ISO 5910:2024

Cardiovascular implants and extracorporeal systems - Cardiac valve repair devices

1.1 This document specifies an approach for verifying and validating the design and manufacture of a heart valve repair system through risk management. The selection of appropriate verification and 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 end point includes clinical performance and benefits. 1.2 This document defines operational conditions and performance requirements for heart valve repair systems where adequate scientific and/or clinical evidence exists for their justification. It also describes the labels and packaging of the device. 1.3 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). 1.4 This document does not apply to 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 document 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

• Status: Published
• Publication Date: 04-Jul-2024
• ICS: 11.040.40 - Implants for surgery, prosthetics and orthotics
• Technical Committee: ISO/TC 150/SC 2 - Cardiovascular implants and extracorporeal systems
• Drafting Committee: ISO/TC 150/SC 2/WG 1 - Cardiac valves
• Current Stage: 6060 - International Standard published
• Start Date: 05-Jul-2024
• Due Date: 06-May-2024
• Completion Date: 05-Jul-2024

Relations

• Revises: ISO 5910:2018 - Cardiovascular implants and extracorporeal systems - Cardiac valve repair devices
• Effective Date: 23-Apr-2020

Overview

ISO 5910:2024 - "Cardiovascular implants and extracorporeal systems - Cardiac valve repair devices" (Second edition, 2024) defines a risk‑based framework for the verification and validation of heart valve repair systems. The standard specifies how to select and justify tests and methods based on risk assessment and covers evaluations of physical, chemical, biological and mechanical properties, as well as preclinical in vivo studies and clinical investigations to demonstrate safety and effectiveness (where effectiveness includes clinical performance and benefits).

Key topics and technical requirements

• Risk management driven testing: Verification and validation activities (in vitro, preclinical, clinical) are selected according to documented risk assessment.
• Design inputs and outputs: Requirements for intended use, operational specifications, functional/performance/safety requirements, usability, packaging, labelling and sterilization.
• In vitro testing: Material properties, integrated durability/corrosion assessments, simulated use, MRI safety and device visibility considerations.
• Preclinical in vivo evaluation: Study planning, methods, reporting and additional evaluation considerations for ex vivo/in vivo models.
• Clinical investigations: Study design, endpoints (safety and effectiveness), ethical and statistical considerations, subject selection and post‑market clinical follow‑up.
• Manufacturing verification and validation: Design transfer, process validation and quality evidence for production.
• Normative and informative annexes: Guidance on packaging, labelling, sterilization, test platforms, hazard analysis, imaging, paediatric testing, durability and clinical end points.

Scope and exclusions

• Applies to heart valve repair systems intended to repair or improve native human valve function by acting on the valve apparatus or adjacent anatomy (e.g., ventricle, coronary sinus).
• Excludes CRT devices, paravalvular leakage closure devices, non‑implant procedures (e.g., ablation, RF annuloplasty), apical conduits, devices with viable cells and general surgical materials not intended for valve repair.

Practical applications - who uses ISO 5910:2024

• Medical device manufacturers developing cardiac valve repair devices and delivery systems (including transcatheter and robotically‑assisted systems).
• Regulatory and clinical affairs teams preparing preclinical and clinical evidence packages for approvals and CE/FDA submissions.
• R&D, design verification/validation and quality assurance professionals establishing test strategies, durability studies, biocompatibility and sterilization plans.
• Clinical investigators and hospitals conducting device trials and post‑market clinical follow‑up.

Related standards (context)

ISO 5910:2024 is used alongside other medical device standards and guidance covering biological evaluation, sterilization, imaging and medical device risk management. Refer to applicable national/regulatory guidance for harmonization with clinical and regulatory requirements.

Keywords: ISO 5910:2024, cardiac valve repair devices, heart valve repair systems, verification and validation, risk management, preclinical in vivo, clinical investigation, device durability, material properties, packaging, labelling.

Standards Content (Sample)

International
Standard
ISO 5910
Second edition
Cardiovascular implants and
2024-07
extracorporeal systems — Cardiac
valve repair devices
Implants cardiovasculaires et circuits extra-corporels —
Dispositifs de réparation de valves cardiaques
Reference number
© ISO 2024
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on
the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below
or ISO’s member body in the country of the requester.
ISO copyright office
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
Phone: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii
Contents Page
Foreword .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviated terms . 9
5 Fundamental requirements . 10
5.1 General .10
5.2 Risk management .10
6 Device design .10
6.1 Intended use and indication for use .10
6.2 Design inputs .10
6.2.1 General .10
6.2.2 Operational specifications .10
6.2.3 Functional, performance and safety requirements . 12
6.2.4 Usability . 13
6.2.5 Packaging, labelling and sterilization . 13
6.3 Design outputs . 13
6.4 Design transfer (manufacturing verification and validation) . 13
7 Design verification testing and analysis, and design validation . 14
7.1 General requirements .14
7.2 In vitro assessment.14
7.2.1 General .14
7.2.2 Test articles, sample selection, test conditions and reporting requirements .14
7.2.3 Device material property assessment . .16
7.2.4 Device durability assessment .17
7.2.5 Device corrosion assessment .17
7.2.6 Design specific testing .17
7.2.7 Visibility .17
7.2.8 Simulated use assessment .18
7.2.9 Human factors and usability assessment .18
7.2.10 Device MRI safety .18
7.3 Preclinical in vivo evaluation .18
7.3.1 General .18
7.3.2 Overall requirements .18
7.3.3 Methods . 20
7.3.4 Test report .21
7.4 Clinical investigations . 22
7.4.1 General . 22
7.4.2 Study considerations . 22
7.4.3 Study end points .24
7.4.4 Ethical considerations . 25
7.4.5 Distribution of subjects and investigators . 25
7.4.6 Statistical considerations including sample size and duration . 26
7.4.7 Patient selection criteria .27
7.4.8 Clinical data requirements . 28
7.4.9 Clinical investigation analysis and reporting . .31
7.4.10 Post-market clinical follow-up .31
8 Manufacturing verification and validation .32
Annex A (informative) Rationale for the provisions of this document .33
Annex B (informative) Types and examples of heart valve repair devices and delivery systems .36
Annex C (normative) Packaging .43

iii
Annex D (normative) Product labels, instructions for use and training .44
Annex E (normative) Sterilization . 47
Annex F (informative) Heart valve repair system characteristics .48
Annex G (informative) Example of a transcatheter heart valve repair system hazard analysis .50
Annex H (informative) In vitro test guidelines for paediatric devices .51
Annex I (informative) Identification of boundary conditions .54
Annex J (informative) Test platforms for in vitro testing .58
Annex K (informative) Considerations for device material properties undergoing alterations
post implantation .60
Annex L (informative) Corrosion assessment . 61
Annex M (informative) Durability assessment .64
Annex N (informative) Additional device design evaluation considerations .71
Annex O (normative) Delivery system design evaluation . 74
Annex P (informative) Preclinical ex vivo and in vivo evaluations . 76
Annex Q (normative) Adverse event classification during clinical investigation .80
Annex R (informative) Multimodality imaging of TAVr, TMVr and TTVr (pre-, peri- and post-
implantation) .86
Annex S (informative) Clinical investigation end points for valve repair devices: Suggestions
for end points and their timing .91
Bibliography .95

iv
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 document 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).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a)
patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent
rights in respect thereof. As of the date of publication of this document, ISO had not received notice of (a)
patent(s) which may be required to implement this document. However, implementers are cautioned that
this may not represent the latest information, which may be obtained from the patent database available at
http://www.iso.org/patents. ISO shall not be held responsible for identifying any or all such patent rights.
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and expressions
related to conformity assessment, as well as information about ISO's adherence to the World Trade
Organization (WTO) principles in the Technical Barriers to Trade (TBT), see www.iso.org/iso/foreword.html.
This document was prepared by ISO/TC 150, Implants for surgery, Subcommittee SC 2, Cardiovascular
implants and extracorporeal systems.
This second edition cancels and replaces the first edition (ISO 5910:2018), which has been technically
revised.
The main changes are as follows:
— requirements in 7.2.2.3 and an informative annex (Annex J) have been added for test platforms;
— requirements and the informative annex on functional performance assessment have been removed;
— fatigue and durability testing have been combined into integrated device assessment in 7.2.4 and
Annex M;
— the description of the types of heart valve repair devices, including the added section on robotically-
assisted systems, has been moved into Annex B;
— Annex G on hazard and failure modes and Annex R on clinical imaging have been extensively revised;
— pulsatile flow conditions for the paediatric population have been clarified in Annex H;
— Annex I on boundary conditions has been added;
— annexes on physical and material property definitions and material property testing have been removed;
— additional device design evaluation requirements have been included in Annex N;
— additional evaluation considerations for preclinical in vivo evaluations have been included in Annex P.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.

v
International Standard ISO 5910:2024(en)
Cardiovascular implants and extracorporeal systems —
Cardiac valve repair devices
1 Scope
1.1 This document specifies an approach for verifying and validating the design and manufacture of a
heart valve repair system through risk management. The selection of appropriate verification and 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 end point includes clinical performance and benefits.
1.2 This document defines operational conditions and performance requirements for heart valve repair
systems where adequate scientific and/or clinical evidence exists for their justification. It also describes the
labels and packaging of the device.
1.3 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).
1.4 This document does not apply to 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 document
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 10993-4, Biological evaluation of medical devices — Part 4: Selection of tests for interactions with blood
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
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 information to be supplied by the manufacturer — 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 17664-1, Processing of health care products — Information to be provided by the medical device
manufacturer for the processing of medical devices — Part 1: Critical and semi-critical 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 20417, Medical devices — Information to be supplied by the manufacturer
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
ASTM F1830, Standard Practice for Selection of Blood for In Vitro Evaluation of Blood Pumps
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.

ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
accessory
device-specific tool that is required to assist in the implantation and/or adjustment of the heart valve repair
device (3.25), excluding the delivery system (3.12)
3.2
active comparator
intervention (e.g. transcatheter or surgical valve repair or replacement) generally accepted as the standard
of care for the intended valve device indication that can be used as a basis of comparison for the safety (3.45)
and effectiveness of the heart valve repair device (3.25)
3.3
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 investigational medical
device and whether anticipated or unanticipated
Note 1 to entry: This definition includes events related to the investigational medical device or the active comparator (3.2).
Note 2 to entry: This definition includes events related to the procedures involved.
Note 3 to entry: For users or other persons, this definition is restricted to events related to the use of investigational
medical devices or comparators.
3.4
boundary condition
displacement, force, moment, pressure or constraint acting on an implanted valve repair device and/or
surrounding tissue
3.5
cardiac output
CO
stroke volume [i.e. volume of blood pumped by a ventricle during systolic duration (3.53)] multiplied by the
heart rate
3.6
coating
thin-film material that is applied to an element of a heart valve repair system (3.26) to modify its surface
physical or chemical properties
3.7
compliance
C
relationship between the change in radius and the change in pressure of a deformable tubular structure (e.g.
valve annulus, aorta, conduit), given as
()rr−×100
C= ×100%
rp×−()p
12 1
where
p is the diastolic pressure, in mmHg;
p is the systolic pressure, in mmHg;
r is the inner radius at p , in mm;
1 1
r is the inner radius at p , in mm
2 2
Note 1 to entry: Compliance is expressed as a percentage of radial change per 100 mmHg.
3.8
component-joining material
material, such as a suture, adhesive or welding compound, used to assemble the components of a heart valve
repair device (3.25), thereby becoming part of the implanted device
3.9
cycle
complete sequence in the action of a native or repaired heart valve under pulsatile flow conditions
3.10
cycle rate
beat rate
number of complete cycles (3.9) per unit of time
Note 1 to entry: The cycle rate is usually expressed as cycles per minute or beats per minute.
3.11
delivery approach
anatomical access used to deliver the implant (3.28) to the implant site (3.29) (e.g. transfemoral, transapical,
transseptal)
3.12
delivery system
catheter or other system used to deliver, deploy, attach or adjust the device in the implant site (3.29)
3.13
design validation
establishment by objective evidence that device specifications conform with user needs and intended
use(s) (3.31)
3.14
design verification
establishment by objective evidence that the design output meets the design input requirements
3.15
device embolization
dislodgement from the intended and documented original position to an unintended and nontherapeutic
location
3.16
device failure
inability of a device to perform its intended function
3.17
device migration
detectable movement or displacement of the implant (3.28) from its original position within the implant site
(3.29), without device embolization (3.15)

3.18
failure mode
mechanism of device failure (3.16)
EXAMPLE Support structure (3.52) fracture (3.22), calcification and prolapse.
3.19
fatigue
process of progressive localized permanent structural change occurring in a material subjected to conditions
that produces fluctuating stresses and strains at some point(s) and that can culminate in cracks or complete
fracture (3.22) after a sufficient number of fluctuations
3.20
follow-up
continued assessment of subjects who have received the heart valve repair device (3.25)
3.21
forward flow volume
volume of flow ejected through the repaired heart valve in the forward direction
3.22
fracture
complete separation of any part of the heart valve repair device (3.25) that was previously intact
3.23
harm
injury or damage to the health of people, or damage to property or the environment
[SOURCE: ISO/IEC Guide 51:2014, 3.1]
3.24
hazard
potential source of harm (3.23)
[SOURCE: ISO/IEC Guide 51:2014, 3.2]
3.25
heart valve repair device
implant (3.28) intended to 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)
Note 1 to entry: See examples of heart valve repair devices in Annex B.
3.26
heart valve repair system
set of elements provided to repair the native heart valve, consisting of the heart valve repair device (3.25),
delivery system (3.12), accessories (3.1) as applicable, packaging, labelling and instructions
3.27
imaging modality
method used to visualize and assess native anatomy and/or device position, and geometry and/or function
3.28
implant
device placed surgically or non-surgically into the human body and intended to remain in place after the
procedure
3.29
implant site
intended location of heart valve repair device (3.25) implantation or deployment

3.30
indication for use
clinical condition of the patient population that the heart valve repair device (3.25) is intended to treat or improve
3.31
intended use
use of a product or process according to the specifications, instructions and information provided by the
manufacturer
3.32
linearized rate
total number of events divided by the total time under evaluation
Note 1 to entry: Generally, linearized rate is expressed in terms of percent per patient year.
3.33
loading
process to affix, attach or insert a repair device component onto or into a delivery system (3.12)
3.34
mean arterial pressure
time-averaged arithmetic mean value of the arterial pressure during one cycle (3.9)
3.35
non-structural dysfunction
abnormality extrinsic to the heart valve repair device (3.25) that results in abnormal function of the device
or causes clinical symptoms
EXAMPLE Entrapment by pannus (3.36), tissue or suture; paravalvular leak; inappropriate sizing or positioning,
residual leak or obstruction after implantation and clinically important haemolytic anaemia. This definition excludes
infection or thrombosis of the heart valve repair device and intrinsic factors, which cause structural native valve
deterioration (3.51).
3.36
pannus
ingrowth of tissue onto the heart valve repair device (3.25) which can interfere with normal functioning
3.37
pull-out testing
testing for a situation in which the suture or anchoring device remains structurally intact but tears through
the tissue in which it is implanted
3.38
reference device
heart valve substitute or heart valve repair device (3.25) with known clinical history used for comparative
preclinical and clinical evaluations
3.39
regurgitant volume
volume of fluid that flows through a repaired heart valve in the reverse direction during one cycle (3.9)
3.40
repositioning
intentional change of implant (3.28) position of a partially or fully deployed heart valve repair device (3.25) via
a surgical or transcatheter technique, possibly requiring full or partial removal or recapturing of the device
3.41
retrieval
removal of a partially or fully deployed heart valve repair device (3.25) via a surgical or transcatheter
technique
3.42
risk
combination of the probability of occurrence of harm (3.23) and the severity (3.48) of that harm
[SOURCE: ISO 14971:2019, 3.18]
3.43
risk analysis
systematic use of available information to identify hazards (3.24) and to estimate the associated risks (3.42)
[SOURCE: ISO 14971:2019, 3.19]
3.44
risk assessment
overall process comprising a risk analysis (3.43) and a risk (3.42) evaluation
[SOURCE: ISO 14971:2019, 3.20]
3.45
safety
freedom from unacceptable risk (3.42)
[SOURCE: ISO 14971:2019, 3.26]
3.46
serious adverse device effect
SADE
adverse effect of the device that has resulted in any of the consequences characteristic of a serious adverse
event (3.47)
Note 1 to entry: Planned hospitalization for a pre-existing condition or a procedure required by the clinical
investigation plan, without serious deterioration in health, is not considered a serious adverse event.
3.47
serious adverse event
SAE
adverse event (3.3) that leads to any of the following
a) death,
b) serious deterioration in the health of the subject, users or other persons, as defined by one or more of
the following:
1) a life-threatening illness or injury, or
2) a permanent impairment of a body structure or a body function including chronic diseases, or
3) in-patient or prolonged hospitalization, or
4) medical or surgical intervention to prevent life-threatening illness or injury, or permanent
impairment to a body structure or a body function,
c) foetal distress, foetal death, a congenital abnormality, or birth defect including physical or mental
impairment
3.48
severity
measure of the possible consequences of a hazard (3.24)
[SOURCE: ISO 14971:2019, 3.27]

3.49
sterility assurance level
SAL
probability of a single viable microorganism occurring on an item after sterilization (3.50)
Note 1 to entry: Sterility assurance level is expressed as the negative exponent to the base 10.
[SOURCE: ISO 11139:2018, 3.275]
3.50
sterilization
validated process used to render a 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.
[SOURCE: ISO 11139:2018, 3.277]
3.51
structural native valve dysfunction
structural native valve deterioration
dysfunction or deterioration intrinsic to the native valve, including calcification, leaflet fibrosis, leaflet tear
or flail, resulting in stenosis or regurgitation
3.52
support structure
load bearing structural component of a heart valve repair device (3.25)
3.53
systolic duration
portion of cardiac cycle (3.9) time corresponding to ventricular contraction
Note 1 to entry: For in vitro testing, systolic duration corresponds to the duration of forward flow in a cardiac cycle (3.9).
3.54
thromboembolism
embolic event involving a clot(s) that occurs in the absence of infection
Note 1 to entry: Thromboembolism can be manifested by a neurological event or an embolic event to another organ or
limb (e.g. ocular, coronary, mesenteric, femoral).
3.55
total product life cycle
period of time over which a product is developed, brought to market and eventually removed from the market
3.56
usability
characteristic of the user interface that facilitates use and thereby establishes effectiveness, efficiency, ease
of user learning and user satisfaction in the intended use (3.31) environment
[SOURCE: IEC 62366-1:2015, 3.16]
3.57
use error
act or omission of an act that results in a different medical device response than intended by the manufacturer
or expected by the user
EXAMPLE Incorrect sizing, suboptimal positioning, structural distortion of the device.
Note 1 to entry: An unexpected physiological response of the patient is not by itself considered a use error.

4 Abbreviated terms
For the purposes of this document, the following abbreviated terms apply.
ADE adverse device effect
AE adverse event
CMR cardiac magnetic resonance
CO cardiac output
CT computed tomography
CIP clinical investigation plan
CFD computational fluid dynamics
DIC disseminated intravascular coagulation
DPIV digital particle image velocimetry
DSMB data safety monitoring board
ECG electrocardiogram
EOA effective orifice area
EROA effective regurgitant orifice area
EuroSCORE European System for Cardiac Operative Risk Evaluation
FEA finite element analysis
FWHM full width at half maximum
GCP good clinical practice
HIT heparin-induced thrombocytopenia
ICE intra cardiac echocardiography
IFU instructions for use
INR international normalized ratio
LV left ventricle, left ventricular
LVAD left ventricular assist device
MACE major adverse cardiac events
MAP mean arterial pressure
MRI magnetic resonance imaging
NYHA New York Heart Association
PCI percutaneous coronary intervention
PET positron emission tomography

PMCF post-market clinical follow-up
SADE serious adverse device effect
SAE serious adverse event
SPECT single photon emission tomography
SSFP steady-state free precession
STS-PROM society of thoracic surgeons predicted risk of mortality
TAVr transcatheter aortic valve repair
TEE transoesophageal echocardiography
TMVr transcatheter mitral valve repair
TTE transthoracic echocardiography
TTVr transcatheter tricuspid valve repair
5 Fundamental requirements
5.1 General
The manufacturer shall determine, at all stages of the total product life cycle, the acceptability of the product
for clinical use.
5.2 Risk management
Risk management is the essential element for design and verification of medical devices. A risk-based
methodology challenges the manufacturer to continually evaluate known and theoretical risks of the
device, to develop the most appropriate methods for mitigating the risks of the device, and to implement the
appropriate test and analysis methods to demonstrate that the risks have been mitigated. The manufacturer
shall implement a risk management process in accordance with ISO 14971, and define and justify a risk
management programme, which should be specified in the risk management plan. Annex G provides a heart
valve repair system hazard analysis example.
6 Device design
6.1 Intended use and indication for use
The manufacturer shall identify the pathophysiological condition(s) to be treated, the intended patient
population and the intended claims.
6.2 Design inputs
6.2.1 General
The design attribute requirements of ISO 14630 shall apply where appropriate.
6.2.2 Operational specifications
The manufacturer shall define the operational specifications for the system, including the principles of
operation, intended device delivery approach if applicable, expected device lifetime, shelf life, shipping and
storage limits, and the physiological environment in which it is intended to function. The manufacturer shall

define all relevant dimensional parameters that will be required to accurately select the size of device to be
implanted, if applicable. Table 1 and Table 2 define the expected physiological parameters of the intended
adult patient population for heart valve repair devices for both normal and pathological patient conditions.
See Annex H for guidelines regarding suggested test conditions for the paediatric population.
Table 1 — Heart valve repair device operational environment for the left side of the heart — Adult
population
Parameter General condition
Surrounding medium Human heart and human blood
Temperature 34 °C to 42 °C
Heart rate 30 beat/min to 200 beat/min
Cardiac output 3 l/min to 15 l/min
Forward flow volume 25 ml to 100 ml
a
Patient condition Aortic peak systolic Aortic end diastolic Peak differential pressure across closed valve
pressure pressure
ΔP ΔP
A M
mmHg mmHg mmHg mmHg
Normotensive 90 to 139 60 to 89 80 to 114 90 to 139
Hypotensive <90 <60 <80 <90
Mild hypertensive 140 to 159 90 to 99 115 to 129 140 to 159
Moderate hypertensive 160 to 179 100 to 109 130 to 144 160 to 179
Severe hypertensive 180 to 209 110 to 119 145 to 164 180 to 209
Very severe hypertensive ≥210 ≥120 ≥165 ≥210
Key
ΔP peak differential pressure across closed aortic valve
A
ΔP peak differential pressure across closed mitral valve
M
a
Peak differential pressure across closed aortic and mitral valves estimated using the following relationships:
— ΔP ≈ pressure associated with dicrotic notch assuming LV pressure is zero ≈ aortic end diastolic pressure + 1/2 (aortic peak systolic pressure – aortic end
A
diastolic pressure);
— ΔP is estimated to be equivalent to the aortic peak systolic pressure.
M
Pressure values were obtained from References [32] and [33]).
Table 2 — Heart valve repair device operational environment for the right side of the heart — Adult
population
Parameter General condition
Surrounding medium Human heart and human blood
Temperature 34 °C to 42 °C
Heart rate 30 beat/min to 200 beat/min
Cardiac output 3 l/min to 15 l/min
Forward flow volume 25 ml to 100 ml
a
Patient condition Pulmonary artery peak Pulmonary artery end Peak differential pressure across closed valve
systolic pressure diastolic pressure
ΔP ΔP
P T
mmHg mmHg mmHg mmHg
Normotensive 18 to 34 8 to 14 13 to 27 18 to 34
Hypotensive <18 <8 <13 <18
Mild hypertensive 35 to 49 15 to 19 28 to 34 35 to 49
Key
ΔP peak differential pressure across closed pulmonary valve
P
ΔP peak differential pressure across closed tricuspid valve
T
a
Peak differential pressure across closed pulmonary and tricuspid valves estimated using the following relationships:
— ΔP ≈ pressure associated with dicrotic notch assuming RV pressure is zero ≈ pulmonary artery end diastolic pressure + 1/2 (right ventricle peak systolic
P
pressure – pulmonary artery end diastolic pressure);
— ΔP is estimated to be equivalent to pulmonary artery peak systolic pressure.
T
TTabablele 2 2 ((ccoonnttiinnueuedd))
Parameter General condition
Moderate hypertensive 50 to 59 20 to 24 35 to 42 50 to 59
Severe hypertensive 60 to 84 25 to 34 43 to 59 60 to 84
Very severe hypertensive ≥85 ≥35 ≥60 ≥85
Key
ΔP peak differential pressure across closed pulmonary valve
P
ΔP peak differential pressure across closed tricuspid valve
T
a
Peak differential pressure across closed pulmonary and tricuspid valves estimated using the following relationships:
— ΔP ≈ pressure associated with dicrotic notch assuming RV pressure is zero ≈ pulmonary artery end diastolic pressure + 1/2 (right ventricle peak systolic
P
pressure – pulmonary artery end diastolic pressure);
— ΔP is estimated to be equivalent to pulmonary artery peak systolic pressure.
T
6.2.3 Functional, performance and safety requirements
6.2.3.1 General
The manufacturer shall establish (i.e. define, document and implement) the functional, performance and
safety requirements of the heart valve repair system. With valve replacement devices, haemodynamic
performance and those adverse events which are directly valve-related can be measured and reasonably
attributed predominantly to the device. In contrast, because valve repair devices modify the native valve
or its function, leaving the native valve leaflets in place, haemodynamic and clinical performance including
adverse events can also depend on factors relating to the native valve and factors other than the device
itself. See Clause B.2 for examples of such factors.
6.2.3.2 Implantable device
The intended performance of the heart valve repair device shall take into consideration at least the following:
a) the ability to re
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