaditev.
Ta del standarda ISO 5840 določa pristop za potrjevanje oblike in izdelave nadomestka srčne zaklopke v skladu z obvladovanjem tveganj. Izbor ustreznih preskusov in metod za potrjevanje se izpelje iz ocene tveganja. Preskusi lahko vključujejo preskuse za oceno fizikalnih, kemičnih, bioloških in mehanskih lastnosti nadomestkov srčne zaklopke ter drugih materialov in sestavin.
Preskusi lahko vključujejo tudi preskuse za predklinično oceno in vivo ter klinično oceno končanega nadomestka srčne zaklopke.
Ta del standarda ISO 5840 opredeljuje obratovalne pogoje nadomestkov srčne zaklopke.
Ta del standarda ISO 5840 izključuje homografte.
OPOMBA: pojasnilo določb tega dela standarda ISO 5840 je podano v dodatku A.

General Information

• Status: Withdrawn
• Public Enquiry End Date: 09-Jul-2014
• Publication Date: 02-Nov-2015
• Withdrawal Date: 17-Feb-2021
• ICS: 11.040.40 - Implants for surgery, prosthetics and orthotics
• Technical Committee: VAZ - Healthcare
• Current Stage: 9900 - Withdrawal (Adopted Project)
• Start Date: 17-Feb-2021
• Due Date: 12-Mar-2021
• Completion Date: 18-Feb-2021
• Directive: 2007/47/EC - Directive 2007/47/EC of the European Parliament and of the council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• Mandate: M/023 - Standardization mandate to CEN/CENELEC concerning the development of European standards relating to medical devices
• Ref Project: EN ISO 5840-1:2015 - Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements (ISO 5840-1:2015)

Relations

• Revised: SIST EN ISO 5840:2009 - Cardiovascular implants - Cardiac valve prostheses (ISO 5840:2005)
• Effective Date: 01-Dec-2015
• Replaced By: SIST EN ISO 5840-1:2021 - Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements (ISO 5840-1:2021)
• Effective Date: 01-Mar-2021

Standards Content (Sample)

SLOVENSKI STANDARD
SIST EN ISO 5840-1:2015
01-december-2015
9VDGNLLPSODQWDWL]DVUFHLQRåLOMH3URWH]H]DVUþQR]DNORSNRGHO6SORãQH
]DKWHYH,62
Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements (ISO
5840-1:2015)
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 1: Allgemeine Anforderungen
(ISO 5840-1:2015)
Implants cardiovasculaires - Prothèses valvulaires - Partie 1: Exigences générales (ISO
5840-1:2015)
Ta slovenski standard je istoveten z: EN ISO 5840-1:2015
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
SIST EN ISO 5840-1:2015 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 5840-1:2015

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SIST EN ISO 5840-1:2015


EN ISO 5840-1
EUROPEAN STANDARD

NORME EUROPÉENNE

September 2015
EUROPÄISCHE NORM
ICS 11.040.40
English Version

Cardiovascular implants - Cardiac valve prostheses - Part
1: General requirements (ISO 5840-1:2015)
Implants cardiovasculaires - Prothèses valvulaires - Herz- und Gefäßimplantate - Herzklappenprothesen -
Partie 1: Exigences générales (ISO 5840-1:2015) Teil 1: Allgemeine Anforderungen (ISO 5840-1:2015)
This European Standard was approved by CEN on 10 July 2015.

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, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.





EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 5840-1:2015 E
worldwide for CEN national Members.

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SIST EN ISO 5840-1:2015
EN ISO 5840-1:2015 (E)
Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices . 4

2

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SIST EN ISO 5840-1:2015
EN ISO 5840-1:2015 (E)
European foreword
This document (EN ISO 5840-1:2015) has been prepared by Technical Committee ISO/TC 150
“Implants for surgery” in collaboration with Technical Committee CEN/TC 285 “Non-active surgical
implants” 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 March 2016, and conflicting national standards shall
be withdrawn at the latest by March 2016.
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 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, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 5840-1:2015 has been approved by CEN as EN ISO 5840-1:2015 without any
modification.
3

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SIST EN ISO 5840-1:2015
EN ISO 5840-1:2015 (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 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 European Standard
and Directive 93/42/EEC on medical devices
Clause(s)/sub-clause(s) Essential Requirements (ERs) Qualifying remarks/Notes
of this European Standard of Directive 93/42/EEC
5, 6, 7 7.1
5, 6.2.4, 6.4, 6.5 7.2
6.2.2, 6.2.3, 7.3 7.3
6.5 7.5
6.2.2, 6.5 7.6
5, 6.4, 6.5 8.1
6.2.4, 6.4 8.3
6.2.4 8.4
6.4 8.5
6.2.4 8.6
6.2.4 8.7
6.2.1, 6.3, 7 9.1
6.2.1, 6.3, 6.4, 6.5, 7 9.2, 1. indent
6.4, 6.5, 7 9.2, 2. indent
6.4, 6.5, 7 9.2, 3. indent
6.2.1, 6.3, 6.4, 6.5, 7 9.2, 4. indent
6.2.4 13
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 5840-1:2015
INTERNATIONAL ISO
STANDARD 5840-1
First edition
2015-09-15
Cardiovascular implants — Cardiac
valve prostheses —
Part 1:
General requirements
Implants cardiovasculaires — Prothèses valvulaires —
Partie 1: Exigences générales
Reference number
ISO 5840-1:2015(E)
©
ISO 2015

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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(E)

COPYRIGHT PROTECTED DOCUMENT
© ISO 2015, Published in Switzerland
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
Ch. de Blandonnet 8 • CP 401
CH-1214 Vernier, Geneva, Switzerland
Tel. [phone]
Fax [phone]
[e-mail]
www.iso.org
ii © ISO 2015 – All rights reserved

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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(E)

Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviations.11
5 Fundamental requirements .12
6 Device description .12
6.1 Intended use .12
6.2 Design inputs .12
6.2.1 Operational specifications .12
6.2.2 Performance specifications .12
6.2.3 Implant procedure.12
6.2.4 Packaging, labelling, and sterilization .13
6.3 Design outputs .13
6.4 Design transfer (manufacturing verification/validation) .14
6.5 Risk management .14
7 Design verification testing and analysis/design validation .15
7.1 General requirements .15
7.2 In vitro assessment .15
7.3 Preclinical in vivo evaluation .15
7.4 Clinical investigations .15
Annex A (informative) Rationale for the provisions of this part of ISO 5480 .16
Annex B (normative) Packaging .19
Annex C (normative) Product labels, instructions for use, and training .20
Annex D (normative) Sterilization .23
Annex E (informative) In vitro test guidelines for paediatric devices .24
Annex F (informative) Statistical procedures when using in vitro performance criteria .28
Annex G (informative) Examples and definitions of some physical and material properties
of heart valve systems .29
Annex H (informative) Examples of standards applicable to testing of materials and
components of heart valve systems .40
Annex I (informative) Raw and post-conditioning mechanical properties for support
structure materials .46
Annex J (informative) Corrosion assessment .48
Annex K (informative) Echocardiographic protocol .51
Bibliography .54
© ISO 2015 – All rights reserved iii

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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(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.
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 meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
Barriers to Trade (TBT) see the following URL: Foreword - Supplementary Information
The committee responsible for this document is ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This first edition of ISO 5840-1, together with ISO 5840-2 and ISO 5840-3, cancels and replaces
ISO 5840:2005, which has been technically revised.
ISO 5840 consists of the following parts, under the general title Cardiovascular implants — Cardiac valve
prostheses:
— Part 1: General requirements
— Part 2: Surgically implanted heart valve substitutes
— Part 3: Heart valve substitutes implanted by transcatheter techniques
iv © ISO 2015 – All rights reserved

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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(E)

Introduction
There is, as yet, no heart valve substitute which can be regarded as ideal.
The ISO 5840–series has been prepared by a group well aware of the issues associated with heart valve
substitutes and their development. In several areas, the provisions of the ISO 5840–series deliberately
have not been specified to encourage development and innovation. It does specify the types of tests,
test methods, and/or requirements for test apparatus and requires documentation of test methods
and results. The areas with which the ISO 5840–series are 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 clinician in choosing a heart valve substitute, and ensure that the device will
be presented at the operating table in 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, the ISO 5840–series also covers important
hydrodynamic and durability characteristics of heart valve substitutes. The ISO 5840–series does not
specify exact test methods for hydrodynamic and durability testing, but it offers guidelines for the test
apparatus.
The ISO 5840–series 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.
© ISO 2015 – All rights reserved v

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SIST EN ISO 5840-1:2015

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SIST EN ISO 5840-1:2015
INTERNATIONAL STANDARD ISO 5840-1:2015(E)
Cardiovascular implants — Cardiac valve prostheses —
Part 1:
General requirements
1 Scope
This part of ISO 5840 is applicable to heart valve substitutes intended for human implantation and
provides general requirements. Subsequent parts of the ISO 5840–series provide specific requirements.
This part of ISO 5840 is applicable to both newly developed and modified heart valve substitutes and
to the accessories, packaging, and labelling required for their implantation and for determining the
appropriate size of the heart valve substitute to be implanted.
This part of ISO 5840 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 preclinical in vivo evaluation and clinical evaluation of the finished
heart valve substitute.
This part of ISO 5840 defines operational conditions for heart valve substitutes.
This part of ISO 5840 excludes homografts.
NOTE A rationale for the provisions of this part of ISO 5840 is given in Annex A.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 5840-2, Cardiovascular implants — Cardiac valve prostheses —Part 2: Surgically implanted heart valve
substitutes
ISO 5840-3, Cardiovascular implants — Cardiac valve prostheses —Part 3: Heart valve substitutes
implanted by transcatheter techniques
ISO 11135, Sterilization of health-care products — Ethylene oxide — Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 11137 (all parts), Sterilization of health care products — Radiation
ISO 11607 (all parts), Packaging for terminally sterilized medical devices
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14160, Sterilization of health care products — Liquid chemical sterilizing agents for single-use medical
devices utilizing animal tissues and their derivatives — Requirements for characterization, development,
validation and routine control of a sterilization process for medical devices
ISO 14630:2012, Non-active surgical implants — General requirements
© ISO 2015 – All rights reserved 1

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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(E)

ISO 14937, 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, Medical devices — Application of risk management to medical devices
ISO 17665 (all parts), Sterilization of health care products — Moist heat
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 (3.28)
3.2
adverse event
AE
untoward medical occurrence in a study subject which does not necessarily have to have a causal
relationship with study treatment
Note 1 to entry: An AE can be an unfavourable and unintended sign (including an abnormal laboratory finding),
symptom, or disease, temporary or permanent, whether or not related to the prosthetic valve implantation or
procedure.
3.3
actuarial methods
statistical technique for calculating event rates over time
Note 1 to entry: Standard actuarial methods calculate the probability of freedom from events within pre-specified
intervals of time. When the intervals approach zero width, the methods are called Kaplan-Meier methods.
3.4
arterial end diastolic pressure
minimum value of the arterial pressure during diastole
3.5
arterial peak systolic pressure
maximum value of the arterial pressure during systole (3.63)
3.6
back pressure
differential pressure applied across the valve during the closed phase
3.7
body surface area
BSA
2
total surface area (m ) of the human body
Note 1 to entry: This can be calculated (Mosteller’s formula) as the square root of the product of the weight in kg
times the height in cm divided by 3 600 (see Reference [31]).
3.8
cardiac index
2 2
cardiac output (3.9) (CO, L/min) divided by the body surface area (3.7) (BSA, m ) with units L/min/m
3.9
cardiac output
CO
stroke volume (3.59) times heart rate
2 © ISO 2015 – All rights reserved

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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(E)

3.10
closing volume
portion of the regurgitant volume (3.48) that is associated with the dynamics of valve closure during a
single cycle (3.15)
Note 1 to entry: See Figure 1.
3.11
coating
thin-film material that is applied to an element of a heart valve system (3.29) to modify its physical or
chemical properties
3.12
compliance
relationship between change in diameter and change in pressure of a deformable tubular structure (e.g.
valve annulus, aorta, conduit) defined in this part of ISO 5840 as
()rr−×100
21
C=×100%
rp×−()p
12 1
where
C is the compliance in units of % radial change/100 mmHg;
p is the diastolic pressure, in mmHg;
1
p is the systolic pressure, in mmHg;
2
r is the inner radius at p , in millimetres;
1 1
r is the inner radius at p , in millimetres.
2 2
Note 1 to entry: Reference ISO 25539-1.
© ISO 2015 – All rights reserved 3

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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(E)

Key
X time
Y flowrate
1 closing volume
2 leakage volume
Figure 1 — Schematic representation of flow waveform and regurgitant volumes for one cycle
3.13
component-joining material
material such as a suture, adhesive, or welding compound used to assemble the components of a heart
valve system (3.29)
3.14
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 1 to entry: Cumulative incidence is also known as “actual” analysis.
3.15
cycle
one complete sequence in the action of a heart valve substitute (3.28) under pulsatile-flow conditions
3.16
cycle rate
number of complete cycles (3.15) per unit of time usually expressed as cycles per minute (cycles/min)
3.17
design verification
establishment by objective evidence that the design output meets the design input requirements
3.18
design validation
establishment by objective evidence that device specifications conform with user needs and intended
use(s) (3.31)
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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(E)

3.19
device embolization
dislodgement from the intended and documented original position to an unintended and non-
therapeutic location
3.20
device failure
inability of a device to perform its intended function sufficient to cause a hazard
3.21
device migration
detectable movement or displacement of the heart valve substitute (3.28) from its original position
within the implant position (3.30) and without device embolization (3.19)
3.22
effective orifice area
EOA
orifice area that has been derived from flow and pressure or velocity data
q
V
RMS
For in vitro testing, EOA is defined as:EOA=
Δp
51,6×
ρ
where
2
EOA is the Effective Orifice Area (cm );
is the root mean square forward flow (ml/s) during the positive differential pressure
q
V
RMS
period;
Δp is the mean pressure difference (measured during the positive differential pressure
period) (mmHg);
3
ρ is the density of the test fluid (g/cm ).
Note 1 to entry: See 3.53.
3.23
failure mode
mechanism of device failure (3.20)
Note 1 to entry: Support structure fracture, calcification, and prolapse are examples of failure modes.
3.24
flexible surgical heart valve substitute
surgical heart valve substitute (3.62) wherein the occluder (3.40) is flexible under physiological
conditions
Note 1 to entry: The orifice ring may or may not be flexible.
3.25
follow-up
continued assessment of patients who have received the heart valve substitute (3.28)
3.26
forward flow volume
volume of flow ejected through the heart valve substitute (3.28) in the forward direction during one
cycle (3.15)
© ISO 2015 – All rights reserved 5

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SIST EN ISO 5840-1:2015
ISO 5840-1:2015(E)

3.27
fracture
complete separation of any structural component of the heart valve substitute (3.28) that was previously
intact
3.28
heart valve substitute
device used to replace the function of a natural valve of the heart
3.29
heart valve system
implantable device, accessories (3.1), packaging, labelling, and instructions
3.30
implant site/implant position
intended location of heart valve substitute (3.28) implantation or deployment
3.31
intended use
use of a product or process in accordance with the specifications, instructions, and information
provided by the manufacturer
3.32
Kaplan-Meier methods
statistical approaches for calculating event rates over time when the actual dates of events for each
person in the population are known
3.33
leakage volume
portion of the regurgitant volume (3.48) which is associated with leakage during the closed phase of a
valve in a single cycle (3.15) and is the sum of the transvalvular leakage volume (3.66) and paravalvular
leakage volume (3.43)
Note 1 to entry: The point of separation between the closing and leakage volumes is obtained according to a
defined and stated criterion (the linear extrapolation shown in Figure 1 is just an example).
3.34
linearized rate
total number of events divided by the total time under evaluation
Note 1 to entry: Generally, the rate is expressed in terms of percent per patient year.
3.35
major bleeding
any episode of major internal or external bleeding that causes death, hospitalization, or permanent
injury (e.g. vision loss) or necessitates transfusion
3.36
major paravalvular leak
paravalvular leakage
...

SLOVENSKI STANDARD
oSIST prEN ISO 5840-1:2014
01-julij-2014
9VDGNLLPSODQWDWL]DVUFHLQRåLOMH3URWH]H]DVUþQR]DNORSNRGHO6SORãQH
]DKWHYH,62',6
Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements
(ISO/DIS 5840-1:2014)
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 1: Grundlegende
Anforderungen
Implants cardiovasculaires - Prothèses valvulaires - Partie 1: Exigences générales
(ISO/DIS 5840-1:2014)
Ta slovenski standard je istoveten z: prEN ISO 5840-1
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
oSIST prEN ISO 5840-1:2014 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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oSIST prEN ISO 5840-1:2014

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oSIST prEN ISO 5840-1:2014
DRAFT INTERNATIONAL STANDARD
ISO/DIS 5840-1
ISO/TC 150/SC 2 Secretariat: ANSI
Voting begins on: Voting terminates on:
2014-04-10 2014-07-10
Cardiovascular implants — Cardiac valve prostheses —
Part 1:
General requirements
Implants cardiovasculaires — Prothèses valvulaires —
Partie 1: Exigences générales
ICS: 11.040.40
ISO/CEN PARALLEL PROCESSING
This draft has been developed within the International Organization for
Standardization (ISO), and processed under the ISO lead mode of collaboration
as defined in the Vienna Agreement.
This draft is hereby submitted to the ISO member bodies and to the CEN member
bodies for a parallel five month enquiry.
Should this draft be accepted, a final draft, established on the basis of comments
received, will be submitted to a parallel two-month approval vote in ISO and
THIS DOCUMENT IS A DRAFT CIRCULATED
formal vote in CEN.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
To expedite distribution, this document is circulated as received from the
IN ADDITION TO THEIR EVALUATION AS
committee secretariat. ISO Central Secretariat work of editing and text
BEING ACCEPTABLE FOR INDUSTRIAL,
composition will be undertaken at publication stage.
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 5840-1:2014(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 2014

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oSIST prEN ISO 5840-1:2014
ISO/DIS 5840-1:2014(E)

Copyright notice
This ISO document is a Draft International Standard and is copyright-protected by ISO. Except as
permitted under the applicable laws of the user’s country, neither this ISO draft nor any extract
from it may be reproduced, stored in a retrieval system or transmitted in any form or by any means,
electronic, photocopying, recording or otherwise, without prior written permission being secured.
Requests for permission to reproduce should be addressed to either ISO at the address below or ISO’s
member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail [e-mail]
Web www.iso.org
Reproduction may be subject to royalty payments or a licensing agreement.
Violators may be prosecuted.
ii © ISO 2014 – All rights reserved

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oSIST prEN ISO 5840-1:2014

Contents
Foreword . v

Introduction . vi
1  Scope . 1
2  Normative references . 1
3  Terms and definitions . 2
4  Abbreviations . 11
5   Fundamental requirements . 12
6   Device description . 12
6.1   Intended use . 12
6.2  Design inputs . 12
6.2.1  Operational specifications . 12
6.2.2  Performance specifications . 142
6.2.3  Implant procedure . 12
6.2.4  Packaging, labeling, and sterilization . 13
6.3  Design outputs . 13
6.4  Design transfer (manufacturing verification/validation) . 14
6.5  Risk management . 15
7  Design verification testing and analysis / Design validation . 15
7.1  General requirements . 15
7.2  In vitro assessment . 15
7.3  Preclinical in vivo evaluation . 15
7.4  Clinical investigations . 15
Annex A (informative) Rationale for the provisions of this International Standard . 16
Annex B (normative)  Packaging . 19
Annex C (normative)  Product labels, instructions for use, and training . 20
Annex D (normative)  Sterilization . 23
Annex E (informative) In vitro test guidelines for paediatric devices . 24
Annex F (informative)  Statistical procedures when using in vitro performance
criteria . 29
Annex G (informative)  Examples and definitions of some physical and material
properties of heart valve systems . 30
Annex H (informative)  Examples of standards applicable to testing of materials
and components of heart valve systems . 40
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oSIST prEN ISO 5840-1:2014

Annex I (informative)  Raw and post-conditioning mechanical properties for
support structure materials . 45
Annex J (informative) Corrosion assessment . 47
Annex K (informative)Echocardiographic protocol . 50
Bibliography . 53


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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.
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 5840-1 was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee
SC 2, Cardiovascular implants and extracorporeal systems.

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oSIST prEN ISO 5840-1:2014

Introduction
There is, as yet, no heart valve substitute which can be regarded as ideal.
This International Standard has been prepared by a group well aware of the issues associated with heart valve
substitutes and their development. In several areas, the provisions of this International Standard deliberately
have not been specified to encourage 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 are 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 clinician in
choosing a heart valve substitute, and ensure that the device will be presented at the operating table in
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 Standard does not specify exact test methods for hydrodynamic and durability testing but it offers guidelines
for the test apparatus.
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.




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© ISO 2014 – All rights reserved
DRAFT INTERNATIONAL STANDARD  ISO/DIS 5840-1:201x
Cardiovascular implants—Cardiac valve prostheses—
Part 1: General requirements
1 Scope
1.1 This International Standard is applicable to heart valve substitutes intended for human implantation
and provides general requirements. Subsequent parts of this International Standard provide specific
requirements.
1.2 This International Standard is applicable to both newly developed and modified heart valve
substitutes and to the accessories, packaging, and labelling required for their implantation and for
determining the appropriate size of the 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 defines operational conditions for heart valve substitutes.
1.7 This International Standard excludes homografts.
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 11135-1:2007, Sterilization of health care products -- Ethylene oxide -- Part 1: Requirements for
development, validation and routine control of a sterilization process for medical devices

ISO 11135-2: Sterilization of health care products -- Ethylene oxide -- Part 2: Guidance on the application
of ISO 11135-1

ISO 11137-1, Sterilization of health care products — Radiation -- Part 1: Requirements for development,
validation and routine control of a sterilization process for medical devices
ISO 11137-2, Sterilization of health care products — Radiation — Part 2: Establishing the sterilization
dose
ISO 11137-3, Sterilization of health care products — Radiation — Part 3: Guidance on dosimetric aspects
ISO 11607-1, Packaging for terminally sterilized medical devices -- Part 1: Requirements for materials,
sterile barrier systems and packaging systems
ISO 11607-2, Packaging for terminally sterilized medical devices — Part 2: Validation requirements for
forming, sealing and assembly processes
ISO 14155:2011, Clinical investigation of medical devices for human subjects—Part 1: General
requirements

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oSIST prEN ISO 5840-1:2014

ISO 14160, Sterilization of single-use medical devices incorporating materials of animal origin—Validation
and routine control of sterilization by liquid chemical sterilants

ISO 14630:2012, 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 14971:2007, Medical devices—Application of risk management to medical devices
ISO 17665-1, Sterilization of health care products -- Moist heat -- Part 1: Requirements for the
development, validation and routine control of a sterilization process for medical devices

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
adverse event
AE
untoward medical occurrence in a study subject which does not necessarily have to have a causal
relationship with study treatment

NOTE 1 to entry: An AE can be an unfavorable and unintended sign (including an abnormal laboratory finding),
symptom, or disease, temporary or permanent, whether or not related to the prosthetic valve implantation or procedure.
3.3
actuarial methods
statistical technique for calculating event rates over time

NOTE 1 to entry: Standard actuarial methods calculate the probability of freedom from events within pre-specified
intervals of time. When the intervals approach zero width, the methods are called Kaplan-Meier methods.

3.4
arterial end diastolic pressure
minimum value of the arterial pressure during diastole

3.5
arterial peak systolic pressure
maximum value of the arterial pressure during systole

3.6
back pressure
differential pressure applied across the valve during the closed phase

3.7
body surface area
BSA
2
total surface area (m ) of the human body

NOTE 1 to entry: This can be calculated (Mosteller's formula) as the square root of the product of the weight in kg
times the height in cm divided by 3600. See Mosteller, RD.
3.8
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cardiac index
2 2
cardiac output (CO, lL/min) divided by the body surface area (BSA, m ), with units Ll/min/m

3.9 cardiac output
stroke volume times heart rate

3.10
closing volume
portion of the regurgitant volume that is associated with the dynamics of valve closure during a single
cycle

NOTE 1 to entry: See Figure 1.
3.11
coating
thin-film material that is applied to an element of a heart valve system to modify its physical or chemical
properties

3.12
compliance
relationship between change in diameter and change in pressure of a deformable tubular structure (e.g.,
valve annulus, aorta, conduit), defined in this document as:

(r r )100
2 1
C 100%
r (p  p )
1 2 1

where

C is the compliance in units of %radial change/100 mmHg
p is the diastolic pressure, in mmHg;
1
p is the systolic pressure, in mmHg;
2
 r is the inner radius at p , in millimeters;
1 1
r is the inner radius at p , in millimeters;
2 2

NOTE Reference ISO 25539-1.


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Figure 1 — Schematic representation of flow waveform and regurgitant volumes for one cycle
3.13
component-joining material
material, such as a suture, adhesive or welding compound, used to assemble the components of a heart
valve system

3.14
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 1 to entry: Cumulative incidence is also known as “actual” analysis.

3.15
cycle
one complete sequence in the action of a heart valve substitute under pulsatile-flow conditions

3.16
cycle rate
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number of complete cycles per unit of time, usually expressed as cycles per minute (cycles/min)

3.17
design verification
establishment by objective evidence that the design output meets the design input requirements

3.18
design validation
establishment by objective evidence that device specifications conform with user needs and intended
use(s)

3.19
device failure
inability of a device to perform its intended function sufficient to cause a hazard

3.20
device migration
detectable movement or displacement of the heart valve substitute from its original position within the
implant position, without device embolization

3.21
effective orifice area
EOA
orifice area that has been derived from flow and pressure or velocity data

For in-vitro testing, EOA is defined as:
q
v
RMS
EOA =
p
51,6 *

where
2
EOA is the Effective Orifice Area (cm );
q is the root mean square forward flow (ml/s) during the positive differential pressure period;
v
RMS
p is the mean pressure difference (measured during the positive differential pressure period) (mmHg);
3
  is the density of the test fluid (g/cm ).

3.22
prosthetic valve endocarditis
any infection involving a valve in which an operation has been performed, based on reoperation, autopsy
or the Duke Criteria for Endocarditis

NOTE 1 to entry: See Li et al (2000).

3.23
failure mode
mechanism of device failure

NOTE 1 to entry: Support structure fracture, calcification, and prolapse are examples of failure modes.

3.24
flexible surgical heart valve substitute
surgical heart valve substitute wherein the occluder is flexible under physiological conditions
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NOTE 1 to entry: The orifice ring may or may not be flexible.

3.25
follow-up
continued assessment of patients who have received the heart valve substitute

3.26
forward flow volume
volume of flow ejected through the heart valve substitute in the forward direction during one cycle

3.27
fracture
disruption, under the action of applied stress or strain, of any part of the heart valve substitute that was
previously intact

3.28
heart valve substitute
device used to replace the function of a natural valve of the heart

3.29
implant site/implant position
intended location of heart valve substitute implantation or deployment

3.30
intended use
use of a product or process in accordance with the specifications, instructions, and information provided
by the manufacturer

3.31
leakage volume
portion of the regurgitant volume which is associated with leakage during the closed phase of a valve in a
single cycle and is the sum of the transvalvular leakage volume and paravalvular leakage volume

NOTE 1 to entry: The point of separation between the closing and leakage volumes is obtained according to a defined
and stated criterion (the linear extrapolation shown in Figure 1 is just an example).

3.32
linearized rate
total number of events divided by the total time under evaluation

NOTE 1 to entry: Generally, the rate is expressed in terms of percent per patient year.

3.33
major bleeding
any episode of major internal or external bleeding that causes death, hospitalization, or permanent injury
(e.g. vision loss) or necessitates transfusion

3.34
mean arterial pressure
time-averaged arithmetic mean value of the arterial pressure during one cycle

3.35
mean pressure difference / mean pressure gradient
time-averaged arithmetic mean value of the pressure difference across a heart valve substitute during the
forward-flow phase of the cycle

3.36
nonstructural valve dysfunction
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abnormality extrinsic to the heart valve substitute that results in stenosis, regurgitation and/or haemolytic
anemia

3.37
occluder/leaflet
component that inhibits backflow

3.38
outflow tract profile height
maximum distance that the heart valve substitute extends axially into the outflow tract in the open or
closed position, whichever is greater, measured from the valve structure intended to mate with the top
(atrial or aortic/pulmonic side) of the patient's annulus

3.39
pannus
ingrowth of tissue onto the heart valve substitute which may interfere with normal functioning

3.40
paravalvular leakage volume
portion of the leakage volume that is associated with leakage around the closed heart valve substitute
during a single cycle

3.41
profile height
maximal axial dimension of a heart valve substitute in the open or closed position, whichever is greater

3.42
reference valve
heart valve substitute with a known clinical experience used for comparative preclinical and clinical
evaluations

NOTE 1 to entry: The reference valve should be legally marketed and approximate the test heart valve substitute in
type, configuration, and tissue annulus diameter; it may be an earlier model of the same valve, if it fulfils the necessary
conditions. The characteristics of the reference valve should be well documented with clinical data.

3.43
regurgitant fraction
regurgitant volume expressed as a percentage of the forward flow volume

3.44
regurgitant volume
volume of fluid that flows through a heart valve substitute in the reverse direction during one cycle and is
the sum of the closing volume and the leakage volume

NOTE 1 to entry: See Figure 1.

3.45
rigid surgical heart valve substitute
surgical heart valve substitute wherein the occluder(s) and orifice ring are non-flexible under physiological
conditions

3.46
risk
combination of the probability of occurrence of harm and the severity of that harm

NOTE 1 to entry: Adapted from ISO 14971

3.47
risk analysis
systematic use of available information to identify hazards and to estimate the associated risks
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NOTE 1 to entry: Adapted from ISO 14971.

3.48
risk assessment
overall process comprising a risk analysis and a risk evaluation

NOTE 1 to entry: Adapted from ISO 14971.

3.49
root mean square forward flow
RMS forward flow
square root of the integral of the volume flow rate waveform squared during the positive differential
pressure interval of the forward flow phase used to calculate EOA

NOTE 1 to entry: Defining the time interval for flow and pressure measurement as the positive pressure period of the
forward flow interval for EOA computation provides repeatable and consistent results for comparison to the Table 2
reference values.

NOTE 2 to entry:  This is calculated using the following equation:

t
2
2
q (t) dt
V

t
1

q 
V
RMS
t t
2 1


where

q
 is root mean square forward flow during the positive differential pressure period;
V
RMS
q (t) is instantaneous flow at time t;

V
t is time at start of positive differential pressure period;
1
t is time at end of positive differential pressure period.
2

q
NOTE 3 to entry: The rationale for use of is that the instantaneous pressure difference is proportional to the
V
RMS
square of instantaneous flow rate, and it is the mean pressure difference that is required.

NOTE 4 to entry: See Figure 2.
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Figure 2 — Schematic representation of the positive pressure period of an aortic forward flow
interval
3.50
safety
freedom from unacceptable risk

NOTE 1 to entry: Adapted from ISO 14971.

3.51
severity
measure of the possible consequences of a hazard

NOTE 1 to entry: Adapted from ISO 14971.

3.52
sterility assurance level
SAL
probability of a single viable microorganism occurring on an item after sterilization
6 3
NOTE 1 to entry: The term SAL takes a quantitative value, generally 10 or 10 . When applying this quantitative
6
value to assurance of sterility, an SAL of 10 has a lower value but provides a greater assurance of sterility than an
3
SAL of 10 .
NOTE 1 to entry: From ISO/TS 11139, definition 2.46.

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3.53
sterilization
validated process used to render a product free from viable microorganisms
NOTE 1 to entry: In a sterilization process, the rate of microbial inactivation is exponential and thus the survival of
a microorganism on an individual item can be expressed in terms of probability. While this probability can be reduced to
a very low number, it can never be reduced to zero.
NOTE 2 to entry: See 3.52.
NOTE 3 to entry: From ISO/TS 11139:2006.
3.54
structural valve deterioration
change in the function of a heart valve substitute resulting from an intrinsic abnormality that causes
stenosis or regurgitation

NOTE 1 to entry: This definition excludes infection, or thrombosis of the heart valve substitute. It includes intrinsic
changes such as wear, fatigue failure, stress fracture, occluder escape, suture line disruption of components of the
prosthesis, calcification, cavitation erosion, leaflet tear and stent creep.

3.55
support structure
component of a heart valve substitute that houses the occluder(s) (e.g. stent, frame, housing)

3.56
surgical heart valve substitute
heart valve substitute generally requiring direct visualization and cardiopulmonary bypass for implantation

3.57
systolic duration
systole
portion of cardiac cycle time corresponding to ventricular contraction

NOTE 1 to entry: See Figure 3.

3.58
tissue annulus diameter (TAD)
diameter in millimeters of the smallest flow area within the patient’s valve annulus

3.59
thromboembolism
any embolic event that occurs in the absence of infection after the immediate perioperative period.
Thromboembolism may be manifested by a neurological event or a noncerebral embolic event

3.60
transcatheter heart valve substitute
heart valve substitute implanted in a manner generally
...