EN ISO 5840-3:2013

SLOVENSKI STANDARD
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Cardiovascular implants - Cardiac valve prostheses - Part 3: Heart valve substitutes
implanted by transcatheter techniques (ISO 5840-3:2013)
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 3: Durch minimal-invasive
Methoden implantierter Herzklappenersatz (ISO 5840-3:2013)
Implants cardiovasculaires - Prothèses valvulaires - Partie 3: Valves cardiaques de
substitution implantées par des techniques transcathéter (ISO 5840-3:2013)
Ta slovenski standard je istoveten z: EN ISO 5840-3:2013
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.

EUROPEAN STANDARD
EN ISO 5840-3
NORME EUROPÉENNE
EUROPÄISCHE NORM
March 2013
ICS 11.040.40
English Version
Cardiovascular implants - Cardiac valve prostheses - Part 3:
Heart valve substitutes implanted by transcatheter techniques
(ISO 5840-3:2013)
Implants cardiovasculaires - Prothèses valvulaires - Partie Herz- und Gefäßimplantate - Herzklappenprothesen - Teil
3: Valves cardiaques de substitution implantées par des 3: Durch minimal-invasive Methoden implantierter
techniques transcathéter (ISO 5840-3:2013) Herzklappenersatz (ISO 5840-3:2013)
This European Standard was approved by CEN on 21 January 2013.

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

Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2013 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 5840-3:2013: E
worldwide for CEN national Members.

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

Foreword
This document (EN ISO 5840-3:2013) 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 September 2013, and conflicting national standards shall be
withdrawn at the latest by September 2013.
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 5840-3:2013 has been approved by CEN as EN ISO 5840-3:2013 without any modification.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC
This European Standard has been prepared under a mandate given to CEN by the European Commission
and the European Free Trade Association to provide one means of conforming to Essential Requirements of
the New Approach Directive 93/42/EEC, 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

Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes
European Standard of Directive 93/42/EEC

Annex C 7.2
7.2.2, 7.2.3 and 7.2.10 7.3
7.2.2.2 8.2
6.2.2.3 d), 6.4 and Annex C 8.3

6.2.4 and Annex E 8.4
6.4 8.5
6.2.2.3 c) and 7.2.5.2 9.2, 3rd indent

6.2.2.1 e) and 7.2.4 9.2, 4th indent
D.1.3 13.1 For labelling requirements consider
also ISO 14630:—, 11.2.
D.1.2 b) 13.3 a)
D.1.1 d), D.1.2 e) and f ) 13.3 b)

D.1.1 e) and D.1.2 g) 13.3 c)
D.1.1 c) and D.1.2 d) 13.3 d)
D.1.1 f ) and D.1.2 h) 13.3 e)

D.1.1 g) and D.1.2 i) 13.3 f )

D.1.2 j) 13.3 h)
D.1.2 k) 13.3 i)
D.1.2 l) 13.3 k)
D.1.1 e) and D.1.2 g) 13.3 m)
D.1.3 a), b), d), i), k), l) and m) 13.6 a)
Table
(continued)
Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes
European Standard of Directive 93/42/EEC

D.1.3 e) and u) 13.6 b)
D.1.3 g) 13.6 c)
D.1.3 p) 13.6 f )
D.1.3 n) 13.6 g)
D.1.3 r) 13.6 i)
D.1.3 p) 13.6 n)
D.1.3 c) 13.6 q)
WARNING — Other requirements and other EU Directives may be applicable to the product(s)
falling within the scope of this standard.

INTERNATIONAL ISO
STANDARD 5840-3
First edition
2013-03-01
Cardiovascular implants — Cardiac
valve prostheses —
Part 3:
Heart valve substitutes implanted by
transcatheter techniques
Implants cardiovasculaires — Prothèses valvulaires —
Partie 3: Valves cardiaques de substitution implantées par des
techniques transcathéter
Reference number
ISO 5840-3:2013(E)
©
ISO 2013
ISO 5840-3:2013(E)
© ISO 2013
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
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Tel. + 41 22 749 01 11
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Published in Switzerland
ii © ISO 2013 – All rights reserved

ISO 5840-3:2013(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviations.10
5 Fundamental requirements .10
6 Device description .10
6.1 Intended use .10
6.2 Design inputs .10
6.3 Design outputs .13
6.4 Design transfer (manufacturing verification/validation) .13
6.5 Risk management .14
7 Design verification testing and analysis/design validation .14
7.1 General requirements .14
7.2 In vitro assessment .14
7.3 Preclinical in vivo evaluation .23
7.4 Clinical investigations .26
Annex A (informative) Rationale for the provisions of this part of ISO 5840 .31
Annex B (informative) Examples of transcatheter heart valve substitutes, components and
delivery systems .34
Annex C (normative) Packaging .40
Annex D (normative) Product labels, instructions for use and training .41
Annex E (normative) Sterilization .44
Annex F (informative) Valve description .45
Annex G (informative) Transcatheter heart valve substitute hazards, associated failure modes and
evaluation methods .47
Annex H (informative) In vitro test guidelines for paediatric devices .51
Annex I (informative) Statistical procedures when using performance criteria .55
Annex J (informative) Examples and definitions of some physical and material properties of
transcatheter heart valve substitutes and their components .56
Annex K (informative) Examples of standards applicable to testing of materials and components
of transcatheter heart valve substitutes .69
Annex L (informative) Raw and post-conditioning mechanical properties for support
structure materials .75
Annex M (informative) Corrosion assessment .77
Annex N (informative) Guidelines for verification of hydrodynamic performance.80
Annex O (informative) Durability testing .84
Annex P (informative) Fatigue assessment .86
Annex Q (informative) Preclinical in vivo evaluation .92
Annex R (normative) Adverse event classification during clinical investigation .95
Annex S (informative) Echocardiographic protocol .100
ISO 5840-3:2013(E)
Bibliography .103
iv © ISO 2013 – All rights reserved

ISO 5840-3:2013(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.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International
Standards adopted by the technical committees are circulated to the member bodies for voting.
Publication as an International Standard requires approval by at least 75 % of the member bodies
casting a vote.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights.
ISO 5840-3 was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
ISO 5840 consists of the following parts, under the general title Cardiovascular implants — Cardiac
valve prostheses:
— Part 3: Heart valve substitutes implanted by minimally invasive techniques
ISO 5840-3:2013(E)
Introduction
No heart valve substitute is ideal. Therefore, a group of engineers, scientists and clinicians well aware
of the problems associated with heart valve substitutes and their development has prepared this part
of ISO 5840. In several areas, the provisions of this part of ISO 5840 have been deliberately left partially
defined so as not to inhibit development and innovation. This part of ISO 5840 specifies types of tests,
test methods and requirements for test apparatus. It requires documentation of test methods and
results. This part of ISO 5840 deals with those areas that will ensure adequate mitigation of device-
associated risks for patients and other users of the device, facilitate quality assurance, aid the cardiac
surgeon and cardiologist in choosing a heart valve substitute, and ensure that the device will be
presented in a convenient form. This part of ISO 5840 emphasizes the need to specify types of in vitro
testing, preclinical in vivo and clinical evaluations as well as to report all in vitro, preclinical in vivo and
clinical evaluations. It describes the labels and packaging of the device. Such a process involving in vitro,
preclinical in vivo and clinical evaluations is intended to clarify the required procedures prior to market
release and to enable prompt identification and management of any subsequent problems.
With regard to in vitro testing and reporting, apart from basic material testing for mechanical, physical,
chemical and biocompatibility characteristics, this part of ISO 5840 also covers important hydrodynamic
and durability characteristics of transcatheter heart valve substitutes and their delivery systems. This
part of ISO 5840 does not specify exact test methods for hydrodynamic and durability testing but it
offers guidelines for the test apparatus.
This part of ISO 5840 should be revised, updated and amended as knowledge and techniques in heart
valve substitute technology improve.
This part of ISO 5840 is to be used in conjunction with ISO 5840:2005, which will be replaced by
ISO 5840-1 in future.
vi © ISO 2013 – All rights reserved

INTERNATIONAL STANDARD ISO 5840-3:2013(E)
Cardiovascular implants — Cardiac valve prostheses —
Part 3:
Heart valve substitutes implanted by transcatheter
techniques
1 Scope
This part of ISO 5840 outlines an approach for verifying/validating the design and manufacture
of a transcatheter heart valve substitute through risk management. The selection of appropriate
verification/validation tests and methods are to be derived from the risk assessment. The tests may
include those to assess the physical, chemical, biological and mechanical properties of heart valve
substitutes and of their materials and components. The tests can also include those for preclinical in
vivo evaluation and clinical evaluation of the finished heart valve substitute.
This part of ISO 5840 defines operational conditions and performance requirements for transcatheter
heart valve substitutes where adequate scientific and/or clinical evidence exists for their justification.
This part of ISO 5840 is applicable to all devices intended for implantation in human hearts as a
transcatheter heart valve substitute.
This part of ISO 5840 is applicable to both newly developed and modified transcatheter heart valve
substitutes and to the accessory devices, packaging and labelling required for their implantation and for
determining the appropriate size of heart valve substitute to be implanted.
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 valve-in-valve configurations and homografts.
This part of ISO 5840 does not specifically address non-traditional surgically implanted heart valve
substitutes (e.g. sutureless). For these devices, the requirements of both this part of ISO 5840 and
ISO 5840:2005 might be relevant and can be considered.
NOTE A rationale for the provisions of this part of ISO 5840 is given in Annex A.
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated
references, only the edition cited applies. For undated references, the latest edition of the referenced
document (including any amendments) applies.
ISO 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 11135-1, Sterilization of health care products — Ethylene oxide — Part 1: Requirements for development,
validation and routine control of a sterilization process for medical devices
ISO/TS 11135-2, Sterilization of health care products — Ethylene oxide — Part 2: Guidance on the application
of ISO 11135-1
ISO 5840-3:2013(E)
ISO 11137-1, Sterilization of health care products — Radiation — Part 1: Requirements for development,
validation and routine control of a sterilization process for medical devices
ISO 11137-2, Sterilization of health care products — Radiation — Part 2: Establishing the sterilization dose
ISO 11137-3, Sterilization of health care products — Radiation — Part 3: Guidance on dosimetric aspects
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,
sterile barrier systems and packaging systems
ISO 11607-2, Packaging for terminally sterilized medical devices — Part 2: Validation requirements for
forming, sealing and assembly processes
ISO 14155, 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 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 17665-1, Sterilization of health care products — Moist heat — Part 1: Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 22442-1, Medical devices utilizing animal tissues and their derivatives — Part 1: Application of risk
management
ISO 22442-2, Medical devices utilizing animal tissues and their derivatives — Part 2: Controls on sourcing,
collection and handling
ISO 22442-3, Medical devices utilizing animal tissues and their derivatives — Part 3: Validation of the
elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents
ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories
IEC 62366, Medical devices — Application of usability engineering to medical devices
ASTM F2052, Standard test method for measurement of magnetically induced displacement force 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
ASTM F2213, Standard test method for measurement of magnetically induced torque on medical devices in
the magnetic resonance environment
ASTM F2182, Standard test method for measurement of radio frequency induced heating near passive
implants during magnetic resonance imaging
ASTM F2119, Standard test method for evaluation of MR image artifacts from passive implants
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
NOTE Additional definitions can be found in the informative annexes.
2 © ISO 2013 – All rights reserved

ISO 5840-3:2013(E)
3.1
accessories
device-specific tools that are required to assist in the implantation of the transcatheter heart valve substitute
3.2
adverse event
AE
untoward medical occurrence in a study subject which does not necessarily have to have a causal
relationship with study treatment
Note 1 to entry: An AE can be an 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
arterial end diastolic pressure
minimum value of the arterial pressure during diastole
3.4
arterial peak systolic pressure
maximum value of the arterial pressure during systole
3.5
back pressure
differential pressure applied across the valve during the closed phase
3.6
body surface area
A
bs
total surface area (m ) of the human body
Note 1 to entry: This can be calculated (Mosteller’s formula) as the square root of product of the weight in kg
[12]
times the height in cm divided by 3 600 (see Reference ).
3.7
cardiac index
2 2
cardiac output (CO, l/min) divided by the body surface area (A , m ), in units l/min/m
bs
3.8
closing volume
portion of the regurgitant volume that is associated with the dynamics of the valve closure during
a single cycle
Note 1 to entry: See Figure 1.
ISO 5840-3:2013(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
3.9
coating
thin-film material that is applied to an element of a heart valve substitute to modify its physical or
chemical properties
3.10
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: See ISO 25539-1.
4 © ISO 2013 – All rights reserved

ISO 5840-3:2013(E)
3.11
component-joining material
material, such as a suture, adhesive or welding compound, used to assemble the components of a heart
valve substitute, thereby becoming part of the implant device
Note 1 to entry: See examples in Annex B.
3.12
cycle
one complete sequence in the action of a heart valve substitute under pulsatile flow conditions
3.13
cycle rate
number of complete cycles per unit of time, usually expressed as cycles per minute (cycles/min)
3.14
delivery approach
anatomical access used to deliver the implant to the implant site (e.g. transfemoral, transapical, transeptal)
3.15
delivery system
catheter or other device-based system used to deliver the implant to the implant site
3.16
deployed valve diameter
outer diameter (mm) of the implantable device when deployed within the target implant site in an
idealized circular configuration
3.17
device embolization
dislodgement from the intended and documented original position to an unintended and non-
therapeutic location
3.18
device failure
inability of a device to perform its intended function sufficient to cause a hazard
3.19
device migration
detectable movement or displacement of the device from its original position within the implant site,
without embolization
3.20
effective orifice area
EOA
orifice area that has been derived from flow and pressure or velocity data
3.21
failure mode
mechanism of device failure
Note 1 to entry: Catastrophic support structure fracture, calcification and prolapse are examples of failure modes.
3.22
follow-up
continued assessment of patients who have received the heart valve substitute
3.23
forward flow volume
volume of flow ejected through the test heart valve substitute in the forward direction during one cycle
ISO 5840-3:2013(E)
3.24
fracture
disruption, under the action of applied stress or strain, of any part of the transcatheter heart valve
substitute that was previously intact
3.25
heart valve substitute
device used to replace the function of a natural valve of the heart
Note 1 to entry: See examples in Annex B.
3.26
imaging modality
imaging method used to facilitate delivery and/or retrieval of the implant within the target implant site,
as well as to assess valve performance after implantation
3.27
implant site
intended site of transcatheter heart valve substitute deployment
3.28
intended use
use of a product, process or service in accordance with the specifications, instructions and information
provided by the manufacturer
3.29
leakage volume
component of the regurgitant volume that is associated with leakage during closed phase of a valve in a
single cycle and is the sum of the transvalvular leakage volume and paravalvular leakage volume
Note 1 to entry: The point of separation between the closing and leakage volumes is obtained according to a
defined and stated criterion (the linear extrapolation shown in Figure 1 is just an example).
Note 2 to entry: See Figure 1.
3.30
mean arterial pressure
time-averaged arithmetic mean value of the arterial pressure during one cycle
3.31
mean pressure difference
time-averaged arithmetic mean value of the pressure difference across a heart valve substitute during
the forward flow phase of the cycle
3.32
non-structural valve dysfunction
abnormality extrinsic to the transcatheter heart valve substitute that results in valve dysfunction
(stenosis, regurgitation or both)
3.33
occluder/leaflet
component that inhibits back flow
Note 1 to entry: See examples in Annex B.
3.34
paravalvular leakage volume
component of the leakage volume that is associated with leakage around the closed heart valve substitute
during a single cycle
6 © ISO 2013 – All rights reserved

ISO 5840-3:2013(E)
3.35
reference valve
heart valve substitute with a known clinical experience used for comparative preclinical and clinical
evaluations
3.36
regurgitant fraction
regurgitant volume expressed as a percentage of the forward flow volume
3.37
regurgitant volume
volume of fluid that flows through a heart valve substitute in the reverse direction during one cycle and
is the sum of the closing volume and the leakage volume
Note 1 to entry: See Figure 1.
3.38
repositioning
change in implant position of a partially or fully deployed transcatheter heart valve substitute via a
transcatheter technique, possibly requiring full or partial recapturing of the device
3.39
retrieval
removal of a partially or fully deployed transcatheter heart valve substitute via a transcatheter technique
3.40
risk
combination of the probability of occurrence of harm and the severity of that harm
Note 1 to entry: Adapted from ISO 14971.
3.41
risk analysis
systematic use of available information to identify hazards and to estimate the associated risks
Note 1 to entry: Adapted from ISO 14971.
3.42
risk assessment
overall process comprising a risk analysis and a risk evaluation
Note 1 to entry: Adapted from ISO 14971.
3.43
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: See Figure 2.
ISO 5840-3:2013(E)
Key title
1 aortic pressure
2 left ventricular pressure
3 aortic flow rate
a
Positive pressure range.
b
Q range.
rms
Figure 2 — Schematic representation of the positive pressure period of an aortic forward
flow interval
3.44
safety
freedom from unacceptable risk
Note 1 to entry: Adapted from ISO 14971.
3.45
severity
measure of the possible consequences of a hazard
Note 1 to entry: Adapted from ISO 14971.
3.46
special processes
processes for which the product cannot be fully verified by inspection or test
8 © ISO 2013 – All rights reserved

ISO 5840-3:2013(E)
3.47
sterility assurance level
SAL
probability of a single viable microorganism occurring on an item after sterilization
-6 -3
Note 1 to entry: The term SAL takes a quantitative value, generally 10 or 10 . When applying this quantitative
-6
value to assurance of sterility, an SAL of 10 has a lower value but provides a greater assurance of sterility than
-3
an SAL of 10 .
[ISO/TS 11139, definition 2.46]
3.48
sterilization
validated process used to render product free from viable microorganisms
Note 1 to entry: In a sterilization process, the nature 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 sterility assurance level (3. 47).
Note 3 to entry: Adapted from ISO/TS 11139.
3.49
structural component failure
degradation of structural integrity of the support structure (e.g. strut fractures) that results in the
functional performance of the implant no longer being acceptable and/or that results in adverse events
3.50
structural valve dysfunction
structural abnormality intrinsic to the transcatheter heart valve substitute that results in valve
dysfunction (stenosis and/or transvalvular and/or paravalvular regurgitation)
3.51
support structure
portion of the transcatheter heart valve substitute that transfers loads between occluder and implant
site and anchors the device within the implant site
3.52
surgically implanted heart valve substitute
heart valve substitute generally requiring direct visualization and cardiopulmonary bypass for implantation
3.53
transcatheter heart valve substitute
heart valve substitute implanted in a manner generally not involving direct visualization, and generally
involving a beating heart
3.54
transcatheter heart valve system
implantable device, delivery system, accessories, packaging, labelling and instructions
3.55
transvalvular leakage volume
component of the leakage volume that is associated with leakage through the closed valve during a
single cycle
3.56
usability
characteristic of the user interface that establishes effectiveness, efficiency, ease of user learning and
user satisfaction
ISO 5840-3:2013(E)
3.57
valve loading
process to affix or attach a transcatheter heart valve substitute onto a delivery device and collapse the
valve (e.g. reduce its diameter) for insertion via the delivery system (e.g. catheter), performed either
during manufacture or in the clinic
4 Abbreviations
For the purposes of this part of ISO 5840, the following abbreviations apply.
AE Adverse event
EOA Effective orifice area
AWT Accelerated wear testing
CFD Computational fluid dynamics
ECG Electrocardiogram
FEA Finite element analysis
IFU Instructions for use
LV Left ventricle, left ventricular
MAP Mean arterial pressure
MRI Magnetic resonance imaging
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 transcatheter heart valve substitutes for both
normal and pathological patient conditions.
10 © ISO 2013 – All rights reserved

ISO 5840-3:2013(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
Peak differential pressure
Arterial peak Arterial end
a
across closed valve
Blood pressures and resultant pressure loads systolic diastolic
by patient condition pressure pressure
Aortic Δp Mitral Δp
A M
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 is estimated using the following relationship:
— ΔP approximately pressure associated with dicrotic notch assuming LV pressure is zero approximately arterial end
Aortic
diastolic pressure + 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.
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
Pulmonary
Right ventricle
a
across closed valve
artery end
Blood pressures and resultant pressure loads peak systolic
diastolic
Pulmonary Tricuspid
by patient condition pressure
pressure
Δp Δp
P T
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
a
Peak differential pressure across closed pulmonary valve is estimated using the following relationship:
— ΔP approximate pressure associated with dicrotic notch assuming RV pressure is zero approximately pulmonary
pulmonic
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.
ISO 5840-3:2013(E)
Table 2 (continued)
Parameter General condition
Severe 60 to 84 25 to 34 43 to 59 60 to 84
Very severe 85 to 120 ≥ 35 60 to 78 85 to 120
a
Peak differential pressure across closed pulmonary valve is estimated using the following relationship:
— ΔP approximate pressure associated with dicrotic notch assuming RV pressure is zero approximately pulmonary
pulmonic
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.
6.2.2 Performance specifications
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
describe a safe and effective transcatheter heart valve substitute system.
6.2.2.1 Implantable device
The design attribute requirements of ISO 14630:2012, Clause 5, shall apply. The intended performance
of the transcatheter heart valve substitute shall take into account at least the following:
a) the ability to be consistently, accurately and safely loaded onto the delivery system;
b) the ability to be consistently, accurately and safely deployed;
c) the ability to be safely retrieved and/or repositioned (if applicable);
d) the ability to ensure effective fixation within the target implant site;
e) the ability to maintain structural and functional integrity during the expected lifetime of the device;
f) the ability to conform with anatomical structures within the implant site (e.g. in the aortic position,
there is potential for interaction with coronary ostia, anterior mitral leaflet, AV bundle branch);
g) the ability to allow forward flow with acceptably small mean pressure difference;
h) the ability to prevent retrograde flow with acceptably small regurgitation, including paravalvular
leakage;
i) the ability to resist migration and embolization during the expected lifetime of the device;
j) the ability to minimize haemolysis;
k) the ability to minimize thrombus formation;
l) the ability to maintain its functionality for the intended application consistent with the target
patient population.
6.2.2.2 Delivery system
The design attributes to meet the intended performance of the delivery system shall take into account
at least the following:
a) the ability to permit co
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