EN ISO 5840-1:2015

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

EN ISO 5840-1
EUROPEAN STANDARD
NORME EUROPÉENNE
September 2015
EUROPÄISCHE NORM
ICS 11.040.40
English Version
Cardiovascular implants - Cardiac valve prostheses - Part
1: General requirements (ISO 5840-1:2015)
Implants cardiovasculaires - Prothèses valvulaires - Herz- und Gefäßimplantate - Herzklappenprothesen -
Partie 1: Exigences générales (ISO 5840-1:2015) Teil 1: Allgemeine Anforderungen (ISO 5840-1:2015)
This European Standard was approved by CEN on 10 July 2015.

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

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

EUROPÄISCHES KOMITEE FÜR NORMUNG

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

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 5840-1:2015) has been prepared by Technical Committee ISO/TC 150
“Implants for surgery” in collaboration with Technical Committee CEN/TC 285 “Non-active surgical
implants” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by March 2016, and conflicting national standards shall
be withdrawn at the latest by March 2016.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).
For relationship with EU Directive(s), see informative Annex ZA, which is an integral part of this
document.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 5840-1:2015 has been approved by CEN as EN ISO 5840-1:2015 without any
modification.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices
This European Standard has been prepared under a mandate given to CEN by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has
been implemented as a national standard in at least one Member State, compliance with the clauses of
this standard given in Table ZA.1 confers, within the limits of the scope of this standard, a presumption
of conformity with the corresponding Essential Requirements of that Directive and associated EFTA
regulations.
Table ZA.1 — Correspondence between this European Standard
and Directive 93/42/EEC on medical devices
Clause(s)/sub-clause(s) Essential Requirements (ERs) Qualifying remarks/Notes
of this European Standard of Directive 93/42/EEC
5, 6, 7 7.1
5, 6.2.4, 6.4, 6.5 7.2
6.2.2, 6.2.3, 7.3 7.3
6.5 7.5
6.2.2, 6.5 7.6
5, 6.4, 6.5 8.1
6.2.4, 6.4 8.3
6.2.4 8.4
6.4 8.5
6.2.4 8.6
6.2.4 8.7
6.2.1, 6.3, 7 9.1
6.2.1, 6.3, 6.4, 6.5, 7 9.2, 1. indent
6.4, 6.5, 7 9.2, 2. indent
6.4, 6.5, 7 9.2, 3. indent
6.2.1, 6.3, 6.4, 6.5, 7 9.2, 4. indent
6.2.4 13
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this standard.
INTERNATIONAL ISO
STANDARD 5840-1
First edition
2015-09-15
Cardiovascular implants — Cardiac
valve prostheses —
Part 1:
General requirements
Implants cardiovasculaires — Prothèses valvulaires —
Partie 1: Exigences générales
Reference number
ISO 5840-1:2015(E)
©
ISO 2015
ISO 5840-1:2015(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
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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 5840-1:2015(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviations.11
5 Fundamental requirements .12
6 Device description .12
6.1 Intended use .12
6.2 Design inputs .12
6.2.1 Operational specifications .12
6.2.2 Performance specifications .12
6.2.3 Implant procedure.12
6.2.4 Packaging, labelling, and sterilization .13
6.3 Design outputs .13
6.4 Design transfer (manufacturing verification/validation) .14
6.5 Risk management .14
7 Design verification testing and analysis/design validation .15
7.1 General requirements .15
7.2 In vitro assessment .15
7.3 Preclinical in vivo evaluation .15
7.4 Clinical investigations .15
Annex A (informative) Rationale for the provisions of this part of ISO 5480 .16
Annex B (normative) Packaging .19
Annex C (normative) Product labels, instructions for use, and training .20
Annex D (normative) Sterilization .23
Annex E (informative) In vitro test guidelines for paediatric devices .24
Annex F (informative) Statistical procedures when using in vitro performance criteria .28
Annex G (informative) Examples and definitions of some physical and material properties
of heart valve systems .29
Annex H (informative) Examples of standards applicable to testing of materials and
components of heart valve systems .40
Annex I (informative) Raw and post-conditioning mechanical properties for support
structure materials .46
Annex J (informative) Corrosion assessment .48
Annex K (informative) Echocardiographic protocol .51
Bibliography .54
ISO 5840-1:2015(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
Barriers to Trade (TBT) see the following URL: Foreword - Supplementary Information
The committee responsible for this document is ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This first edition of ISO 5840-1, together with ISO 5840-2 and ISO 5840-3, cancels and replaces
ISO 5840:2005, which has been technically revised.
ISO 5840 consists of the following parts, under the general title Cardiovascular implants — Cardiac valve
prostheses:
— Part 1: General requirements
— Part 2: Surgically implanted heart valve substitutes
— Part 3: Heart valve substitutes implanted by transcatheter techniques
iv © ISO 2015 – All rights reserved

ISO 5840-1:2015(E)
Introduction
There is, as yet, no heart valve substitute which can be regarded as ideal.
The ISO 5840–series has been prepared by a group well aware of the issues associated with heart valve
substitutes and their development. In several areas, the provisions of the ISO 5840–series deliberately
have not been specified to encourage development and innovation. It does specify the types of tests,
test methods, and/or requirements for test apparatus and requires documentation of test methods
and results. The areas with which the ISO 5840–series are concerned are those which will ensure that
associated risks to the patient and other users of the device have been adequately mitigated, facilitate
quality assurance, aid the clinician in choosing a heart valve substitute, and ensure that the device will
be presented at the operating table in convenient form. Emphasis has been placed on specifying types
of in vitro testing, on preclinical in vivo and clinical evaluations, on reporting of all in vitro, preclinical in
vivo, and clinical evaluations, and on the labelling and packaging of the device. Such a process involving
in vitro, preclinical in vivo, and clinical evaluations is intended to clarify the required procedures prior
to market release and to enable prompt identification and management of any subsequent problems.
With regard to in vitro testing and reporting, apart from basic material testing for mechanical,
physical, chemical, and biocompatibility characteristics, the ISO 5840–series also covers important
hydrodynamic and durability characteristics of heart valve substitutes. The ISO 5840–series does not
specify exact test methods for hydrodynamic and durability testing, but it offers guidelines for the test
apparatus.
The ISO 5840–series is incomplete in several areas. It is intended to be revised, updated, and/or
amended as knowledge and techniques in heart valve substitute technology improve.
INTERNATIONAL STANDARD ISO 5840-1:2015(E)
Cardiovascular implants — Cardiac valve prostheses —
Part 1:
General requirements
1 Scope
This part of ISO 5840 is applicable to heart valve substitutes intended for human implantation and
provides general requirements. Subsequent parts of the ISO 5840–series provide specific requirements.
This part of ISO 5840 is applicable to both newly developed and modified heart valve substitutes and
to the accessories, packaging, and labelling required for their implantation and for determining the
appropriate size of the heart valve substitute to be implanted.
This part of ISO 5840 outlines an approach for qualifying the design and manufacture of a heart valve
substitute through risk management. The selection of appropriate qualification tests and methods
are derived from the risk assessment. The tests may include those to assess the physical, chemical,
biological, and mechanical properties of heart valve substitutes and of their materials and components.
The tests may also include those for preclinical in vivo evaluation and clinical evaluation of the finished
heart valve substitute.
This part of ISO 5840 defines operational conditions for heart valve substitutes.
This part of ISO 5840 excludes homografts.
NOTE A rationale for the provisions of this part of ISO 5840 is given in Annex A.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 5840-2, Cardiovascular implants — Cardiac valve prostheses —Part 2: Surgically implanted heart valve
substitutes
ISO 5840-3, Cardiovascular implants — Cardiac valve prostheses —Part 3: Heart valve substitutes
implanted by transcatheter techniques
ISO 11135, Sterilization of health-care products — Ethylene oxide — Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 11137 (all parts), Sterilization of health care products — Radiation
ISO 11607 (all parts), Packaging for terminally sterilized medical devices
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14160, Sterilization of health care products — Liquid chemical sterilizing agents for single-use medical
devices utilizing animal tissues and their derivatives — Requirements for characterization, development,
validation and routine control of a sterilization process for medical devices
ISO 14630:2012, Non-active surgical implants — General requirements
ISO 5840-1:2015(E)
ISO 14937, Sterilization of health care products — General requirements for characterization of a sterilizing
agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 17665 (all parts), Sterilization of health care products — Moist heat
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
accessories
device-specific tools that are required to assist in the implantation of the heart valve substitute (3.28)
3.2
adverse event
AE
untoward medical occurrence in a study subject which does not necessarily have to have a causal
relationship with study treatment
Note 1 to entry: An AE can be an unfavourable and unintended sign (including an abnormal laboratory finding),
symptom, or disease, temporary or permanent, whether or not related to the prosthetic valve implantation or
procedure.
3.3
actuarial methods
statistical technique for calculating event rates over time
Note 1 to entry: Standard actuarial methods calculate the probability of freedom from events within pre-specified
intervals of time. When the intervals approach zero width, the methods are called Kaplan-Meier methods.
3.4
arterial end diastolic pressure
minimum value of the arterial pressure during diastole
3.5
arterial peak systolic pressure
maximum value of the arterial pressure during systole (3.63)
3.6
back pressure
differential pressure applied across the valve during the closed phase
3.7
body surface area
BSA
total surface area (m ) of the human body
Note 1 to entry: This can be calculated (Mosteller’s formula) as the square root of the product of the weight in kg
times the height in cm divided by 3 600 (see Reference [31]).
3.8
cardiac index
2 2
cardiac output (3.9) (CO, L/min) divided by the body surface area (3.7) (BSA, m ) with units L/min/m
3.9
cardiac output
CO
stroke volume (3.59) times heart rate
2 © ISO 2015 – All rights reserved

ISO 5840-1:2015(E)
3.10
closing volume
portion of the regurgitant volume (3.48) that is associated with the dynamics of valve closure during a
single cycle (3.15)
Note 1 to entry: See Figure 1.
3.11
coating
thin-film material that is applied to an element of a heart valve system (3.29) to modify its physical or
chemical properties
3.12
compliance
relationship between change in diameter and change in pressure of a deformable tubular structure (e.g.
valve annulus, aorta, conduit) defined in this part of ISO 5840 as
()rr−×100
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;
p is the systolic pressure, in mmHg;
r is the inner radius at p , in millimetres;
1 1
r is the inner radius at p , in millimetres.
2 2
Note 1 to entry: Reference ISO 25539-1.
ISO 5840-1:2015(E)
Key
X time
Y flowrate
1 closing volume
2 leakage volume
Figure 1 — Schematic representation of flow waveform and regurgitant volumes for one cycle
3.13
component-joining material
material such as a suture, adhesive, or welding compound used to assemble the components of a heart
valve system (3.29)
3.14
cumulative incidence
statistical technique where events other than death can be described by the occurrence of the event
over time without including death of the subjects
Note 1 to entry: Cumulative incidence is also known as “actual” analysis.
3.15
cycle
one complete sequence in the action of a heart valve substitute (3.28) under pulsatile-flow conditions
3.16
cycle rate
number of complete cycles (3.15) per unit of time usually expressed as cycles per minute (cycles/min)
3.17
design verification
establishment by objective evidence that the design output meets the design input requirements
3.18
design validation
establishment by objective evidence that device specifications conform with user needs and intended
use(s) (3.31)
4 © ISO 2015 – All rights reserved

ISO 5840-1:2015(E)
3.19
device embolization
dislodgement from the intended and documented original position to an unintended and non-
therapeutic location
3.20
device failure
inability of a device to perform its intended function sufficient to cause a hazard
3.21
device migration
detectable movement or displacement of the heart valve substitute (3.28) from its original position
within the implant position (3.30) and without device embolization (3.19)
3.22
effective orifice area
EOA
orifice area that has been derived from flow and pressure or velocity data
q
V
RMS
For in vitro testing, EOA is defined as:EOA=
Δp
51,6×
ρ
where
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 to entry: See 3.53.
3.23
failure mode
mechanism of device failure (3.20)
Note 1 to entry: Support structure fracture, calcification, and prolapse are examples of failure modes.
3.24
flexible surgical heart valve substitute
surgical heart valve substitute (3.62) wherein the occluder (3.40) is flexible under physiological
conditions
Note 1 to entry: The orifice ring may or may not be flexible.
3.25
follow-up
continued assessment of patients who have received the heart valve substitute (3.28)
3.26
forward flow volume
volume of flow ejected through the heart valve substitute (3.28) in the forward direction during one
cycle (3.15)
ISO 5840-1:2015(E)
3.27
fracture
complete separation of any structural component of the heart valve substitute (3.28) that was previously
intact
3.28
heart valve substitute
device used to replace the function of a natural valve of the heart
3.29
heart valve system
implantable device, accessories (3.1), packaging, labelling, and instructions
3.30
implant site/implant position
intended location of heart valve substitute (3.28) implantation or deployment
3.31
intended use
use of a product or process in accordance with the specifications, instructions, and information
provided by the manufacturer
3.32
Kaplan-Meier methods
statistical approaches for calculating event rates over time when the actual dates of events for each
person in the population are known
3.33
leakage volume
portion of the regurgitant volume (3.48) which is associated with leakage during the closed phase of a
valve in a single cycle (3.15) and is the sum of the transvalvular leakage volume (3.66) and paravalvular
leakage volume (3.43)
Note 1 to entry: The point of separation between the closing and leakage volumes is obtained according to a
defined and stated criterion (the linear extrapolation shown in Figure 1 is just an example).
3.34
linearized rate
total number of events divided by the total time under evaluation
Note 1 to entry: Generally, the rate is expressed in terms of percent per patient year.
3.35
major bleeding
any episode of major internal or external bleeding that causes death, hospitalization, or permanent
injury (e.g. vision loss) or necessitates transfusion
3.36
major paravalvular leak
paravalvular leakage leading to death or reintervention, 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
3.37
mean arterial pressure
time-averaged arithmetic mean value of the arterial pressure during one cycle (3.15)
3.38
mean pressure difference/mean pressure gradient
time-averaged arithmetic mean value of the pressure difference across a heart valve substitute (3.28)
during the positive differential pressure period of the cycle (3.15)
6 © ISO 2015 – All rights reserved

ISO 5840-1:2015(E)
3.39
nonstructural valve dysfunction
abnormality extrinsic to the heart valve substitute (3.28) that results in stenosis, regurgitation, and/or
haemolytic anemia
3.40
occluder/leaflet
component that inhibits backflow
3.41
outflow tract profile height
maximum distance that the heart valve substitute (3.28) extends axially into the outflow tract in the
open or closed position, whichever is greater, measured from the valve structure intended to mate with
the top (atrial or aortic/pulmonic side) of the patient’s annulus
3.42
pannus
ingrowth of tissue onto the heart valve substitute (3.28) which can interfere with normal functioning
3.43
paravalvular leakage volume
portion of the leakage volume (3.33) that is associated with leakage around the closed heart valve
substitute during a single cycle (3.15)
3.44
profile height
maximal axial dimension of a heart valve substitute (3.28) in the open or closed position, whichever is
greater
3.45
prosthetic valve endocarditis
any infection involving a prosthetic valve based on reoperation, autopsy, or the Duke Criteria for
endocarditis
3.46
reference valve
heart valve substitute (3.28) with a known clinical experience used for comparative preclinical and
clinical evaluations
3.47
regurgitant fraction
regurgitant volume (3.48) expressed as a percentage of the forward flow volume (3.26)
3.48
regurgitant volume
volume of fluid that flows through a heart valve substitute (3.28) in the reverse direction during one
cycle (3.15) and is the sum of the closing volume (3.10) and the leakage volume (3.33)
Note 1 to entry: See Figure 1.
3.49
rigid surgical heart valve substitute
surgical heart valve substitute (3.62) wherein the occluder(s) (3.40) and orifice ring are non-flexible
under physiological conditions
3.50
risk
combination of the probability of occurrence of harm and the severity (3.55) of that harm
[SOURCE: ISO 14971, 2.16]
ISO 5840-1:2015(E)
3.51
risk analysis
systematic use of available information to identify hazards and to estimate the associated risks (3.50)
[SOURCE: ISO 14971, 2.17]
3.52
risk assessment
overall process comprising a risk analysis (3.51) and a risk evaluation
[SOURCE: ISO 14971, 2.18]
3.53
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
qt() dt
∫ V
t
q =
V
RMS
tt−
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;
t is time at end of positive differential pressure period.
Note 3 to entry: The rationale for use of q is that the instantaneous pressure difference is proportional to
V
RMS
the square of instantaneous flow rate and it is the mean pressure difference (3.38) that is required.
Note 4 to entry: See Figure 2.
8 © ISO 2015 – All rights reserved

ISO 5840-1:2015(E)
Key
1 aortic pressure
2 left ventricle pressure
3 aortic flow rate
X time (sec)
Y pressure (mmHg) and flow (L/min)
a
Positive pressure range.
b
q range.
V
RMS
Figure 2 — Schematic representation of the positive pressure period of an aortic forward flow
interval
3.54
safety
freedom from unacceptable risk
[SOURCE: ISO 14971, 2.24]
3.55
severity
measure of the possible consequences of a hazard
[SOURCE: ISO 14971, 2.25]
ISO 5840-1:2015(E)
3.56
simulated cardiac output
forward flow volume (3.26) times heart rate
3.57
sterility assurance level
SAL
probability of a single viable microorganism occurring on an item after sterilization (3.58)
−6 −3
Note 1 to entry: The term SAL takes a quantitative value, generally 10 or 10 . When applying this quantitative
−6
value to assurance of sterility, an SAL of 10 has a lower value, but provides a greater assurance of sterility than
−3
an SAL of 10 .
[SOURCE: ISO/TS 11139, 2.46]
3.58
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 3.57.
[SOURCE: ISO/TS 11139:2006]
3.59
stroke volume
SV
volume of blood pumped by a ventricle in one contraction
3.60
structural valve deterioration
change in the function of a heart valve substitute (3.28) resulting from an intrinsic abnormality that
causes stenosis or regurgitation
Note 1 to entry: This definition excludes infection or thrombosis of the heart valve substitute. It includes intrinsic
changes such as wear, fatigue failure, stress fracture, occluder escape, suture line disruption of components of
the prosthesis, calcification, cavitation erosion, leaflet tear, and stent creep.
3.61
support structure
component of a heart valve substitute (3.28) that houses the occluder(s) (3.40) (e.g. stent, frame, housing)
3.62
surgical heart valve substitute
heart valve substitute (3.28) generally requiring direct visualization and cardiopulmonary bypass for
implantation
3.63
systolic duration
systole
portion of cardiac cycle time corresponding to ventricular contraction
Note 1 to entry: See Figure 3.
3.64
thromboembolism
embolic event involving clot that occurs in the absence of infection
Note 1 to entry: Thromboembolism may be manifested by a neurological event or a noncerebral embolic event.
10 © ISO 2015 – All rights reserved

ISO 5840-1:2015(E)
3.65
transcatheter heart valve substitute
heart valve substitute (3.28) delivered through a catheter and implanted in a manner generally not
involving direct visualization and generally involving a beating heart
3.66
transvalvular leakage volume
component of the leakage volume (3.33) that is associated with leakage through the closed valve during
a single cycle (3.15)
Figure 3 — Wiggers Diagram, showing various events of a cardiac cycle
3.67
usability
characteristic of the user interface that establishes effectiveness, efficiency, ease of user learning and
user satisfaction
4 Abbreviations
For the purposes of this document, the following abbreviations apply.
AE Adverse Event
AF Atrial Fibrillation
AWT Accelerated Wear Testing
BSA Body Surface Area
ECG Electrocardiogram
EOA Effective Orifice Area
FEA Finite Element Analysis
ISO 5840-1:2015(E)
IEC International Electrotechnical Commission
IFU Instructions For Use
IOD Internal Orifice Diameter
LV Left Ventricle, Left Ventricular
MAP Mean Arterial Pressure
MRI Magnetic Resonance Imaging
RV Right Ventricle, Right Ventricular
5 Fundamental requirements
The manufacturer shall determine, at all stages of the product life cycle, the acceptability of the product
for clinical use.
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, intended device delivery approach/process, 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. Table 1 and Table 2 define the expected physiological
parameters of the intended adult patient population for heart valve substitutes for both normal and
pathological patient conditions.
Refer to Annex E for in vitro test guidelines for paediatric devices.
6.2.2 Performance specifications
The manufacturer shall establish (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 specific performance specifications are provided in ISO 5840-2 and
ISO 5840-3.
6.2.3 Implant procedure
The entire system shall provide intended users the ability to safely and effectively perform all required
pre-operative, intra-operative, and post-operative procedural tasks and achieve all desired objectives.
This shall include all other device specific tools and accessories that intended users will use to complete
the procedure.
NOTE For guidance on how to determine and establish design attributes pertaining to the use of the system
to conduct the implant procedure, see IEC 62366.
12 © ISO 2015 – All rights reserved

ISO 5840-1:2015(E)
Table 1 — Heart valve substitute operational environment for left side of heart — Adult
population
Parameter General condition
Surrounding medium Human heart/Human blood
Temperature 34 °C to 42 °C
Heart rate 30 bpm to 200 bpm
Cardiac output 3 L/min to 15 L/min
Forward flow volume 25 mL to 100 mL
Peak differential pressure across
Arterial peak Arterial end
Blood pressures and
a
closed valve
systolic diastolic
resultant pressure
pressure pressure
Aortic ΔP Mitral ΔP
loads by patient
A M
condition
mmHg mmHg
mmHg mmHg
Normotensive 120 80 100 120
Hypotensive 60 40 50 60
Hypertensive
Mild 140 to 159 90 to 99 115 to 129 140 to 159
Moderate 160 to 179 100 to 109 130 to 144 160 to 179
Severe 180 to 209 110 to 119 145 to 164 180 to 209
Very Severe ≥210 ≥120 ≥165 ≥210
a
Peak differential pressure across closed aortic valve estimated clinically using the following relationship:
—  ΔP ≈ pressure associated with dicrotic notch assuming LV pressure is zero ≈ Arterial End Diastolic Pressure +
A
1/2(Arterial Peak Systolic Pressure – Arterial End Diastolic Pressure).
—  Peak differential pressure across closed mitral valve estimated to be equivalent to Arterial Peak Systolic Pressure.
6.2.4 Packaging, labelling, and sterilization
The heart valve system shall meet the requirements for packaging, labelling, and sterilization contained
within Annex B, Annex C, and Annex D, respectively.
The manufacturer shall provide sufficient information and guidance in the labelling to allow for
appropriate preparation of the implant site, accurate selection of appropriate implant size, and reliable
implantation of the heart valve substitute.
6.3 Design outputs
The manufacturer shall establish (i.e. define, document, and implement) a complete specification of
the heart valve system including component and assembly-level specifications, delivery system (if
applicable), accessories, packaging, and labelling. In addition to the physical components of the heart
valve system, the implant procedure itself should be considered an important element of safe and
effective heart valve therapy.
ISO 5840-1:2015(E)
Table 2 — Heart valve substitute operational environment for right side of heart — Adult
population
Parameter General Condition
Surrounding medium Human heart/Human blood
Temperature 34 °C to 42 °C
Heart rate 30 bpm to 200 bpm
Cardiac output 3 L/min to 15 L/min
Forward flow volume 25 mL to 100 mL
Peak differential pressure across closed
Pulmonary
Right ventricle
a
Blood pressures and valve
artery end
peak systolic
resultant pressure
diastolic
Pulmonary Tricuspid
pressure
loads by patient
pressure
ΔP ΔP
P T
condition
mmHg
mmHg
mmHg mmHg
Normotensive 18 to 35 8 to 15 13 to 25 18 to 35
Hypotensive 15 5 10 15
Hypertensive
Mild 40 to 49 15 to 19 28 to 34 40 to 49
Moderate 50 to 59 20 to 24 35 to 42 50 to 59
Severe 60 to 84 25 to 34 43 to 59 60 to 84
Very Severe ≥85 ≥35 ≥60 ≥85
a
Peak differential pressure across closed pulmonic valve estimated clinically using the following relationship:
—  ΔP approximately pressure associated with dicrotic notch assuming RV pressure is zero approximately Pulmonary
P
Artery End Diastolic Pressure + 1/2(Right Ventricle Peak Systolic Pressure –Pulmonary Artery End Diastolic Pressure).
—  Peak differential pressure across closed tricuspid valve estimated to be equivalent to Right Ventricle Peak Systolic
Pressure.
6.4 Design transfer (manufacturing verification/validation)
The manufacturer shall generate a flowchart identifying the manufacturing process operations and
inspection steps. The flowchart shall indicate the input of all components and important manufacturing
materials.
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.
The manufacturer shall establish the adequacy of full scale manufacturing by validation of the
manufacturing process. The manufacturer shall validate all special processes and process software
and document the results of the validation.
NOTE See ISO 13485.
6.5 Risk management
The manufacturer shall define and implement a risk management program in accordance with
ISO 14971.
14 © ISO 2015 – All ri
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