SIST EN ISO 5840-2:2021
(Main)Cardiovascular implants - Cardiac valve prostheses - Part 2: Surgically implanted heart valve substitutes (ISO 5840-2:2021)
Cardiovascular implants - Cardiac valve prostheses - Part 2: Surgically implanted heart valve substitutes (ISO 5840-2:2021)
This document is applicable to heart valve substitutes intended for implantation in human hearts,
generally requiring cardiopulmonary bypass and generally with direct visualization. See Annex E for
examples of surgical heart valve substitutes and their components.
This document is applicable to both newly developed and modified surgical heart valve substitutes and
to the accessory devices, packaging, and labelling required for their implantation and for determining
the appropriate size of the surgical heart valve substitute to be implanted.
This document establishes an approach for verifying/validating the design and manufacture of a
surgical 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 surgical heart valve substitutes and of
their materials and components. The tests can also include those for pre-clinical in vivo evaluation and
clinical evaluation of the finished surgical heart valve substitute.
This document defines operational conditions and performance requirements for surgical heart valve
substitutes where adequate scientific and/or clinical evidence exists for their justification.
For some heart valve substitutes (e.g. sutureless), the requirements of both this document and
ISO 5840-3:2021 can be relevant and are considered as applicable to the specific device design and are
based on the results of the risk analysis.
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 2: Chirurgisch implantierter Herzklappenersatz (ISO 5840-2:2021)
Das Dokument ist auf Herzklappenersatz anwendbar, der für die Implantation im menschlichen Herzen vorgesehen ist, für die in der Regel ein kardiopulmonaler Bypass und direkte Sichtbarkeit erforderlich sind. Bezüglich Beispielen für chirurgisch implantierten Herzklappenersatz und dessen Bestandteilen siehe Anhang E.
Das Dokument ist sowohl auf neu entwickelten als auch auf veränderten chirurgisch implantierten Herzklappenersatz und seine Zubehörteile anwendbar und gilt für die Verpackung und die für die Implantation und die Ermittlung der geeigneten Größe des chirurgisch zu implantierenden Herzklappen¬ersatzes erforderliche Kennzeichnung.
Dieses Dokument legt eine Herangehensweise zur Verifizierung/Validierung des Designs und der Herstellung eines chirurgisch zu implantierenden Herzklappenersatzes auf der Grundlage des Risiko-managements fest. Die Auswahl der geeigneten Qualifikationsprüfungen und verfahren leitet sich aus der Risikobeurteilung ab. Zu diesen Prüfungen können solche zur Beurteilung der physikalischen, chemischen, biologischen und mechanischen Eigenschaften eines chirurgisch zu implantierenden Herzklappenersatzes und von dessen Werkstoffen und Bauteilen gehören. Diese Prüfungen können auch die vorklinische In vivo-Bewertung und die klinische Bewertung des fertigen chirurgisch implantierten Herzklappenersatzes einschließen.
Dieses Dokument legt Betriebsbedingungen für und Leistungsanforderungen an chirurgisch implantierten Herzklappenersatz fest, sofern angemessene wissenschaftliche und/oder klinische Nachweise für deren Begründung vorliegen.
Für einige Herzklappenprothesen (z. B. nahtlos) können die Anforderungen sowohl dieses Dokuments als auch von ISO 5840 3:2021 von Bedeutung sein und werden als für das spezifische Implantatdesign anwendbar angesehen und basieren auf den Ergebnissen der Risiko¬analyse.
Implants cardiovasculaires - Prothèses valvulaires - Partie 2: Prothèse valvulaires implantées chirurgicalement (ISO 5840-2:2021)
Le présent document s'applique aux prothèses valvulaires destinées à être implantées dans un cœur humain et nécessitant en général une circulation extra-corporelle et une visualisation directe. Voir des exemples de prothèses valvulaires implantées chirurgicalement et de leurs composants à l'Annexe E.
Le présent document s'applique à la fois aux prothèses valvulaires chirurgicales récemment mises au point et aux prothèses valvulaires chirurgicales 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 chirurgicale à implanter.
Le présent document établit une approche permettant de vérifier/valider la conception et la fabrication d'une prothèse valvulaire chirurgicale dans une optique de gestion du risque. La sélection des méthodes et des essais de qualification appropriés se fait à partir de l'appréciation du risque. Les essais peuvent être destinés à évaluer les propriétés physiques, chimiques, biologiques et mécaniques de prothèses valvulaires chirurgicales ainsi que celles de leurs matériaux et composants. Ces essais peuvent également englober les essais destinés à l'évaluation préclinique in vivo et à l'évaluation clinique des prothèses valvulaires chirurgicales à l'état fini.
Le présent document définit les conditions de fonctionnement et les exigences de performance relatives aux prothèses valvulaires chirurgicales lorsqu'il existe une preuve scientifique et/ou clinique adéquate pour les justifier.
Pour certaines prothèses valvulaires chirurgicales (par exemple, les prothèses sans suture), les exigences du présent document et de l'ISO 5840-3:2021 peuvent être pertinentes. Elles sont considérées comme applicables à la conception spécifique du dispositif, dans la mesure où elles s'appuient sur les résultats de l'analyse du risque.
Vsadki (implantati) za srce in ožilje - Proteze za srčno zaklopko - 2. del: Kirurško vsajeni (implantirani) nadomestki srčne zaklopke (ISO 5840-2:2021)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 5840-2:2021
01-marec-2021
Nadomešča:
SIST EN ISO 5840-2:2015
Vsadki (implantati) za srce in ožilje - Proteze za srčno zaklopko - 2. del: Kirurško
vsajeni (implantirani) nadomestki srčne zaklopke (ISO 5840-2:2021)
Cardiovascular implants - Cardiac valve prostheses - Part 2: Surgically implanted heart
valve substitutes (ISO 5840-2:2021)
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 2: Chirurgisch implantierter
Herzklappenersatz (ISO 5840-2:2021)
Implants cardiovasculaires - Prothèses valvulaires - Partie 2: Prothèse valvulaires
implantées chirurgicalement (ISO 5840-2:2021)
Ta slovenski standard je istoveten z: EN ISO 5840-2:2021
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
SIST EN ISO 5840-2:2021 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 5840-2:2021
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SIST EN ISO 5840-2:2021
EN ISO 5840-2
EUROPEAN STANDARD
NORME EUROPÉENNE
February 2021
EUROPÄISCHE NORM
ICS 11.040.40 Supersedes EN ISO 5840-2:2015
English Version
Cardiovascular implants - Cardiac valve prostheses - Part
2: Surgically implanted heart valve substitutes (ISO 5840-
2:2021)
Implants cardiovasculaires - Prothèses valvulaires - Herz- und Gefäßimplantate - Herzklappenprothesen -
Partie 2: Prothèse valvulaires implantées Teil 2: Chirurgisch implantierter Herzklappenersatz
chirurgicalement (ISO 5840-2:2021) (ISO 5840-2:2021)
This European Standard was approved by CEN on 21 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 5840-2:2021 E
worldwide for CEN national Members.
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SIST EN ISO 5840-2:2021
EN ISO 5840-2:2021 (E)
Contents Page
European foreword . 3
2
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SIST EN ISO 5840-2:2021
EN ISO 5840-2:2021 (E)
European foreword
This document (EN ISO 5840-2:2021) 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 5840-2:2015.
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 5840-2:2021 has been approved by CEN as EN ISO 5840-2:2021 without any
modification.
3
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SIST EN ISO 5840-2:2021
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SIST EN ISO 5840-2:2021
INTERNATIONAL ISO
STANDARD 5840-2
Second edition
2021-01
Cardiovascular implants — Cardiac
valve prostheses —
Part 2:
Surgically implanted heart valve
substitutes
Implants cardiovasculaires — Prothèses valvulaires —
Partie 2: Prothèse valvulaires implantées chirurgicalement
Reference number
ISO 5840-2:2021(E)
©
ISO 2021
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SIST EN ISO 5840-2:2021
ISO 5840-2:2021(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 5840-2:2021
ISO 5840-2:2021(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviations. 3
5 Fundamental requirements . 4
6 Device description . 4
6.1 General . 4
6.2 Intended use . 4
6.3 Design inputs . 4
6.3.1 Operational specifications . 4
6.3.2 Performance specifications . 4
6.3.3 Packaging, labelling, and sterilization . 5
6.4 Design outputs . 5
6.5 Design transfer (manufacturing verification/validation) . 5
6.6 Risk management . 6
7 Design verification and validation . 6
7.1 General requirements . 6
7.2 In vitro assessment . 6
7.2.1 General. 6
7.2.2 Test conditions, sample selection, and reporting requirements . 6
7.2.3 Material property assessment . 6
7.2.4 Hydrodynamic performance assessment . 6
7.2.5 Structural performance assessment . 7
7.2.6 Design- or procedure-specific testing. 8
7.2.7 Device MRI compatibility . 8
7.2.8 Simulated use. 8
7.2.9 Human factors/usability assessment . 8
7.2.10 Implant thrombogenic and haemolytic potential assessment . 8
7.3 Preclinical in vivo evaluation . 8
7.3.1 General. 8
7.3.2 Overall requirements . 8
7.3.3 Methods . 9
7.3.4 Test report .10
7.4 Clinical investigations .11
7.4.1 General.11
7.4.2 Study considerations .12
7.4.3 Study endpoints .13
7.4.4 Ethical considerations .14
7.4.5 Pivotal studies: Distribution of subjects and investigators .14
7.4.6 Statistical considerations including sample size and duration .15
7.4.7 Patient selection criteria .16
7.4.8 Valve thrombosis prevention .17
7.4.9 Clinical data requirements .17
Annex A (informative) Surgical heart valve substitute hazard analysis example .22
Annex B (informative) In vitro procedures for testing unstented or similar valves in
compliant chambers .24
Annex C (informative) Preclinical in vivo evaluation .26
Annex D (informative) Description of the surgical heart valve substitute and system.29
© ISO 2021 – All rights reserved iii
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SIST EN ISO 5840-2:2021
ISO 5840-2:2021(E)
Annex E (informative) Examples of components of some surgical heart valve substitutes
and systems .31
Annex F (informative) Guidelines for verification of hydrodynamic performance —
Pulsatile flow testing .37
Annex G (informative) Examples of design specific testing .41
Annex H (informative) Fatigue assessment .43
Annex I (normative) Methods of evaluating clinical data against objective performance criteria .45
Annex J (normative) Adverse event classification during clinical investigation .46
Bibliography .51
iv © ISO 2021 – All rights reserved
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SIST EN ISO 5840-2:2021
ISO 5840-2:2021(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 5840-2:2015), 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 of its 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 5840-2:2021
ISO 5840-2:2021(E)
Introduction
This document has been prepared for surgical heart valve substitutes with emphasis on providing
guidance for in vitro testing, preclinical in vivo and clinical evaluations, reporting of all in vitro,
preclinical in vivo, and clinical evaluations and labelling and packaging of the device. This process is
intended to clarify the required procedures prior to market release and to enable prompt identification
and management of any subsequent issues.
This document is used in conjunction with ISO 5840-1 and ISO 5840-3.
vi © ISO 2021 – All rights reserved
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SIST EN ISO 5840-2:2021
INTERNATIONAL STANDARD ISO 5840-2:2021(E)
Cardiovascular implants — Cardiac valve prostheses —
Part 2:
Surgically implanted heart valve substitutes
1 Scope
This document is applicable to heart valve substitutes intended for implantation in human hearts,
generally requiring cardiopulmonary bypass and generally with direct visualization. See Annex E for
examples of surgical heart valve substitutes and their components.
This document is applicable to both newly developed and modified surgical heart valve substitutes and
to the accessory devices, packaging, and labelling required for their implantation and for determining
the appropriate size of the surgical heart valve substitute to be implanted.
This document establishes an approach for verifying/validating the design and manufacture of a
surgical 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 surgical heart valve substitutes and of
their materials and components. The tests can also include those for pre-clinical in vivo evaluation and
clinical evaluation of the finished surgical heart valve substitute.
This document defines operational conditions and performance requirements for surgical heart valve
substitutes where adequate scientific and/or clinical evidence exists for their justification.
For some heart valve substitutes (e.g. sutureless), the requirements of both this document and
ISO 5840-3:2021 can be relevant and are considered as applicable to the specific device design and are
based on the results of the risk analysis.
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 5840-1:2021, Cardiovascular implants — Cardiac valve prostheses — Part 1: General requirements
ISO 5840-3, Cardiovascular implants — Cardiac valve prostheses — Part 3: Heart valve substitutes
implanted by transcatheter techniques
ISO 10993-2, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14630, Non-active surgical implants — General requirements
ISO 16061, Instrumentation for use in association with non-active surgical implants — General requirements
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 5840-1:2021 and the
following apply.
© ISO 2021 – All rights reserved 1
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SIST EN ISO 5840-2:2021
ISO 5840-2:2021(E)
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
acute assessment
intra-procedural and immediate post-procedural results used to assess in vivo safety and performance
Note 1 to entry: All animals entered into acute short-term assessment shall remain under general anaesthesia for
the duration of the study.
3.2
chronic assessment
long-term results following the procedure used to assess chronic in vivo safety and performance after
the animal has recovered from anaesthesia
Note 1 to entry: The endpoints and durations of these studies should be determined by risk analysis.
3.3
component-joining material
material such as a suture, adhesive, or welding compound used to assemble the components of a heart
valve system
[SOURCE: ISO 5840-1:2021, 3.31]
3.4
external sewing ring diameter
ESRD
outside diameter in millimetres of the sewing ring at the largest point
Note 1 to entry: See Figure 1.
Note 2 to entry: See also 3.5, 3.7 and 3.8.
3.5
prosthesis minimum internal diameter
numerical indication of the minimum diameter within a fully assembled
flexible surgical heart valve substitute and which is measured with a standard validated procedure,
taking the entire flow channel into consideration
Note 1 to entry: See Figure 1.
Note 2 to entry: See also 3.2 and 3.4.
3.6
prosthesis minimum internal diameter
measurement of the prosthesis minimum internal housing diameter
Note 1 to entry: See Figure 1.
Note 2 to entry: See also 3.2 and 3.4.
3.7
intra-annular
wholly or partially within the patient’s annulus
Note 1 to entry: See Figure 1.
Note 2 to entry: See also 3.4, 3.5 and 3.8.
2 © ISO 2021 – All rights reserved
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SIST EN ISO 5840-2:2021
ISO 5840-2:2021(E)
a) Aortic/pulmonic b) Aortic/pulmonic c) Mitral/tricuspid
intra-annular supra-annular intra-annular
Key
1 prosthesis minimum internal diameter
2 patient annulus diameter
3 external sewing ring diameter
Figure 1 — Designation of dimensions of surgical heart valve substitute sewing ring
configurations
3.8
supra-annulus
region wholly above the patient’s annulus
Note 1 to entry: See Figure 1.
Note 2 to entry: See also 3.4, 3.5, and 3.7.
3.9
patient annulus diameter
PAD
diameter in millimetres of the smallest flow area within the patient’s valve annulus
Note 1 to entry: See Figure 1.
3.10
valve size
designated valve size
manufacturer's designation of a surgical heart valve substitute which indicates the intended patient
annulus diameter
Note 1 to entry: The valve size is equivalent to the PAD (3.9).
Note 2 to entry: This takes into consideration the manufacturer's recommended implant position relative to the
annulus and the suture technique.
4 Abbreviations
For the purposes of this document, the following abbreviations apply.
AE adverse event
CIP clinical investigation plan
CRF case report form
© ISO 2021 – All rights reserved 3
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SIST EN ISO 5840-2:2021
ISO 5840-2:2021(E)
CT computed tomography
EOA effective orifice area
FEA finite element analysis
IFU instructions for use
LVOT left ventricular outflow tract
MRI magnetic resonance imaging
OPC objective performance criteria
PMCF post-market clinical follow-up
PVL paravalvular leak
RMS root mean square
SAE serious adverse event
TEE transoesophageal echo
TTE transthoracic echo
5 Fundamental requirements
Refer to ISO 5840-1:2021, Clause 5.
6 Device description
6.1 General
Refer to ISO 5840-1:2021, 6.1.
6.2 Intended use
Refer to ISO 5840-1:2021, 6.2.
6.3 Design inputs
6.3.1 Operational specifications
Refer to ISO 5840-1:2021, 6.3.1.
6.3.2 Performance specifications
6.3.2.1 General
Refer to ISO 5840-1:2021, 6.1 for general requirements.
6.3.2.2 Surgical heart valve substitute minimum performance requirements
Surgical heart valves shall meet the following minimum performance specifications:
— allow forward flow with acceptably small mean pressure difference;
4 © ISO 2021 – All rights reserved
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SIST EN ISO 5840-2:2021
ISO 5840-2:2021(E)
— prevent retrograde flow with acceptably small regurgitation;
— resist embolization;
— avoid haemolysis;
— resist thrombus formation;
— be biocompatible;
— be compatible with in vivo diagnostic techniques;
— be deliverable and implantable in the target population;
— be able to ensure effective fixation within the target implant site;
— have an acceptable noise level;
— have reproducible function;
— maintain structural and functional integrity during the expected lifetime of the device;
— maintain its functionality and sterility for a reasonable shelf life prior to implantation.
6.3.2.3 Accessories
The requirements of ISO 16061 for instruments used with surgical implants shall apply. Surgical heart
valve accessories shall mitigate the risk of the valve being inadvertently implanted upside down.
Examples of surgical valve accessories, including sizing tools and valve handles, are shown in Annex E.
6.3.2.4 Implant procedure
Refer to ISO 5840-1:2021, 6.3.3.
6.3.3 Packaging, labelling, and sterilization
Refer to ISO 5840-1:2021, 6.3.4.
In addition to the items specified in ISO 5840-1:2021, C.1.3, outer container labelling for the valve
implant shall include in diagrammatic and/or tabular form the following items:
— intended valve to be replaced;
— intended position in relation to the annulus;
— inflow internal orifice diameter;
— prosthesis minimum internal diameter;
— external sewing ring diameter (ESRD).
Annex D contains a list of terms that may be used in describing various valve models.
6.4 Design outputs
Refer to ISO 5840-1:2021, 6.4.
6.5 Design transfer (manufacturing verification/validation)
Refer to ISO 5840-1:2021, 6.5.
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SIST EN ISO 5840-2:2021
ISO 5840-2:2021(E)
6.6 Risk management
Refer to ISO 5840-1:2021, 6.6.
Annex A contains a list of potential hazards specific to surgical heart valve substitutes that can serve as
the basis for a risk analysis.
7 Design verification and validation
7.1 General requirements
In vitro assessment shall be used to mitigate the risks identified in the risk analysis. General
requirem
...
SLOVENSKI STANDARD
oSIST prEN ISO 5840-2:2019
01-marec-2019
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Cardiovascular implants - Cardiac valve prostheses - Part 2: Surgically implanted heart
valve substitutes (ISO/DIS 5840-2:2019)
Implants cardiovasculaires - Prothèses valvulaires - Partie 2: Prothèse valvulaires
implantées chirurgicalement (ISO/DIS 5840-2:2019)
Ta slovenski standard je istoveten z: prEN ISO 5840-2
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
oSIST prEN ISO 5840-2:2019 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 5840-2:2019
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oSIST prEN ISO 5840-2:2019
DRAFT INTERNATIONAL STANDARD
ISO/DIS 5840-2
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 2:
Surgically implanted heart valve substitutes
Implants cardiovasculaires — Prothèses valvulaires —
Partie 2: Prothèse valvulaires implantées chirurgicalement
ICS: 11.040.40
THIS DOCUMENT IS A DRAFT CIRCULATED
This document is circulated as received from the committee secretariat.
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
NOT BE REFERRED TO AS AN INTERNATIONAL
STANDARD UNTIL PUBLISHED AS SUCH.
IN ADDITION TO THEIR EVALUATION AS
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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 5840-2 cancels and replaces the first edition (ISO 5840-2:2015), 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
This part of ISO 5840 has been prepared for surgical heart valve substitutes with emphasis on
providing guidance for in vitro testing, preclinical in vivo and clinical evaluations, reporting of all in
vitro, preclinical in vivo, and clinical evaluations and labelling and packaging of the device. This
process is intended to clarify the required procedures prior to market release and to enable prompt
identification and management of any subsequent issues.
This part of ISO 5840 is to be used in conjunction with ISO 5840-1 and ISO 5840-3.
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Cardiovascular implants—Cardiac valve prostheses—Part 2:
Surgically implanted heart valve substitutes
1 Scope
This part of ISO 5840 is applicable to heart valve substitutes intended for implantation in human hearts,
generally requiring cardiopulmonary bypass and generally with direct visualization. See Annex E for
examples of surgical heart valve substitutes and their components.
This part of ISO 5840 is applicable to both newly developed and modified surgical heart valve substitutes
and to the accessory devices, packaging, and labelling required for their implantation and for determining
the appropriate size of the surgical heart valve substitute to be implanted.
This part of ISO 5840 outlines an approach for verifying/ validating the design and manufacture of a
surgical 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 surgical heart valve substitutes and of their materials
and components. The tests can also include those for pre-clinical in vivo evaluation and clinical evaluation
of the finished surgical heart valve substitute.
This part of ISO 5840 defines operational conditions and performance requirements for surgical heart
valve substitutes where adequate scientific and/or clinical evidence exists for their justification.
For novel surgical heart valve substitutes, e.g. sutureless, the requirements of both this International
Standard and ISO 5840-3 might be relevant and shall be considered as applicable to the specific device
design and shall be based on the results of the risk analysis.
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 5840-1, Cardiovascular implants — Cardiac valve prostheses — Part 1: General requirements
ISO 5840-3, Cardiovascular implants — Cardiac valve prostheses — Part 3: Heart valve substitutes
implanted by transcatheter techniques
ISO 10993-2, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14971, Medical devices — Application of risk management to medical devices
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 5840-1 and the following apply.
3.1
external sewing ring diameter
ESRD
the outside diameter in millimetres of the sewing ring at the largest point
3.2
internal orifice diameter
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IOD
numerical indication of the minimum diameter in millimetres within a surgical heart valve substitute
through which blood flows, excluding the hinge area for rigid bileaflet heart valve substitutes
Note 1 to entry: See Figure 1.
3.3
intra-annular sewing ring
sewing ring designed to secure the surgical heart valve wholly or mostly within the patient’s tissue
annulus
Note 1 to entry: See Figure 1.
Note 2 to entry: See also 3.1, 3.3, and 3.4.
Key
1 internal orifice diameter
2 tissue annulus diameter
3 external sewing ring diameter
Figure 1 — Designation of dimensions of surgical heart valve substitute sewing ring
configurations
3.4
prosthetic height (or valve projection)
• for an aortic valve, the largest height measured from the base of the valve to the tallest point of
the open valve
• for a mitral valve, the ventricular projection as measured from the ventricular side of the sewing
ring to the tallest point of the open valve
3.5
supra-annular sewing ring
sewing ring designed to secure the valve wholly above the patient’s tissue annulus
Note 1 to entry: See Figure 1.
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3.6
tissue annulus diameter
TAD
diameter in millimetres of the smallest flow area within the patient’s valve annulus
3.7
valve size
manufacturer's designation of a surgical heart valve substitute which indicates the tissue annulus
diameter (TAD in millimetres) of the patient into whom the surgical heart valve substitute is intended to
be implanted (i.e. TAD = designated valve size)
Note 1 to entry: This takes into consideration the manufacturer's recommended implant position relative to the
annulus and the suture technique.
4 Abbreviations
For the purposes of this document, the following abbreviations apply.
CT Computed Tomography
EOA Effective Orifice Area
FEA Finite Element Analysis
LVOT Left Ventricular Outflow Tract
MRI Magnetic Resonance Imaging
OPC Objective Performance Criteria
RMS Root Mean Square
TAD Tissue Annulus Diameter
TEE Transoesophageal Echo
TTE Transthoracic Echo
5 Fundamental requirements
Refer to ISO 5840-1.
6 Device description
6.1 General
Refer to ISO 5840-1.
6.2 Intended use
Refer to ISO 5840-1.
6.3 Design inputs
6.3.1 Operational specifications
Refer to ISO 5840-1.
6.3.2 Performance specifications
6.3.2.1 General
Refer to ISO 5840-1 for general requirements. Specific requirements are listed in 6.3.2.2.
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6.3.2.2 Surgical heart valve substitute
Specifications shall be defined with respect to at least the following performance characteristics:
— ability to allow forward flow with acceptably small mean pressure difference;
— ability to prevent retrograde flow with acceptably small regurgitation;
— ability to resist embolization;
— ability to avoid haemolysis;
— ability to resist thrombus formation;
— biocompatible;
— compatible with in vivo diagnostic techniques;
— deliverable and implantable in the target population;
— ability to ensure effective fixation within the target implant site;
— has an acceptable noise level;
— has reproducible function;
— maintains structural and functional integrity during the expected lifetime of the device;
— maintains its functionality and sterility for a reasonable shelf life prior to implantation.
6.3.3 Implant procedure
Refer to ISO 5840-1.
6.3.4 Packaging, labelling, and sterilization
Refer to ISO 5840-1.
In addition to the items specified in ISO 5840-1, Annex C, Section C.1.2, outer container labelling for the
valve implant shall include a diagram containing the following items:
- Tissue annular diameter (TAD)
- Internal orifice diameter (IOD)
- External suture ring diameter (ESRD)
- Prosthetic height
Annex D of this document contains a listing of terms that may be used in describing various valve models.
6.4 Design outputs
Refer to ISO 5840-1.
6.5 Design transfer (manufacturing verification/validation)
Refer to ISO 5840-1.
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6.6 Risk management
Refer to ISO 5840-1.
Annex A contains a list of potential hazards specific to surgical heart valve substitutes that can serve as
the basis for a risk analysis.
7 Design verification and validation
7.1 General requirements
In vitro assessment shall be used to mitigate the risks identified in the risk analysis. General requirements
that are applicable to all heart valve systems are provided in ISO 5840-1. Specific considerations for
surgical heart valve substitutes are provided in this part of ISO 5840.
7.2 In vitro assessment
7.2.1 General
Refer to ISO 5840-1.
7.2.2 Test conditions, sample selection, and reporting requirements
Refer to ISO 5840-1.
7.2.3 Material property assessment
Refer to ISO 5840-1.
7.2.4 Hydrodynamic performance assessment
Hydrodynamic testing shall be performed to provide information on the fluid mechanical performance of
the surgical heart valve substitute. Annex I of ISO 5840-1 provides guidelines for conducting and
reporting steady hydrodynamic tests. Guidelines for conducting and reporting of pulsatile hydrodynamic
tests is provided in Annex F. For pulsatile flow testing, the performance of the pulse duplicator shall be
characterized by means of testing a commercially available reference valve(s) in the valve position(s) to
be evaluated (e.g. aortic and/or mitral). The measurement accuracy and repeatability of the test
system(s) shall be evaluated and documented. The hydrodynamic waveforms produced by the pulse
duplicator shall reasonably simulate physiological conditions. Representative waveforms used to
generate hydrodynamic test results shall be documented in the test report. Reference [11] provides
characteristics of reasonable aortic and mitral waveforms.
Tests shall be carried out on at least three surgical heart valve substitutes of each size and on at least one
reference valve of each of the smallest, medium, and largest sizes. A larger sample size may be required
to ensure adequate representation of the expected variability in the manufacture of devices.
The in vitro test results shall meet or exceed the minimum performance requirements provided in Table
1 and Table 2, which are given as a function of valve size. The minimum performance requirements
correspond to the following pulsatile-flow conditions: beat rate = 70 cycles/min, simulated cardiac
output = 5,0 l/min, and systolic duration = 35 %, at normotensive pressure conditions. These pulsatile
flow conditions are based on a healthy normal adult and might not be applicable for paediatric device
evaluation (see Annex E in ISO 5840-1 for paediatric parameters). The minimum performance
requirements are based on values in the published scientific literature. The values in Table 1 and Table 2
are applicable to new or modified heart valve substitutes which have not been clinically proven or
evaluated under previous versions of ISO 5840.
For pulmonary and tricuspid heart valve substitutes, minimum performance requirements are not
provided; however, the manufacturer shall justify the acceptability of hydrodynamic performance of the
devices.
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Additional hydrodynamic characterization testing shall be conducted over a range of test conditions as
described in Annex F, Sections F.2.3.2 and F.2.3.3. This testing is for characterization purposes only
without corresponding minimum performance requirements.
Table 1 — Minimum device performance requirements, Aortic
Valve size (mm)
Parameter
17 19 21 23 25 27 29 31
2
EOA (cm ) greater than or equal to 0,70 0,85 1,05 1,25 1,45 1,70 1,95 2,25
Total Regurgitant Fraction (% of
forward flow volume) less than or 10 10 10 10 15 15 20 20
equal to
Table 2—Minimum device performance requirements, Mitral
Valve size (mm)
Parameter
23 25 27 29 31 33
2
EOA (cm ) greater than or equal
1,05 1,25 1,45 1,65 1,90 2,15
to
Total Regurgitant Fraction (% of
forward flow volume) less than 15 15 15 20 20 20
or equal to
The total regurgitant fraction shall include closing volume, transvalvular leakage volume, and
paravalvular leakage volume.
7.2.5 Structural performance assessment
7.2.5.1 General
An assessment of the ability of the surgical heart valve substitute to withstand the loads and/or
deformations to which it will be subjected shall be performed in order to evaluate the risks associated
with potential structural failure modes.
7.2.5.1.1 Implant durability assessment
See ISO 5840-1.
7.2.5.2 Device structural component fatigue assessment
See ISO 5840-1 and Annex H.
7.2.5.3 Component corrosion assessment
See ISO 5840-1.
7.2.5.4 Cavitation (rigid valves)
An assessment of the potential for cavitation as indicated by the formation of vapor bubbles during valve
closure shall be considered for rigid valves. Assessment of cavitation damage shall be performed by a
detailed examination of study valves used in the preclinical in vivo study and simulated long term in vitro
study (i.e. durability testing). The in vitro cavitation assessment shall be performed by characterization
of the smallest and largest valve sizes in terms of any observed damage and the extent of damage
compared to the appropriate reference valves.
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7.2.6 Design- or procedure-specific testing
7.2.6.1 General
See Annex G for examples of design specific or procedure specific testing to be considered. The
manufacturer shall define all applicable requirements based on the results of the risk assessment for the
specific device design. For example, novel surgically implanted heart valve substitutes (e.g. sutureless)
may require additional testing as compared to traditional surgically implanted valves, and the
requirements of both this International Standard and ISO 5840-3 might be relevant and shall be
considered. See Annex E for examples of novel surgically implanted heart valve substitutes that may
require additional evaluation.
7.2.6.2 Visibility
The ability to visualize the implanted device using the manufacturer’s recommended imaging modality
[e.g. fluoroscopy, MRI, computed tomography (CT), echocardiography] shall be evaluated.
7.2.7 Device MRI compatibility
Refer to ISO 5840-1.
7.2.8 Simulated use
See ISO 5840-1.
The ability to permit safe, consistent, and accurate implantation of the surgical heart valve substitute
within the intended implant position shall be evaluated using a model that simulates the intended use
conditions. This assessment will include all elements of the surgical heart valve substitute.
The model shall consider anatomical variation in intended patient population with respect to intended
implant site as well as physiologic factors (e.g. temperature effects, pulsatile flow). In the case where
device anchoring relies on specific interactions with the native anatomy (e.g. annulus, aortic root), testing
shall be included in the simulated use evaluation. Justification for critical parameters of the simulated use
model shall be provided. Potential hazards associated with inaccurate valve implantation and resulting
effects on valve performance and unintended anatomical interactions (e.g. coronary occlusion, anterior
mitral impingement, LVOT obstruction, systolic anterior motion) shall be documented within the risk
assessment.
7.2.9 Human factors/usability assessment
See ISO 5840-1.
7.2.10 Implant thrombogenic and haemolytic potential assessment
See ISO 5840-1.
7.3 Preclinical in vivo evaluation
7.3.1 Overall requirements
A preclinical in vivo test programme shall be conducted in order to address the surgical heart valve
substitute safety and performance. The preclinical programme design shall be based on risk management
assessment. This programme may involve the use of different species and implant durations to address
the key issues identified in the risk assessment.
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For minor design modifications to clinically well-documented surgical heart valve substitutes, the
manufacturer shall justify omission of animal experimental evaluation. Preclinical studies are
recommended for design changes of a marketed device that may affect the safety and effectiveness (e.g.
novel blood-contacting materials, changes that alter the flow characteristics or haemodynamics, and
changes that affect the mechanical loading on the valve).
The preclinical in vivo evaluation shall:
a) reflect the hemodynamic performance of the surgical heart valve substitute as assessed in vitro;
b) assess the surgical handling characteristics of the test surgical heart valve substitute and its
accessories (if any);
c) assess the biological reaction to the surgical heart valve substitute. Consideration should be given
but not limited to the following items, as relevant to the specific surgical heart valve substitute under
evaluation:
1) healing characteristics (pannus formation, tissue overgrowth);
2) hemolysis;
3) thrombus formation;
4) embolization of material from the heart valve substitute;
5) biological response (e.g. inflammation, rejection, etc.);
6) calcification (flexible valves);
7) acoustic characteristics (rigid valves), if the manufacturer is making specific acoustic claims;
8) structural and/or non-structural dysfunction;
9) cavitation (rigid valves);
d) mimic, as closely as possible, the condition of the finished product as intended for clinical use,
including exposure to the maximum number of recommended sterilization cycles;
e) evaluate the test surgical heart valve substitute in all positions for which it is intended (aortic, mitral,
etc.);
f) subject comparably sized reference surgical heart valve substitutes to identical test conditions as the
test surgical heart valve substitute;
g) mimic, as closely as possible, the implantation technique for the placement of both the test and the
reference surgical heart valve substitutes (e.g. suture technique and orientation);
h) be performed by appropriately experienced and knowledgeable test laboratories;
i) address animal welfare in accordance with the principles given in ISO 10993-2.
7.3.2 Methods
Guidance on the conduct of in vivo preclinical evaluation and a series of tests which can be used to address
the relevant issues are given in Annex C. The intent of these studies is to mimic as closely as possible the
clinical use and haemodynamic performance of the surgical heart valve substitute. It is recognized that
complications arising after valve implantation can be attributed to the implanted valve as well as the
environment into which it is implanted or the interaction between the two. Therefore, adverse clinical
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events arising during or after valve implantation shall be carefully analysed and interpreted in order to
identify the cause of the adverse event to the extent possible.
The investigator should seek to control as many variables as possible within each study arm (e.g. species,
gender, and age). The test surgical heart valve substitutes shall be assessed in a long term setting in
anatomical positions for which it is intended to be used clinically. Animals suffering from perioperative
complications not related to the heart valve substitute may be excluded from the group of study animals,
but information about them shall be reported.
The number of animals used for implantation of test and control surgical heart valve substitutes and
study endpoints shall be justified fully for each test based on the risk analysis.
For all studies, the specified duration of the observation period of the animals shall be justified according
to the parameter(s) under investigation. Any pre-clinical investigation with a designated endpoint of less
than 140 days requires a thorough justification with rationale as to why a longer survival period was not
attempted. A minimum duration of 90 days is suitable for minor modifications to existing devices, such
as investigations of healing. New devices (e.g. new design or novel blood-contacting materials) require
an extended duration of the observation period (not less than 140 days).
A macroscopic, radiographic, and histological post-mortem examination shall be performed, focusing on
device integrity and device-related pathology. The data shall include information from all animals that
have been entered into the study.
The assessment shall provide at least the following:
a) any detectable pathological consequences involving the surgical heart valve substitute and/or the
major organs, including but not limited to: post-implantation changes in shape or structural
components, thrombo-embolic phenomena, pannus formation, and inflammatory responses;
b) any macro- or microscopic or radiographic detectable structural alterations in the surgical heart
valve substitute (e.g. damage, support structure fracture, material degeneration, changes in shape or
dimensions);
c) serial blood analyses performed pre-operatively, at appropriately justified intervals during the
observation period, and at termination to assess haemolysis, abnormalities in hematology and
clinical chemistry parameters;
d) implantation characteristics, including but not limited to ease of use, handling characteristics, and
sizing technique;
2
e) haemodynamic performance over a range of cardiac indices (e.g. 2,5 to 6,0 L/min/m );
f) any paravalvular leakage (PVL);
g) adverse clinical events, (e.g. myocardial infarction, significant cardiac arrhythmias, infection);
h) any other system or procedure related complication or events.
7.3.3 Test report
The test laboratory shall produce the test report, which shall include a summary assessment of the data
generated during the course of the investigation. The test report shall include the complete study
protocol. All data generated from the preclinical in vivo evaluation must be incorporated into a
comprehensive test report. The report should include the results generated by tests described in Annex C.
The test report shall include the following:
a) identification of each valve used (product description, serial number, and other appropriate valve
identification);
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b) detailed description of the animal model used and the rationale and justification for its use. The pre-
procedural assessment of each animal shall include documentation of health status as well as gender,
weight, and age of the animal;
c) description of the operative procedure, including implant technique, test surgical heart valve
substitute orientation, valve position, and operative complications;
d) description of the pre-procedural and post-procedural clinical course of each animal including,
clinical observations, medication(s), and interventions used to treat adverse clinical events. Describe
anticoagulation or antiplatelet drug and regimen used as well as therapeutic level monitoring
methods;
e) any significant deviations from the protocol or amendments to the protocol and their significance;
f) names of the investigators and their institutions along with information about the implanting
personnel and the laboratory’s experience with surgical heart valve substitute implantation and
animal care;
g) interpretation of data, including a comparison of the results between test and reference animals, and
a recommendation relative
...
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