EN ISO 5840-2:2015

SLOVENSKI STANDARD
01-december-2015
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Cardiovascular implants - Cardiac valve prostheses - Part 2: Surgically implanted heart
valve substitutes (ISO 5840-2:2015)
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 2: Chirurgisch implantierter
Herzklappenersatz (ISO 5840-2:2015)
Implants cardiovasculaires - Prothèses valvulaires - Partie 2: Prothèse valvulaires
implantées chirurgicalement (ISO 5840-2:2015)
Ta slovenski standard je istoveten z: EN ISO 5840-2:2015
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 5840-2
EUROPEAN STANDARD
NORME EUROPÉENNE
September 2015
EUROPÄISCHE NORM
ICS 11.040.40 Supersedes EN ISO 5840:2009
English Version
Cardiovascular implants - Cardiac valve prostheses - Part
2: Surgically implanted heart valve substitutes (ISO 5840-
2:2015)
Implants cardiovasculaires - Prothèses valvulaires - Herz- und Gefäßimplantate - Herzklappenprothesen -
Partie 2: Prothèse valvulaires implantées Teil 2: Chirurgisch implantierter Herzklappenersatz
chirurgicalement (ISO 5840-2:2015) (ISO 5840-2:2015)
This European Standard was approved by CEN on 24 July 2015.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 5840-2:2015 E
worldwide for CEN national Members.

Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices . 4

European foreword
This document (EN ISO 5840-2:2015) has been prepared by Technical Committee ISO/TC 150
“Implants for surgery” in collaboration with Technical Committee CEN/TC 285 “Non-active surgical
implants” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by March 2016, and conflicting national standards shall
be withdrawn at the latest by September 2018.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
This document supersedes EN ISO 5840:2009.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).
For relationship with EU Directive(s), see informative Annex ZA, which is an integral part of this
document.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 5840-2:2015 has been approved by CEN as EN ISO 5840-2:2015 without any
modification.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices
This European Standard has been prepared under a mandate given to CEN by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has
been implemented as a national standard in at least one Member State, compliance with the clauses of
this standard given in Table ZA.1 confers, within the limits of the scope of this standard, a presumption
of conformity with the corresponding Essential Requirements of that Directive and associated EFTA
regulations.
Table ZA.1 — Correspondence between this European Standard
and Directive 93/42/EEC on medical devices
Clause(s)/sub-clause(s) Essential Requirements (ERs) Qualifying remarks/Notes
of this European Standard of Directive 93/42/EEC
Clause 5, 6.1, 6.2.1, 6.2.2, 6.4 7.1
6.2, 6.2.3, 6.4, 7.2.2.2 7.2
6.2, 6.4 7.3
6.2, 6.4, 6.5, 7.2.2.2 7.5
6.2.2, 6.4, 6.5 7.6
6.2, 6.4, 6.5 8.1
6.5, 7.2.2.2 8.2
6.2.3 8.3
6.2.3 8.4
6.4 8.5
6.2.3 8.6
6.2.3 8.7
6.3, 6.2.3 9.1
6.2.1, 6.2.2, 6.4, 6.5 9.2
6.2.3, 6.3 13
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this standard.
INTERNATIONAL ISO
STANDARD 5840-2
First edition
2015-09-15
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 5840-2:2015(E)
©
ISO 2015
ISO 5840-2:2015(E)
© ISO 2015, Published in Switzerland
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
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Tel. +41 22 749 01 11
Fax +41 22 749 09 47
copyright@iso.org
www.iso.org
ii © ISO 2015 – All rights reserved

ISO 5840-2:2015(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviations. 4
5 Fundamental requirements . 4
6 Device description . 5
6.1 Intended use . 5
6.2 Design inputs . 5
6.2.1 Operational specifications . 5
6.2.2 Performance specifications . 5
6.2.3 Packaging, labelling, and sterilization . 6
6.3 Design outputs . 6
6.3.1 General. 6
6.4 Design transfer (manufacturing qualification) . 6
6.5 Risk management . 6
7 Design verification testing and analysis/design validation . 6
7.1 General requirements . 6
7.2 In vitro assessment . 7
7.2.1 Test conditions, sample selection, and reporting requirements . 7
7.2.2 Material property assessment . 8
7.2.3 Hydrodynamic performance assessment . 8
7.2.4 Structural performance assessment .10
7.2.5 Device MRI safety .11
7.2.6 Additional implant design evaluation requirements .11
7.2.7 Design specific testing .12
7.2.8 Simulated use.12
7.2.9 Human factors/usability assessment .12
7.3 Preclinical in vivo evaluation .12
7.3.1 Overall requirements .12
7.3.2 Methods .13
7.3.3 Test report .14
7.4 Clinical investigation .15
7.4.1 General.15
7.4.2 Statistical considerations .15
7.4.3 Distribution of subjects and investigators .15
7.4.4 Sample size .15
7.4.5 Entry criteria .16
7.4.6 Duration of the study .16
7.4.7 Clinical data requirements .16
7.4.8 Clinical investigation report .18
Annex A (informative) Heart valve substitute hazards, associated failure modes, and
evaluation methods .20
Annex B (informative) In vitro procedures for testing unstented or similar valves in
compliant chambers .23
Annex C (informative) Preclinical in vivo evaluation .25
Annex D (informative) Description of the surgical heart valve substitute.28
Annex E (informative) Examples of components of some surgical heart valve substitutes .30
ISO 5840-2:2015(E)
Annex F (informative) Guidelines for verification of hydrodynamic performance .34
Annex G (informative) Durability testing .43
Annex H (informative) Examples of design specific testing .45
Annex I (informative) Fatigue assessment .47
Annex J (normative) Methods of evaluating clinical data .53
Bibliography .54
iv © ISO 2015 – All rights reserved

ISO 5840-2:2015(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This first edition of ISO 5840-2, together with ISO 5840-1 and ISO 5840-3, cancels and replaces
ISO 5840:2005, which has been technically revised.
ISO 5840 consists of the following parts, under the general title Cardiovascular implants — Cardiac
valve prostheses:
— Part 1: General requirements
— Part 2: Surgically implanted heart valve substitutes
— Part 3: Heart valve substitutes implanted by transcatheter techniques
ISO 5840-2:2015(E)
Introduction
This part of ISO 5840 has been prepared for surgical heart valve substitutes with emphasis 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 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.
vi © ISO 2015 – All rights reserved

INTERNATIONAL STANDARD ISO 5840-2:2015(E)
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.
This part of ISO 5840 is applicable to both newly developed and modified surgical heart valve substitutes
and to the accessories, 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 qualifying 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 may 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 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.
This part of ISO 5840 excludes heart valve substitutes designed for implantation in artificial hearts or
heart assist devices.
This part of ISO 5840 excludes homografts.
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 5840-1:2015, Cardiovascular implants and extracorporeal systems — Cardiac valve prostheses —
Part 1: General requirements
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
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 14971, Medical devices — Application of risk management to medical devices
ISO 16061, Instrumentation for use in association with non-active surgical implants – General requirements
ISO 5840-2:2015(E)
ISO/IEC 17025:2005, General requirements for the competence of testing and calibration laboratories
ISO 22442 (all parts), Medical devices utilizing animal tissues and their derivatives
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
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 given in ISO 5840-1 and the
following apply.
3.1
cycle rate
number of complete cycles per unit of time, usually expressed as cycles per minute (cycles/min)
3.2
internal orifice diameter
numerical indication of the minimum diameter within a surgical heart valve substitute through
which blood flows
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 3.2, 3.10, and 3.12.
2 © ISO 2015 – All rights reserved

ISO 5840-2:2015(E)
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
major bleeding
any episode of major internal or external bleeding that causes death, hospitalization, or permanent
injury (e.g. vision loss) or necessitates transfusion
3.5
major paravalvular leak
paravalvular leakage leading to death or re-intervention, or causing heart failure requiring additional
medication, or causing moderate or severe regurgitation or prosthesis ‘rocking’ on investigation even
in the apparent absence of symptoms, or causing hemolytic anemia
3.6
nonstructural valve dysfunction
abnormality extrinsic to the heart valve substitute that results in stenosis, regurgitation, and/or
haemolytic anemia
3.7
prosthetic valve endocarditis
any infection involving a valve in which an operation has been performed, based on reoperation,
autopsy or the Duke Criteria for Endocarditis
Note 1 to entry: See Reference [16].
3.8
structural valve deterioration
change in the function of a heart valve substitute resulting from an intrinsic abnormality that causes
stenosis or regurgitation
Note 1 to entry: This definition excludes infection or thrombosis of the heart valve substitute. It includes intrinsic
changes such as wear, fatigue failure, stress fracture, occluder escape, suture line disruption of components of
the prosthesis, calcification, cavitation erosion, leaflet tear, and stent creep.
ISO 5840-2:2015(E)
3.9
support structure
component of a heart valve substitute that houses the occluder(s)
EXAMPLE Stent, frame, housing.
3.10
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.
3.11
thromboembolism
any embolic event that occurs in the absence of infection after the immediate perioperative period and
may be manifested by a neurological event or a noncerebral embolic event
3.12
tissue annulus diameter
TAD
diameter in millimetres of the smallest flow area within the patient’s valve annulus
3.13
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.
3.14
valve thrombosis
any thrombus not caused by infection attached to or near an operated valve that occluded part of the
blood flow path, interferes with valve function, or is sufficiently large to warrant treatment
Note 1 to entry: See Reference [14].
4 Abbreviations
For the purposes of this document, the following abbreviations apply.
EOA Effective Orifice Area
CFD Computational Fluid Dynamics
FEA Finite Element Analysis
IFU Instructions For Use
OPC Objective Performance Criteria
5 Fundamental requirements
The manufacturer shall determine, at all stages of the product life cycle, the acceptability of the product
for clinical use.
4 © ISO 2015 – All rights reserved

ISO 5840-2:2015(E)
6 Device description
6.1 Intended use
The manufacturer shall identify the physiological condition(s) to be treated, the intended patient
population, potential adverse events, and intended claims.
6.2 Design inputs
6.2.1 Operational specifications
The manufacturer shall define the operational specifications for the device, including the principles of
operation, expected device lifetime, shelf life, shipping/storage limits, and the physiological environment
in which it is intended to function. The manufacturer shall carefully define all relevant dimensional
parameters that will be required to accurately select the size of device to be implanted. ISO 5840-1:2015,
Table 1 and Table 2 define the expected physiological parameters of the intended adult patient population
for surgical heart valve substitutes for both normal and pathological patient conditions.
NOTE See the paediatric annex of ISO 5840-1:2015, Annex E.
6.2.2 Performance specifications
6.2.2.1 The manufacturer shall establish (i.e. define, document, and implement) the clinical
performance requirements of the device and the corresponding device performance specifications for
the intended use and device claims. The following list of desired clinical and device-based performance
characteristics describes a safe and effective surgical heart valve substitute.
NOTE For novel devices, portions of ISO 5840-3 can be applicable
6.2.2.2 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 resist 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.
ISO 5840-2:2015(E)
6.2.3 Packaging, labelling, and sterilization
The surgical heart valve substitute and accessories shall meet the requirements for packaging, labelling,
and sterilization contained within ISO 5840-1:2015, Annexes B, C, and D, respectively.
6.3 Design outputs
6.3.1 General
The manufacturer shall establish (i.e. define, document, and implement) a complete specification of the
surgical heart valve substitute system, which includes component and assembly-level specifications,
accessories, packaging, and labelling.
Annex E contains a listing of components and terms that may be used in describing various valve types.
6.4 Design transfer (manufacturing qualification)
6.4.1 The manufacturer shall generate a manufacturing flowchart identifying the manufacturing
process operations and inspection steps. The input of all components and important manufacturing
materials shall be indicated on the flowchart.
6.4.2 As part of the risk management process, the manufacturer shall establish the control measures
and process conditions necessary to ensure that the device is safe and suitable for its intended use. The
risk management file shall identify and justify the verification activities necessary to demonstrate the
acceptability of the process ranges chosen.
6.4.3 The manufacturer shall establish the adequacy of full-scale manufacturing by validation of the
manufacturing process. The manufacturer shall document the results of the validation of all special
processes and the validation of all process software.
NOTE See ISO 13485.
6.5 Risk management
The manufacturer shall define and implement a risk management program in accordance with ISO 14971.
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 testing and analysis/design validation
7.1 General requirements
The manufacturer shall perform verification testing in order to demonstrate that the device
specifications result in a surgical heart valve substitute system that meets the design specifications
(design output meets design input). The manufacturer shall establish those tests relating to hazards
identified from the risk analysis. The protocols shall identify the test purpose, set-up, equipment
(specifications, calibration, etc.), test conditions (with a justification of appropriateness to anticipated
in vivo operating conditions for the device), acceptance criteria, and sample quantities tested.
NOTE See ISO 16061.
For novel surgical heart valve substitutes (e.g. sutureless), the requirements of both this part of
ISO 5840 and ISO 5840-3 might be relevant and shall be considered, if applicable to the specific device
design and based on the results of the risk analysis.
6 © ISO 2015 – All rights reserved

ISO 5840-2:2015(E)
The manufacturer shall validate the design of the surgical heart valve substitute, its packaging/labelling,
and accessories.
7.2 In vitro assessment
7.2.1 Test conditions, sample selection, and reporting requirements
7.2.1.1 Test conditions and sample selection
Test specimens shall represent, as closely as possible, the finished product to be supplied for clinical use,
including exposure to the maximum number of recommended sterilization cycles, process chemicals,
and aging effects in accordance with all manufacturing procedures and Instructions for Use, where
appropriate. Any deviations of the test specimens from the finished product shall be justified.
The specimens selected for testing shall fully represent the total implant size range. Depending on the
particular test, testing might not necessarily have to be completed for each discrete valve size, but
shall at least be completed for the smallest, intermediate, and largest sizes. A rationale for device size
selection shall be provided.
For all tests, the number of samples shall be justified based on the specific intent of the test (see
ISO 5840-1:2015, Annex F). Sampling shall ensure adequate representation of the expected variability in
the manufacture of devices. Additional recommendations regarding sampling and sample conditioning
are included within each test method defined herein, as appropriate.
Where simulation of in vivo conditions is applicable to the test method, consideration shall be given to
those operational environments given in ISO 5840-1:2015, Table 1 and Table 2 for the adult population.
See ISO 5840-1:2015, Annex E for guidelines regarding suggested test conditions for the paediatric
population. Where applicable, testing shall be performed using a test fluid of isotonic saline, blood,
or a blood-equivalent fluid whose physical properties (e.g. specific gravity, viscosity at operating
temperatures) are appropriate to the test being performed. The test fluid used shall be justified. Testing
shall be performed at the intended operating temperature as appropriate,
Test methods for design verification testing shall be appropriately validated. Refer to applicable
sections of ISO/IEC 17025:2005.
7.2.1.2 Reporting requirements
Each test report shall include the following, at a minimum:
a) rationale for the test;
b) identification and description of the sample(s) tested (e.g. batch number);
c) identification and description of the reference valve(s);
d) number of specimens tested, and sample size rationale;
e) detailed description of the test method including measurement accuracy and repeatability of
the test system;
f) verification that appropriate quality assurance standards have been met (e.g. good laboratory
practices);
g) test results and conclusions.
Statistical procedures such as described in ISO 5840-1:2015, Annex F may be used to assist data analysis.
ISO 5840-2:2015(E)
7.2.2 Material property assessment
7.2.2.1 General
Properties of surgical heart valve substitute system shall be evaluated as applicable to the specific
design as determined by the risk assessment. The material requirements of ISO 14630 and ISO 16061
shall apply. Additional testing specific to certain materials shall be performed to determine the
appropriateness of the material for use in the design.
7.2.2.2 Biological safety
The biocompatibility of the materials and components used in surgical heart valve substitutes shall
be determined in accordance with ISO 10993-1. The test plan recorded in the risk management file
shall comprise a biological safety evaluation program with a justification for the appropriateness and
adequacy of the information obtained. The documentation shall include a rationale for the commission
of any biological safety tests carried out to supplement information obtained from other sources, and for
the omission of any tests identified by ISO 10993-1 but not performed. During the hazard identification
stage of a biological safety evaluation, sufficient information shall be obtained to allow the identification
of toxicological hazards and the potential for effects on relevant hematological characteristics. Where
an identified hazard has the potential for significant clinical effects, the toxicological risk shall be
characterized through evaluation of data on, for example, mode of action, dose-response, exposure
level, biochemical interactions, and toxicokinetics.
For surgical heart valve substitutes using animal tissue or their derivatives, the risk associated with
the use of these materials shall be evaluated in accordance with the ISO 22442- series.
7.2.2.3 Material and mechanical property testing
Material properties of all constituent materials comprising the surgical heart valve substitute shall be
evaluated as applicable to the specific design. Scientific literature citations or previous characterization
data from similar devices can be referenced; however, the applicability of the literature data to the
surgical heart valve substitute shall be justified.
Mechanical properties shall be characterized at various stages of manufacture, as applicable.
Environmental conditions that might affect device or component performance or durability shall be
evaluated and included in testing protocols (e.g. shelf life testing). ISO 5840-1:2015, Annex G provides
potentially relevant physical, mechanical, and chemical properties by material class and components.
ISO 5840-1:2015, Annex H provides a list of standards that might be applicable to the testing of materials
and components. ISO 5840-1:2015, Annex I provides guidance on mechanical property characterization
of raw and conditioned materials. ISO 5840-1:2015, Annex J provides guidance on corrosion assessment.
7.2.3 Hydrodynamic performance assessment
Hydrodynamic testing shall be performed to provide information on the fluid mechanical performance
of the surgical heart valve substitute and provide indicators of valve performance in terms of load to
the heart and potential for blood stasis and damage.
A guideline for the performing and reporting of hydrodynamic tests is given in Annex F.
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 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 conditions. The minimum
performance requirements are based on values in the published scientific literature. The values in
Table 1 and Table 2 of this part of ISO 5840 are applicable to new or modified heart valve substitutes
8 © ISO 2015 – All rights reserved

ISO 5840-2:2015(E)
which have not been clinically proven or evaluated under the previous version of ISO 5840:2005. The
haemodynamic waveforms produced by the pulse duplicator shall reasonably simulate physiological
conditions as shown in ISO 5840-1:2015, Figure 3.
Table 1 — Minimum device performance requirements, Aortic
Valve size (mm)
Parameter
17 19 21 23 25 27 29 31
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
10 10 10 10 15 15 20 20
flow volume) less than or equal to
Table 2 — Minimum device performance requirements, Mitral
Valve size (mm)
Parameter
23 25 27 29 31 33
EOA (cm ) greater than or equal to 1,05 1,25 1,45 1,65 1,90 2,15
Total Regurgitant Fraction (% of for-
15 15 15 20 20 20
ward flow volume) less than or equal to
The total regurgitant fraction shall include closing volume, transvalvular leakage volume, and
paravalvular leakage volume.
q
V
RMS
EOA=
Δp
51,6*
ρ
where
EOA is the Effective Orifice Area (cm );
is the root mean square forward flow (ml/s) during the positive differential pressure
q
V
RMS
period;
Δp is the mean pressure difference (measured during the positive differential pressure
period) (mmHg);
ρ is the density of the test fluid (g/cm ).
NOTE 1 This equation is derived from a simplified version of the Bernoulli Equation and as such has
limitations. The constant (51,6) is not dimensionless; thus this equation is only valid with the units shown.
NOTE 2 Defining the time interval for flow and pressure measurement as the positive differential pressure
period of the forward flow interval for EOA computation provides repeatable and consistent results for
comparison to the Table 1 and Table 2 reference values. It is recognized that this approach may not equate to the
EOA computation approaches employed clinically. See ISO 5840-1:2015, Figure 2.
NOTE 3 The rationale for use of q is that the instantaneous pressure difference is proportional to the
V
RMS
square of instantaneous flow rate, and it is the mean pressure difference that is required.
NOTE 4 See References [20], [17], and [21].
ISO 5840-2:2015(E)
7.2.4 Structural performance assessment
7.2.4.1 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.
7.2.4.2 Device durability assessment
An assessment of the durability of the surgical heart valve substitute shall be performed in order to
assess continued function over a
...