ISO 5910:2018
(Main)Cardiovascular implants and extracorporeal systems — Cardiac valve repair devices
Cardiovascular implants and extracorporeal systems — Cardiac valve repair devices
1.1 This document applies to all heart valve repair systems that have an intended use to repair and/or improve the function of native human heart valves by acting either on the valve apparatus or on the adjacent anatomy (e.g. ventricle, coronary sinus). 1.2 This document outlines an approach for verifying/validating the design and manufacture of a heart valve repair system through risk management. The selection of appropriate verification/validation tests and methods are derived from the risk assessment. The tests include assessments of the physical, chemical, biological, and mechanical properties of components and materials of heart valve repair systems. The tests also include preclinical in vivo evaluation and clinical investigation of the finished heart valve repair system to assess the safety and effectiveness of the heart valve repair system. NOTE For the purposes of this document, effectiveness endpoint includes clinical performance and benefits. 1.3 This document defines operational conditions and performance requirements for heart valve repair systems where adequate scientific and/or clinical evidence exists for their justification. 1.4 This document excludes Cardiac Resynchronization Therapy (CRT) devices, paravalvular leakage closure devices, systems that do not leave an implant in place (e.g. ablation, radio frequency annuloplasty), apical conduits and devices with components containing viable cells. This Standard also excludes materials not intended for repairing and/or improving the function of human heart valves according to its intended use (e.g. patch material and sutures used in general surgical practice). NOTE A rationale for the provisions of this document is given in Annex A.
Implants cardiovasculaires et circuits extra-corporels — Dispositifs de réparation de valves cardiaques
General Information
Standards Content (Sample)
INTERNATIONAL ISO
STANDARD 5910
First edition
2018-06
Cardiovascular implants and
extracorporeal systems — Cardiac
valve repair devices
Implants cardiovasculaires et circuits extra-corporels — Dispositifs de
réparation de valves cardiaques
Reference number
ISO 5910:2018(E)
©
ISO 2018
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ISO 5910:2018(E)
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© ISO 2018
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ISO 5910:2018(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviations.11
5 Fundamental requirements .12
5.1 General .12
5.2 Risk management .12
6 Device description .13
6.1 Intended use/Indication for use .13
6.2 Design inputs .13
6.2.1 General.13
6.2.2 Operational specifications .13
6.2.3 Functional, performance and safety requirements .14
6.2.4 Usability .15
6.2.5 Packaging, labelling, and sterilization .16
6.3 Design outputs .16
6.4 Design transfer (manufacturing verification/validation) .16
7 Design verification testing and analysis / Design validation .16
7.1 General requirements .16
7.2 In vitro assessment .16
7.2.1 General.16
7.2.2 Test articles, sample selection, test conditions and reporting requirements .17
7.2.3 Device material property assessment .18
7.2.4 Functional performance assessment .19
7.2.5 Device structural performance assessment .19
7.2.6 Device corrosion assessment .20
7.2.7 Delivery system design evaluation requirements .20
7.2.8 Visibility.20
7.2.9 Simulated use assessment .20
7.2.10 Human factors / Usability assessment .21
7.2.11 Device MRI safety .21
7.2.12 Design specific testing .21
7.3 Preclinical in vivo evaluation .21
7.3.1 General.21
7.3.2 Overall requirements .21
7.3.3 Methods .23
7.3.4 Test report .24
7.4 Clinical Investigations .24
7.4.1 General.24
7.4.2 Study considerations .25
7.4.3 Study endpoints .28
7.4.4 Ethical considerations .28
7.4.5 Distribution of subjects and investigators .28
7.4.6 Statistical considerations including sample size and duration .29
7.4.7 Patient selection criteria .31
7.4.8 Clinical data requirements .31
7.4.9 Clinical investigation analysis and reporting .34
7.4.10 Post-market clinical follow-up .34
Annex A (informative) Rationale for the provisions of this document .36
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ISO 5910:2018(E)
Annex B (informative) Examples of heart valve repair devices and delivery systems .39
Annex C (normative) Packaging .45
Annex D (normative) Product labels, instructions for use, and training .46
Annex E (normative) Sterilization .49
Annex F (informative) Heart valve repair system characteristics .50
Annex G (informative) Heart valve repair system hazards, associated failure modes and
evaluation methods .52
Annex H (informative) In vitro test guidelines for paediatric devices .63
Annex I (informative) Examples and definitions of some physical and material properties
of heart valve repair device components .65
Annex J (informative) Examples of standards applicable to testing of materials and
components of heart valve repair devices .79
Annex K (informative) Considerations for device material properties undergoing
alterations post implantation .85
Annex L (informative) Corrosion assessment .86
Annex M (informative) Guidelines for in vitro evaluation of functional performance of the
repair .89
Annex N (informative) Durability testing .95
Annex O (informative) Fatigue assessment .97
Annex P (informative) Preclinical in vivo evaluation .103
Annex Q (normative) Adverse event classification during clinical investigation .106
Annex R (informative) Imaging protocol .112
Annex S (informative) Clinical investigation endpoints for valve repair devices: Suggestions
for endpoints and their timing .116
Annex T (informative) Additional device design evaluation requirements .120
Annex U (informative) Guidelines for delivery system design evaluation .122
Bibliography .124
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ISO 5910:2018(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 voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following
URL: www .iso .org/iso/foreword .html.
This document was prepared by ISO/TC 150, Implants for surgery, Subcommittee SC 2, Cardiovascular
implants and extracorporeal systems.
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ISO 5910:2018(E)
Introduction
No heart valve repair device is ideal. Therefore, a group of engineers, scientists, and clinicians, experts
well aware of the problems associated with heart valve repair devices and their development, has
prepared this document. This document specifies types of tests, test methods, and requirements for
test apparatus. It requires documentation of test methods and results. This document 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 heart team in choosing a heart valve repair device, and
ensure that the device will be provided in a convenient and usable form. This document emphasizes
the need to specify and report types of in vitro testing, 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 requirements 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 document also covers important functional and
durability characteristics of heart valve repair devices and their accessories. This document does not
specify exact test methods for functional and durability testing but it offers guidelines for the test
apparatus.
This document should be revised, updated, and amended as knowledge and techniques in heart valve
repair device technology improve.
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INTERNATIONAL STANDARD ISO 5910:2018(E)
Cardiovascular implants and extracorporeal systems —
Cardiac valve repair devices
1 Scope
1.1 This document applies to all heart valve repair systems that have an intended use to repair and/
or improve the function of native human heart valves by acting either on the valve apparatus or on the
adjacent anatomy (e.g. ventricle, coronary sinus).
1.2 This document outlines an approach for verifying/validating the design and manufacture of a
heart valve repair system through risk management. The selection of appropriate verification/validation
tests and methods are derived from the risk assessment. The tests include assessments of the physical,
chemical, biological, and mechanical properties of components and materials of heart valve repair
systems. The tests also include preclinical in vivo evaluation and clinical investigation of the finished
heart valve repair system to assess the safety and effectiveness of the heart valve repair system.
NOTE For the purposes of this document, effectiveness endpoint includes clinical performance and benefits.
1.3 This document defines operational conditions and performance requirements for heart valve
repair systems where adequate scientific and/or clinical evidence exists for their justification.
1.4 This document excludes Cardiac Resynchronization Therapy (CRT) devices, paravalvular
leakage closure devices, systems that do not leave an implant in place (e.g. ablation, radio frequency
annuloplasty), apical conduits and devices with components containing viable cells. This Standard also
excludes materials not intended for repairing and/or improving the function of human heart valves
according to its intended use (e.g. patch material and sutures used in general surgical practice).
NOTE A rationale for the provisions of this document is given in Annex A.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 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, Sterilization of health-care products — Ethylene oxide — Requirements for the development,
validation and routine control of a sterilization process for medical devices
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 of
development, validation and routine control
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,
sterile barrier systems and packaging systems
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ISO 5910:2018(E)
ISO 11607-2, Packaging for terminally sterilized medical devices — Part 2: Validation requirements for
forming, sealing and assembly processes
ISO 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14160, Sterilization of health care products — Liquid chemical sterilizing agents for single-use medical
devices utilizing animal tissues and their derivatives — Requirements for characterization, development,
validation and routine control of a sterilization process for medical devices
ISO 14630, Non-active surgical implants — General requirements
ISO 14937, Sterilization of health care products — General requirements for characterization of a sterilizing
agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 15223-1, Medical devices — Symbols to be used with medical device labels, labelling and information to
be supplied — Part 1: General requirements
ISO 15223-2, Medical devices — Symbols to be used with medical device labels, labelling, and information
to be supplied — Part 2: Symbol development, selection and validation
ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories
ISO 17664, Processing of health care products — Information to be provided by the medical device
manufacturer for the processing of 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/TS 17665-2, Sterilization of health care products — Moist heat — Part 2: Guidance on the application
of ISO 17665-1
ISO/TS 17665-3, Sterilization of health care products — Moist heat — Part 3: Guidance on the designation
of a medical device to a product family and processing category for steam sterilization
ISO 22442-1, Medical devices utilizing animal tissues and their derivatives — Part 1: Application of risk
management
ISO 22442-2, Medical devices utilizing animal tissues and their derivatives — Part 2: Controls on sourcing,
collection and handling
ISO 22442-3, Medical devices utilizing animal tissues and their derivatives — Part 3: Validation of the
elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents
ISO/TR 22442-4, Medical devices utilizing animal tissues and their derivatives — Part 4: Principles for
elimination and/or inactivation of transmissible spongiform encephalopathy (TSE) agents and validation
assays for those processes
IEC 62366-1, Medical devices — Part 1: Application of usability engineering to medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— IEC Electropedia: available at http: //www .electropedia .org/
— ISO Online browsing platform: available at https: //www .iso .org/obp
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ISO 5910:2018(E)
NOTE Additional definitions can be found in the informative annexes.
3.1
abnormal use
act or omission of an act by the operator or user of a medical device as a result of conduct which is
beyond any means of risk control by the manufacturer
3.2
accessory
device-specific tool that is required to assist in the implantation and/or adjustment of the heart valve
repair device, excluding the delivery system
3.3
active comparator
active control
intervention generally accepted or demonstrated to be safe and effective for the condition of interest
that can be used as a basis of comparison of the safety and effectiveness of the heart valve repair device
Note 1 to entry: The active comparator is generally the standard of care for the condition.
3.4
actuarial analysis
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.
3.5
adverse event
AE
untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including
abnormal laboratory findings) in subjects, users or other persons, whether or not related to the heart
valve repair device implantation, adjustment or procedure
3.6
auxiliary device
device used during the procedure, not including accessories (e.g. sheath, guidewire) and delivery system
3.7
back pressure
differential pressure applied across the valve during the closed phase
3.8
body surface area
BSA
2
total surface area (m ) of the human body
Note 1 to entry: This can be calculated as the square root of product of the weight in kg times the height in cm
divided by 3 600. See Reference [30].
3.9
cardiac index
2 2
cardiac output (3.10) (CO, l/min) divided by the body surface area (3.8) (BSA, m ), with units l/min/m
3.10
cardiac output
CO
stroke volume multiplied by heart rate
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ISO 5910:2018(E)
3.11
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.
Key
X time
Y flowrate
1 forward flow volume
2 closing volume
3 leakage volume
Figure 1 — Schematic representation of flow waveform and regurgitant volumes for one cycle
3.12
coating
thin-film material that is applied to an element of a heart valve repair device to modify its properties
3.13
compliance
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ISO 5910:2018(E)
relationship between change in radius and change in pressure of a deformable tubular structure (e.g.
valve annulus, aorta, conduit), defined in this document as:
()rr−×100
21
C=×100%
rp×−()p
12 1
where
C is the compliance in units of % radial change/100 mmHg;
p is the diastolic pressure, in mmHg;
1
p is the systolic pressure, in mmHg;
2
r is the inner radius at p , in millimetres;
1 1
r is the inner radius at p , in millimetres.
2 2
Note 1 to entry: See Reference [7].
3.14
component-joining material
material, such as a suture, adhesive or welding compound, used to assemble the components of a heart
valve repair device, thereby becoming part of the implanted device
3.15
cycle
one complete sequence in the action of a heart valve under pulsatile flow conditions
3.16
cycle rate
number of complete cycles per unit of time, usually expressed as cycles per minute (cycles/min)
3.17
delivery system
system used to deliver, deploy, attach or adjust the device in the implant site
3.18
design validation
establishment by objective evidence that device specifications conform with user needs and intended
use(s) (3.34)
3.19
design verification
establishment by objective evidence that the design output meets the design input requirements
3.20
device embolisation
dislodgement from the intended and documented original position to an unintended and nontherapeutic
location
3.21
device failure
inability of a device to perform its intended function sufficient to cause a hazard
3.22
device migration
unintended movement or displacement of the device from its original position within the implant site,
without embolisation
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ISO 5910:2018(E)
3.23
effective orifice area
EOA
orifice area that has been derived from flow and pressure or velocity data
Note 1 to entry: For in vitro testing, EOA is defined as:
q
v
RMS
EOA=
Dp
51,6×
ρ
where
2
EOA is the effective orifice area (cm );
is the root mean square forward flow (ml/s) during the positive differential pressure period;
q
v
RMS
Δp is the mean pressure difference (measured during the positive different
...
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