SIST EN ISO 5840-1:2021
(Main)Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements (ISO 5840-1:2021)
Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements (ISO 5840-1:2021)
This document is applicable to heart valve substitutes intended for implantation and provides general
requirements. Subsequent parts of the ISO 5840 series provide specific requirements.
This document is applicable to 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 the heart valve substitute to be implanted.
ISO 5840-1 outlines an approach for verifying/validating 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 can include those to assess the physical, chemical,
biological, and mechanical properties of heart valve substitutes and of their materials and components.
The tests can also include those for preclinical in vivo evaluation and clinical evaluation of the finished
heart valve substitute.
ISO 5840-1 defines operational conditions for heart valve substitutes.
ISO 5840-1 furthermore defines terms that are also applicable to ISO 5840-2 and ISO 5840-3.
ISO 5840-1 does not provide requirements specific to homografts, tissue engineered heart valves
(e.g. valves intended to regenerate in vivo), and heart valve substitutes designed for implantation in
circulatory support devices. Some of the provisions of ISO 5840-1 can be applied to valves made from
human tissue that is rendered non-viable.
NOTE A rationale for the provisions of ISO 5840-1 is given in Annex A.
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 1: Allgemeine Anforderungen (ISO 5840-1:2021)
Dieses Dokument ist auf Herzklappenersatz anwendbar, der für die Implantation in den Körper vorgesehen ist, und enthält allgemeine Anforderungen. Spezifische Anforderungen werden in den anderen Teilen der Normenreihe ISO 5840 festgelegt.
Dieses Dokument gilt für neu entwickelten und veränderten Herzklappenersatz; die Zubehörteile, Verpackung und Kennzeichnung, die für die Implantation erforderlich sind; und die Bestimmung der geeigneten Größe des zu implantierenden Herzklappenersatzes.
ISO 5840-1 umreißt eine Herangehensweise zur Überprüfung/Validierung des Designs und der Herstellung eines Herzklappenersatzes auf der Grundlage des Risikomanagements. Die Auswahl der geeigneten Qualifi¬kationsprüfungen und verfahren leitet sich aus der Risikobeurteilung ab. Zu diesen Prüfungen können solche zur Beurteilung der physikalischen, chemischen, biologischen und mechanischen Eigenschaften eines Herzklappenersatzes und von dessen Werkstoffen und Bauteilen gehören. Diese Prüfungen können auch die vorklinische In vivo und die klinische Bewertung des fertigen Herzklappenersatzes einschließen.
ISO 5840-1 legt Betriebsbedingungen für Herzklappenersatz fest.
ISO 5840 1 definiert darüber hinaus Begriffe, die auch für ISO 5840 2 und ISO 5840 3 gelten.
ISO 5840-1 stellt keine Anforderungen, die für Homografte, gewebetechnologisch hergestellte Herzklappen (z. B. Herzklappen, die In vivo regenerieren sollen) und Herzklappenersatz, der für die Implantation in Kreislaufunterstützungssystemen ausgelegt ist, spezifisch sind. Einige der Regelungen von ISO 5840-1 können auf aus abgetötetem menschlichen Gewebe hergestellten Klappen angewendet werden.
ANMERKUNG Eine Begründung für die Festlegungen von ISO 5840-1 wird in Anhang A gegeben.
Implants cardiovasculaires - Prothèses valvulaires - Partie 1: Exigences générales (ISO 5840-1:2021)
Le présent document s'applique aux prothèses valvulaires destinées à une implantation chez l'homme et établit des exigences générales. Les exigences spécifiques figurent dans les parties qui succèdent à la présente partie de l'ISO 5840.
Le présent document s'applique aux prothèses valvulaires récemment mises au point et aux prothèses valvulaires modifiées, ainsi qu'aux dispositifs auxiliaires, à l'emballage et à l'étiquetage exigés pour leur implantation. Il s'applique également à la détermination de la taille appropriée de la prothèse valvulaire à implanter.
L'ISO 5840-1 présente une approche pour la vérification/validation de 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. Des essais peuvent être destinés à évaluer les propriétés physiques, chimiques, biologiques et mécaniques de prothèses valvulaires ainsi que celles 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.
L'ISO 5840-1 définit les conditions de fonctionnement des prothèses valvulaires.
En outre, l'ISO 5840-1 définit les termes qui sont aussi applicable à l'ISO 5840-2 et l'ISO 5840-3.
L'ISO 5840-1 ne contient pas d'exigences spécifiques aux homogreffes, aux valves cardiaques issues de l'ingénierie tissulaire (par exemple, valves conçues pour se régénérer in vivo), ni aux prothèses valvulaires conçues pour une implantation dans des dispositifs d'assistance circulatoire. Certaines dispositions de l'ISO 5840-1 peuvent s'appliquer à des valves réalisées à partir de tissus humains rendus non viables.
NOTE Une justification des dispositions de l'ISO 5840-1 est donnée à l'Annexe A.
Vsadki (implantati) za srce in ožilje - Proteze za srčno zaklopko - 1. del: Splošne zahteve (ISO 5840-1:2021)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 5840-1:2021
01-marec-2021
Nadomešča:
SIST EN ISO 5840-1:2015
Vsadki (implantati) za srce in ožilje - Proteze za srčno zaklopko - 1. del: Splošne
zahteve (ISO 5840-1:2021)
Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements (ISO
5840-1:2021)
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 1: Allgemeine Anforderungen
(ISO 5840-1:2021)
Implants cardiovasculaires - Prothèses valvulaires - Partie 1: Exigences générales (ISO
5840-1:2021)
Ta slovenski standard je istoveten z: EN ISO 5840-1:2021
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
SIST EN ISO 5840-1:2021 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 5840-1:2021
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SIST EN ISO 5840-1:2021
EN ISO 5840-1
EUROPEAN STANDARD
NORME EUROPÉENNE
February 2021
EUROPÄISCHE NORM
ICS 11.040.40 Supersedes EN ISO 5840-1:2015
English Version
Cardiovascular implants - Cardiac valve prostheses - Part
1: General requirements (ISO 5840-1:2021)
Implants cardiovasculaires - Prothèses valvulaires - Herz- und Gefäßimplantate - Herzklappenprothesen -
Partie 1: Exigences générales (ISO 5840-1:2021) Teil 1: Allgemeine Anforderungen (ISO 5840-1:2021)
This European Standard was approved by CEN on 22 September 2020.
CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, 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: Rue de la Science 23, B-1040 Brussels
© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 5840-1:2021 E
worldwide for CEN national Members.
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SIST EN ISO 5840-1:2021
EN ISO 5840-1:2021 (E)
Contents Page
European foreword . 3
2
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SIST EN ISO 5840-1:2021
EN ISO 5840-1:2021 (E)
European foreword
This document (EN ISO 5840-1:2021) 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 August 2021, and conflicting national standards shall
be withdrawn at the latest by August 2021.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 5840-1:2015.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 5840-1:2021 has been approved by CEN as EN ISO 5840-1:2021 without any
modification.
3
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SIST EN ISO 5840-1:2021
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SIST EN ISO 5840-1:2021
INTERNATIONAL ISO
STANDARD 5840-1
Second edition
2021-01
Cardiovascular implants — Cardiac
valve prostheses —
Part 1:
General requirements
Implants cardiovasculaires — Prothèses valvulaires —
Partie 1: Exigences générales
Reference number
ISO 5840-1:2021(E)
©
ISO 2021
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021
All rights reserved. Unless otherwise specified, or required in the context of its implementation, 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
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviations.15
5 Fundamental requirements .15
6 Device description .16
6.1 General .16
6.2 Intended use .16
6.3 Design inputs .16
6.3.1 Operational specifications .16
6.3.2 Performance specifications .17
6.3.3 Implant procedure.17
6.3.4 Packaging, labelling, and sterilization .17
6.4 Design outputs .18
6.5 Design transfer (manufacturing verification/validation) .18
6.6 Risk management .18
7 Design verification and validation .18
7.1 General requirements .18
7.2 In vitro assessment .18
7.2.1 General.18
7.2.2 Test conditions, sample selection and reporting requirements .19
7.2.3 Material property assessment .20
7.2.4 Hydrodynamic performance assessment .21
7.2.5 Structural performance assessment .21
7.2.6 Design- or procedure-specific testing.23
7.2.7 Device MRI compatibility .23
7.2.8 Simulated use.23
7.2.9 Human factors/usability assessment .23
7.2.10 Implant thrombogenic and haemolytic potential assessment .23
7.3 Preclinical in vivo evaluation .24
7.4 Clinical investigations .24
Annex A (informative) Rationale for the provisions of ISO 5840-1 .25
Annex B (normative) Packaging .28
Annex C (normative) Product labels, instructions for use, and training .29
Annex D (normative) Sterilization .32
Annex E (normative) In vitro test guidelines for paediatric devices .33
Annex F (informative) Corrosion assessment .37
Annex G (informative) Echocardiographic protocol .40
Annex H (informative) Assessment of implant thrombogenic and haemolytic potential .42
Annex I (informative) Guidelines for hydrodynamic performance characterization by
steady flow testing .53
Annex J (normative) Durability testing.60
Annex K (informative) Fatigue assessment .68
Annex L (normative) Clinical investigation endpoints for heart valve replacement devices .73
© ISO 2021 – All rights reserved iii
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(E)
Bibliography .76
iv © ISO 2021 – All rights reserved
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(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 of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see www .iso .org/
iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee
SC 2, Cardiovascular implants and extracorporeal systems, in collaboration with the European Committee
for Standardization (CEN) Technical Committee CEN/TC 285, Non-active surgical implants, in accordance
with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).
This second edition cancels and replaces the first edition (ISO 5840-1:2015), which has been technically
revised.
The main changes compared to the previous edition are as follows: the engineering and clinical
requirements in the ISO 5840 series have been updated to current specifications and integrated and
harmonized across all parts.
A list of all parts in the ISO 5840 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/ members .html.
© ISO 2021 – All rights reserved v
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(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,
provides guidance for test methods and test apparatuses and requires documentation of test methods
and results. The areas with which the ISO 5840 series are concerned are those which 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
is presented in a convenient form. Emphasis has been placed on specifying types of in vitro testing,
preclinical in vivo and clinical evaluations, reporting of all in vitro, preclinical in vivo, and clinical
evaluations, and 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 and systems required for their implantation.
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 intended to be revised, updated, and/or amended as knowledge and techniques
in heart valve substitute technology improve.
This document is used in conjunction with ISO 5840-2 and ISO 5840-3.
vi © ISO 2021 – All rights reserved
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SIST EN ISO 5840-1:2021
INTERNATIONAL STANDARD ISO 5840-1:2021(E)
Cardiovascular implants — Cardiac valve prostheses —
Part 1:
General requirements
1 Scope
This document is applicable to heart valve substitutes intended for implantation and provides general
requirements. Subsequent parts of the ISO 5840 series provide specific requirements.
This document is applicable to 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 the heart valve substitute to be implanted.
ISO 5840-1 outlines an approach for verifying/validating 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 can include those to assess the physical, chemical,
biological, and mechanical properties of heart valve substitutes and of their materials and components.
The tests can also include those for preclinical in vivo evaluation and clinical evaluation of the finished
heart valve substitute.
ISO 5840-1 defines operational conditions for heart valve substitutes.
ISO 5840-1 furthermore defines terms that are also applicable to ISO 5840-2 and ISO 5840-3.
ISO 5840-1 does not provide requirements specific to homografts, tissue engineered heart valves
(e.g. valves intended to regenerate in vivo), and heart valve substitutes designed for implantation in
circulatory support devices. Some of the provisions of ISO 5840-1 can be applied to valves made from
human tissue that is rendered non-viable.
NOTE A rationale for the provisions of ISO 5840-1 is given in Annex A.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements 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 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 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
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 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
© ISO 2021 – All rights reserved 1
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(E)
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, Non-active surgical implants — General requirements
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 15223-1, Symbols to be used with medical device labels, labelling and information to be supplied —
Part 1: General requirements
ISO 22442 (all parts), Medical devices utilizing animal tissues and their derivatives
IEC 62366 (all parts), Medical Devices — Application of usability engineering to medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
accessory
device-specific tool that is required to assist in the implantation of the heart valve substitute (3.30)
3.2
adverse event
AE
untoward medical occurrence in a study subject which does not necessarily 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 heart valve substitute (3.30) or
implantation procedure.
3.3
area-derived valve diameter
D
A
calculated valve diameter based on area (A) of the device [i.e. a “D-Shaped” transcatheter mitral valve
implantation (TMVI) device; refer to Figure 1]: D = 4 A/π
A
Note 1 to entry: This approach is typically used for labelling the sizes of TMVI devices where valves are designed
for a noncircular geometry.
2 © ISO 2021 – All rights reserved
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(E)
Key
1 area of valve
D = 4 A/π
A
D = area-derived diameter
A
Figure 1 — Area-derived valve diameter for a non-circular device
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 (3.68)
3.6
back pressure
differential pressure 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
and the height in cm divided by 3 600 (see Reference [26]).
3.8
cardiac output
CO
stroke volume (3.64) times heart rate
3.9
closing volume
portion of the regurgitant volume (3.49) that is associated with the dynamics of valve closure during a
single cycle (3.13)
Note 1 to entry: See Figure 2.
Note 2 to entry: The volume of flow occurring between end of systole (3.23) and start of leakage (3.59) for aortic
and pulmonary positions; between end of diastole (3.21) and start of leakage for mitral and tricuspid positions.
3.10
coating
thin-film material that is applied to an element of a heart valve system (3.31) to modify its surface
physical or chemical properties
© ISO 2021 – All rights reserved 3
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(E)
3.11
compliance
relationship between change in diameter and change in pressure of a deformable tubular structure (e.g.
aorta, conduit) defined in ISO 5840 (all parts) 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: See ISO 25539-1.
Key
X time 1 closing volume
Y flowrate 2 leakage volume
NOTE The total regurgitant volume is the sum of the closing volume and the leakage volume.
Figure 2 — Schematic representation of flow waveform, regurgitant volumes, and end of
closure determination for one cycle
4 © ISO 2021 – All rights reserved
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(E)
3.12
control valve
heart valve substitute for preclinical and clinical evaluations of similar design and constructed of
similar material as the investigational device
Note 1 to entry: The control valve should have a known clinical history.
3.13
cycle
complete sequence in the action of a heart valve substitute (3.30) under pulsatile-flow conditions
3.14
cycle rate
beat rate
number of complete cycles (3.13) per unit of time usually expressed as cycles per minute (cycles/min or
beats/min [bpm])
3.15
design verification
establishment by objective evidence that the design output meets the design input requirements
3.16
design validation
establishment by objective evidence that device specifications conform with user needs and intended
use(s) (3.33)
3.17
device embolization
dislodgement from the intended and documented original position to an unintended and non-
therapeutic location
3.18
device failure
inability of a device to perform its intended function
3.19
diastole
diastolic duration
portion of cardiac cycle time corresponding to ventricular filling
Note 1 to entry: Refer to Figure 3 and Figure 4.
3.20
effective orifice area
EOA
orifice area that has been derived from flow and pressure or velocity data
Note 1 to entry: For in vitro testing, EOA is defined as:
q
v
RMS
A =
eo
Δp
51,6×
ρ
where
2
A is the effective orifice area (cm );
eo
is the root mean square forward flow (3.54) (ml/s) during the positive differential pressure peri-
q
V
RMS
od (3.44);
is the mean pressure difference (measured during the positive differential pressure period)
Δp
(mmHg);
© ISO 2021 – All rights reserved 5
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SIST EN ISO 5840-1:2021
ISO 5840-1:2021(E)
3
ρ is the density of the test fluid (g/cm ).
3.21
end of diastole
ED
end of forward flow (zero crossing of flow to negative) for mitral and tricuspid positions
Note 1 to entry: ED corresponds to the start of valve closure (SC) for the mitral and tricuspid positions. Refer to
Figure 3 and Figure 4.
3.22
end of positive differential pressure
EPDP
second crossing of aortic and left ventricular pressure waveforms for aortic position; second crossing
of pulmonary and right ventricular pressure waveforms for pulmonary position; second crossing of
atrial and ventricular pressure waveforms for mitral and tricuspid position
Note 1 to entry: Refer to Figure 3 and Figure 4.
3.23
end of systole
ES
end of forward flow (zero crossing
...
SLOVENSKI STANDARD
oSIST prEN ISO 5840-1:2019
01-marec-2019
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Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements
(ISO/DIS 5840-1:2019)
Implants cardiovasculaires - Prothèses valvulaires - Partie 1: Exigences générales
(ISO/DIS 5840-1:2019)
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 5840-1:2019 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 5840-1:2019
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oSIST prEN ISO 5840-1:2019
DRAFT INTERNATIONAL STANDARD
ISO/DIS 5840-1
ISO/TC 150/SC 2 Secretariat: ANSI
Voting begins on: Voting terminates on:
2019-01-14 2019-04-08
Cardiovascular implants — Cardiac valve prostheses —
Part 1:
General requirements
Implants cardiovasculaires — Prothèses valvulaires —
Partie 1: Exigences générales
ICS: 11.040.40
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
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WHICH REFERENCE MAY BE MADE IN
Reference number
NATIONAL REGULATIONS.
ISO/DIS 5840-1:2019(E)
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NOTIFICATION OF ANY RELEVANT PATENT
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©
PROVIDE SUPPORTING DOCUMENTATION. ISO 2019
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oSIST prEN ISO 5840-1:2019
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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.
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 second edition of ISO 5840-1 cancels and replaces the first edition (ISO 5840-1:2015), 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
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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, provides guidance for test methods and test apparatuses 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 in convenient form.
Emphasis has been placed on specifying types of in vitro testing, preclinical in vivo and clinical
evaluations, reporting of all in vitro, preclinical in vivo, and clinical evaluations, and 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 and systems
required for their implantation. 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 intended to be revised, updated, and/or amended as knowledge and
techniques in heart valve substitute technology improve.
This part of ISO 5840 is to be used in conjunction with ISO 5840 parts 2 and 3.
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Cardiovascular implants—Cardiac valve prostheses—
Part 1: General requirements
1 Scope
This part of ISO 5840 is applicable to heart valve substitutes intended for implantation and
provides general requirements. Subsequent parts of the ISO 5840 series provide specific
requirements.
ISO 5840 is applicable to: newly developed and modified heart valve substitutes; the
accessory devices, packaging, and labelling required for their implantation; and for
determining the appropriate size of the heart valve substitute to be implanted.
ISO 5840 outlines an approach for verifying/validating 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 can also include those for
preclinical in vivo evaluation and clinical evaluation of the finished heart valve substitute.
ISO 5840 defines operational conditions for heart valve substitutes.
ISO 5840 does not provide requirements specific to homografts, tissue engineered heart
valves (e.g. valves intended to regenerate in vivo), and heart valve substitutes designed for
implantation in circulatory support devices.
NOTE: A rationale for the provisions 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 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing
within a risk management process
ISO 10993-4, Biological evaluation of medical devices – Part 4: Selection of tests for
interactions with blood
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
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ISO 13485, Medical devices — Quality management systems — Requirements for
regulatory purposes
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, Non-active surgical implants — General requirements
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/IEC 17025, General requirements for the competence of testing and calibration
laboratories
ISO 176651, Sterilization of health care products — Moist heat — Part 1: Requirements for
the development, validation and routine control of a sterilization process for medical devices
ISO 22442-1, Medical devices utilizing animal tissues and their derivatives — Part 1:
Application of risk management
ISO 22442-2, Medical devices utilizing animal tissues and their derivatives — Part 2:
Controls on sourcing, collection and handling
ISO 22442-3, Medical devices utilizing animal tissues and their derivatives — Part 3:
Validation of the elimination and/or inactivation of viruses and transmissible spongiform
encephalopathy (TSE) agents
ISO/TR 22442-4, Medical devices utilizing animal tissues and their derivatives — Part 4:
Principles for elimination and/or inactivation of transmissible spongiform encephalopathy
(TSE) agents and validation assays for those processes
IEC 62366, Medical Devices – Application of usability engineering to medical devices
ASTM F1830 – 97, Standard practice for selection of blood for in vitro evaluation of blood
pumps
ASTM F2052, Standard Test Method for Measurement of Magnetically Induced Displacement
Force on Medical Devices in the Magnetic Resonance Environment
ASTM F2119, Standard Test Method for Evaluation of MR Image Artifacts from Passive
Implants
ASTM F2182, Standard Test Method for Measurement of Radio Frequency Induced Heating
On or Near Passive Implants During Magnetic Resonance Imaging
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ASTM F2213, Standard Test Method for Measurement of Magnetically Induced Torque on
Medical Devices in the Magnetic Resonance Environment
ASTM F2503, Standard Practice for Marking Medical Devices and Other Items for Safety in
the Magnetic Resonance Environment
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 (3.33)
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 (3.73)
3.6
back pressure
differential pressure 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 [7]).
3.8
cardiac index
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2
cardiac output (3.9) (L/min) divided by the body surface area (3.7) (m ) with units
2
L/min/m
3.9
cardiac output
CO
stroke volume (3.69) times heart rate
3.10
closing volume
portion of the regurgitant volume (3.53) 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 (3.34) 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. aorta, conduit) defined in ISO 5840 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 millimetres;
1 1
r is the inner radius at p , in millimetres.
2 2
Note 1 to entry: Reference ISO 25539-1 [3].
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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 (3.34)
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 (3.33) 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
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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) (3.36)
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
3.21
device migration
detectable movement or displacement of the heart valve substitute (3.33) from its original
position within the implant position (3.35) 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
For in vitro testing, EOA is defined as:
q
v
RMS
EOA=
p
51,6
where
2
EOA is the Effective Orifice Area (cm );
is the root mean square forward flow (3.58) (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 ).
3.23
end of diastole
ED
end of forward flow (zero crossing of flow to negative) for mitral and tricuspid positions
3.24
end of leakage
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EL
Start of systole (SS) for aortic and pulmonary positions; start of diastole (SD) for mitral
and tricuspid positions.
3.25
end of positive differential pressure
EPDP
First crossing of aortic and left ventricular waveforms for aortic position; first crossing of
pulmonary and right ventricular waveforms for pulmonary position; first crossing of
atrial and ventricular waveforms for mitral and tricuspid position.
3.26
end of systole
ES
End of forward flow (zero crossing of flow to negative) for aortic and pulmonary positions
3.27
end of closure
EC
If no zero crossing of flow, use a linear extrapolation of highest slope of flow; if zero
crossing, use the first zero crossing.
3.28
failure mode
mechanism of device failure (3.20)
Note 1 to entry: Support structure fracture, calcification, and prolapse are examples of failure modes.
3.29
flexible surgical heart valve substitute
surgical heart valve substitute (3.72) wherein the occluder (3.45) is flexible under
physiological conditions (e.g. bioprostheses)
Note 1 to entry: The orifice ring may or may not be flexible.
3.30
follow-up
continued assessment of patients who have received the heart valve substitute (3.33)
3.31
forward flow volume
volume of flow ejected through the heart valve substitute (3.33) in the forward direction
during one cycle (3.15)
3.32
fracture
complete separation of any structural component of the heart valve substitute (3.33) that
was previously intact
3.33
heart valve substitute
device used to replace the function of a natural valve of the heart
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3.34
heart valve system
implantable device, accessories (3.1), packaging, labelling, and instructions
3.35
implant site/implant position
intended location of heart valve substitute (3.33) implantation or deployment
3.36
intended use
use of a product or process in accordance with the specifications, instructions, and
information provided by the manufacturer
3.37
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
3.38
leakage volume
portion of the regurgitant volume (3.53) 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
(3.76) and paravalvular leakage volume (3.48)
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).
3.39
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.
3.40
major bleeding
any episode of major internal or external bleeding that causes death, hospitalization, or
permanent injury (e.g. vision loss) or necessitates transfusion
3.41
major paravalvular leak
paravalvular leakage leading to or causing any of the following: death or reintervention;
heart failure requiring additional medication; moderate or severe regurgitation; prosthesis
“rocking” on investigation even in the apparent absence of symptoms; or haemolytic
anaemia
3.42
mean arterial pressure
time-averaged arithmetic mean value of the arterial pressure during one cycle (3.15)
3.43
mean pressure difference/mean pressure gradient
time-averaged arithmetic mean value of the pressure difference across a heart valve
substitute (3.33) during the positive differential pressure period of the cycle (3.15)
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3.44
nonstructural valve dysfunction
abnormality extrinsic to the heart valve substitute (3.33) that results in stenosis,
regurgitation, and/or haemolytic anaemia
3.45
occluder/leaflet
component that inhibits backflow
3.46
outflow tract profile height
maximum distance that the heart valve substitute (3.33) extends axially into the outflow
tract in the open or closed position, whichever is greater
3.47
pannus
ingrowth of tissue onto the heart valve substitute (3.33) which can interfere with normal
functioning
3.48
paravalvular leakage volume
portion of the leakage volume (3.38) that is associated with leakage around the closed heart
valve substitute during a single cycle (3.15)
3.49
profile height
maximal axial dimension of a heart valve substitute (3.33) in the open or closed position,
whichever is greater
3.50
prosthetic valve endocarditis
any infection involving a prosthetic valve based on reoperation, autopsy, or the Duke
Criteria for endocarditis
Note 1 to entry: See Reference [15]
3.51
reference valve
heart valve substitute (3.33) with a known clinical experience used for comparative
preclinical and clinical evaluations
3.52
regurgitant fraction
regurgitant volume (3.53) expressed as a percentage of the forward flow volume (3.31)
3.53
regurgitant volume
volume of fluid that flows through a heart valve substitute (3.33) in the reverse direction
during one cycle (3.15) and is the sum of the closing volume (3.10) and the leakage volume
(3.38)
NOTE 1 to entry: Clinically, it may only be possible to measure the leakage volume, and may not
include the closing volume.
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NOTE 2 to entry: See Figure 1.
3.54
rigid surgical heart valve substitute
surgical heart valve substitute (3.72) wherein the occluder(s) (3.45) and orifice ring are non-
flexible under physiological conditions (e.g. mechanical heart valves)
3.55
risk
combination of the probability of occurrence of harm and the severity (3.60) of that harm
[SOURCE: ISO 14971:2012, 2.16]
3.56
risk analysis
systematic use of available information to identify hazards and to estimate the associated
risks (3.55)
[SOURCE: ISO 14971:2012, 2.17]
3.57
risk assessment
overall process comprising a risk analysis (3.56) and a risk evaluation
[SOURCE: ISO 14971:2012, 2.18]
3.58
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 minimum device performance requirements.
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
is root mean square forward flow during the positive differential pressure period;
q
V
RMS
is instantaneous flow at time (t);
qt()
V
t is time at start of positive differential pressure period (3.64);
1
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t is time at end of positive differential pressure period (3.25).
2
Note 3 to entry: The rationale for use of q is that the instantaneous pressure difference is
V
RMS
proportional to the square of instantaneous flow rate and it is the mean pressure difference (3.43)
that is required.
Note 4 to entry: See Figure 2 for representative aortic and mitral flow and pressure waveforms from
in vitro testing. See Figure 3 for representative pulmonary and tricuspid flow and pressure
waveforms from in vitro testing.
(a) Aortic valve
(b) Mitral valve
1 aortic pressure
2 left ventricular pressure
NOTE Dashed vertical lines correspond to the flow trace
3 left atrial pressure
Solid vertical lines correspond to the pressure traces.
4 aortic flow rate
5 mitral flow rate
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Figure 2 Schematic representation of aortic and mitral flow and pressure
waveforms versus time from in vitro testing
(a) Pulmonary valve
(b) Tricuspid valve
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1 pulmonary pressure
2 right ventricular pressure
NOTE Dashed vertical lines correspond to the flow trace
3 right atrial pressure
Solid vertical lines correspond to the pressure traces.
4 pulmonary flow rate
5 tricuspid flow rate
Figure 3 Schematic representation of pulmonary and tricuspid flow and pressure
waveforms versus time from in vitro testing
3.59
safety
freedom from unacceptable risk
[SOURCE: ISO 14971:2012, 2.24]
3.60
severity
measure of the possible consequences of a hazard
[SOURCE: ISO 14971:2012, 2.25]
3.61
simulated cardiac output
for in vitro testing, simulated cardiac output rather than cardiac output is used where:
simulated cardiac output = forward flow volume X beat rate (tolerance +/- 0.1 L)
3.62
Start of diastole
SD
beginning of forward flow (zero crossing of flow to positive), for mitral and tricuspid
positions.
3.63
Start of leakage
SL
end of closure
3.64
Start of positive differential pressure
SPDP
first crossing of aortic and left ventricular waveforms for aortic position; first crossing of
pulmonary and right ventricular waveforms for pulmonary position; first crossing of
atrial and ventricular waveforms for mitral and tricuspid position.
3.65
Start of systole
SS
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beginning of forward flow (zero crossing of flow to positive), for aortic and pulmonary
positions.
3.66
Start of valve closure
SC
end of systole (ES), for aortic and pulmonary positions; End of diastole (ED) for mitral and
tricuspid positions.
3.67
sterility assurance level
SAL
probability of a single viable microorganism occurring on an item after sterilization (3.68)
−6 −3
Note 1 to entry: The term SAL takes a quantitative value, generally 10 or 10 . When applying this
−6
quantitative value to assurance of sterility, an SAL of 10 has a lower value, but provides a greater
−3
assurance of sterility than an SAL of 10 .
[SOURCE: ISO/TS 11139:2006, 2.46] [4]
3.68
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 3.67.
[SOURCE: ISO/TS 11139:2006]
...
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