EN ISO 25539-2:2012

SLOVENSKI STANDARD
01-marec-2013
1DGRPHãþD
SIST EN ISO 25539-2:2009
SIST EN ISO 25539-2:2009/AC:2011
9VDGNLLPSODQWDWL]DVUFHLQRåLOMH=QRWUDMåLOQLSULSRPRþNLGHOäLOQHRSRUQLFH
VWHQW,62
Cardiovascular implants - Endovascular devices - Part 2: Vascular stents (ISO 25539-
2:2012)
Kardiovaskuläre Implantate - Endovaskuläre Implantate - Teil 2: Gefäßstents (ISO 25539
-2:2012)
Implants cardiovasculaires - Dispositifs endovasculaires - Partie 2: Endoprothèses
vasculaires (ISO 25539-2:2012)
Ta slovenski standard je istoveten z: EN ISO 25539-2:2012
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 25539-2
NORME EUROPÉENNE
EUROPÄISCHE NORM
December 2012
ICS 11.040.40 Supersedes EN ISO 25539-2:2009
English Version
Cardiovascular implants - Endovascular devices - Part 2:
Vascular stents (ISO 25539-2:2012)
Implants cardiovasculaires - Dispositifs endovasculaires - Kardiovaskuläre Implantate - Endovaskuläre Implantate -
Partie 2: Endoprothèses vasculaires (ISO 25539-2:2012) Teil 2: Gefäßstents (ISO 25539-2:2012)
This European Standard was approved by CEN on 30 November 2012.

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
© 2012 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 25539-2:2012: 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 25539-2:2012) 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 June 2013, and conflicting national standards shall be withdrawn at
the latest by June 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 supersedes EN ISO 25539-2:2009.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive.
For relationship with EU Directive, see informative Annex ZA, which is an integral part of this document.
According to the CEN/CENELEC Internal Regulations, the national standards organisations 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 25539-2:2012 has been approved by CEN as a EN ISO 25539-2:2012 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 Directive 93/42/EEC and this European Standard
Clause(s)/sub-clause(s) of Essential Requirements (ERs) of Qualifying remarks/notes
this European Standard Directive 93/42/EEC
6,8,10 and 12 7.2
6.3 and 7 7.3
st
6 7.5 1 sentence
6 and 7 7.6
7 8.2
12.1.5 8.3
11.1 8.4
11.2 8.5
nd
6 and 7 9.2, 2 indent
12.2.2 13.3 a)
12.2.2 13.3 b)
12.2.2 13.3 c)
12.2.2 13.3 d)
12.2.2 13.3 e)
12.2.2 13.3 f)
12.2.2 13.3 i)
12.2.2 13.3 k)
12.2.2 13.3 m)
5 13.5
12.3.2 13.6 g)
12.3.2 13.6 k)
12.3.2 13.6 q)
WARNING: Other requirements and other EU Directives may be applicable to the products falling within the
scope of this standard.
INTERNATIONAL ISO
STANDARD 25539-2
Second edition
2012-12-01
Cardiovascular implants — Endovascular
devices — Part 2: Vascular stents
Part 2:
Vascular stent
Implants cardiovasculaires — Dispositifs endovasculaires —
Partie 2: Endoprothèses vasculaires
Reference number
ISO 25539-2:2012(E)
©
ISO 2012
ISO 25539-2:2012(E)
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,
electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or ISO’s
member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2012 – All rights reserved

ISO 25539-2:2012(E)
Contents Page
Foreword .iv
Introduction . v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 General requirements . 4
4.1 Classification . 4
4.2 Size . 4
4.3 Intended clinical use designation . 5
5 Intended performance . 5
6 Design attributes . 5
6.1 General . 5
6.2 Delivery system and stent system . 6
6.3 Implant . 6
7 Materials . 7
8 Design evaluation . 7
8.1 General . 7
8.2 Sampling . 8
8.3 Conditioning of test samples . 8
8.4 Reporting . 8
8.5 Delivery system and stent system . 9
8.6 Stent .15
8.7 Preclinical in vivo evaluation .23
8.8 Clinical evaluation .27
9 Post-market surveillance .30
10 Manufacturing .30
11 Sterilization .30
11.1 Products supplied sterile .30
11.2 Products supplied non-sterile .31
11.3 Sterilization residuals .31
12 Packaging .31
12.1 Protection from damage in storage and transport .31
12.2 Marking .31
12.3 Information supplied by the manufacturer .32
Annex A (informative) Attributes of endovascular devices — Vascular stents — Technical and
clinical consideration .34
Annex B (informative) Bench and analytical tests .41
Annex C (informative) Definitions of reportable clinical events .45
Annex D (informative) Test methods .48
Annex E (informative) Supplement to fatigue durability test analytical approach .85
Bibliography .88
ISO 25539-2:2012(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 25539-2 was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This second edition cancels and replaces the first edition (ISO 25539-2:2008), of which it constitutes a minor
revision. This minor revision updates the normative references and provides minor editorial changes to Clause 8
and Annex D for clarification.
ISO 25539 consists of the following parts, under the general title Cardiovascular implants — Endovascular devices:
— Part 1: Endovascular prostheses
— Part 2: Vascular stents
— Part 3: Vena cava filters
iv © ISO 2012 – All rights reserved

ISO 25539-2:2012(E)
Introduction
This part of ISO 25539 has been prepared in order to provide minimum requirements for endovascular devices
and the methods of test that will enable their evaluation. It is the second part of a three-part standard. ISO 25539-1
addresses endovascular prostheses and ISO 25539-3 addresses vena cava filters. ISO/TS 15539, from which
this part of ISO 25539 is derived, serves as a rationale for the requirements of this part of ISO 25539. The
Technical Specification ISO/TS 15539 was developed by first identifying the design requirements for these
devices and listing the potential device and clinical failure modes. Tests were then identified to address each of
the failure modes. The requirements provided in this part of ISO 25539 are based on that assessment.
INTERNATIONAL STANDARD ISO 25539-2:2012(E)
Cardiovascular implants — Endovascular devices —
Part 2:
Vascular stents
1 Scope
1.1 This part of ISO 25539 specifies requirements for vascular stents, based upon current medical
knowledge. With regard to safety, it gives requirements for intended performance, design attributes, materials,
design evaluation, manufacturing, sterilization, packaging and information supplied by the manufacturer. It
should be considered as a supplement to ISO 14630, which specifies general requirements for the performance
of non-active surgical implants.
NOTE Due to the variations in the design of implants covered by this part of ISO 25539 and in some cases due to
the relatively recent development of some of these implants (e.g. bioabsorbable stents, polymeric stents), acceptable
standardized in vitro tests and clinical results are not always available. As further scientific and clinical data become
available, appropriate revision of this part of ISO 25539 will be necessary.
1.2 The scope of this part of ISO 25539 includes vascular stents used to treat vascular lesions or stenoses,
or other vascular abnormalities. These devices might or might not incorporate surface modifications of the stent
such as drug and/or other coatings. Stents covered with materials that significantly modify the permeability of
the uncovered stent are within the scope of ISO 25539-1. The stent design might dictate the need to address
functional requirements identified in both ISO 25539-1 and this part of ISO 25539.
1.3 Delivery systems are included in this part of ISO 25539 if they comprise an integral component of the
deployment of the vascular stent.
1.4 Procedures and devices used prior to the introduction of the vascular stent, such as balloon angioplasty
devices, are excluded from the scope of this part of ISO 25539.
1.5 Some pharmacological aspects of drug-eluting stents are addressed in this part of ISO 25539, but this
part of ISO 25539 is not comprehensive with respect to the pharmacological evaluation of drug-eluting stents.
1.6 Degradation and other time-dependent aspects of bioabsorbable and polymeric stents and coatings
are not addressed by this part of ISO 25539.
1.7 With the exception of sterilization, this part of ISO 25539 does not address requirements for the
evaluation of animal tissue products.
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 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 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 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials, sterile
barrier systems and packaging systems
ISO 25539-2:2012(E)
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 m 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 14971:2007, 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
3 Terms and definitions
For the purposes of this document, the terms and definitions in ISO 14630 and the following apply.
NOTE Bench and analytical tests are described in Annex B. Reportable clinical events are defined in Annex C.
3.1
balloon-assisted deployment
use of a balloon to facilitate the complete deployment (or expansion) of a self-expanding stent
3.2
balloon winging
cross-sectional shape of the balloon when deflated which can cause problems during withdrawal
NOTE Examples include stent migration, damage to host vessel or balloon, and inability to remove the balloon.
3.3
delivery system
system or mechanism used to deliver the stent to the targeted position and to deploy the stent
NOTE The delivery system is removed after stent placement. Examples of delivery systems include balloon catheters
or mechanically activated systems.
3.4
determine
to quantitatively appraise or analyse
NOTE Also see evaluate (3.8).
3.5
dogboning
dumbbell-shaped balloon observed during stent deployment when the unconstrained ends of the balloon
expand beyond the dilated stent outer diameter
3.6
coating
organic or inorganic material, other than living cells, intentionally applied by a manufacturer to a substrate
NOTE This coating can be intended to be permanent or temporary, and can be applied to the external and/or
internal surface.
2 © ISO 2012 – All rights reserved

ISO 25539-2:2012(E)
3.7
drug content
amount of drug present on the surface(s) of a coating, as part of a coating or within the stent
3.8
evaluate
to qualitatively appraise or analyse
NOTE Also see determine (3.4).
3.9
lumen reduction
reduction of diameter or cross sectional area as observed by imaging
3.10
reportable clinical events
complications, failures or device-related observations, including all adverse events and adverse device effects,
that might be observed with clinical use of the stent system
NOTE Examples are listed in Annex C. These events might not have clinical significance and might not be attributable
to the device.
3.11
stent configuration
stent shape (e.g. cylindrical, tapered, flared, coiled, segmented, bifurcated)
3.12
stent outer surface area
contact area between the stent and the vessel
3.13
stent-free surface area
percentage of surface area of cylinder formed by the implant frame, which is not covered by implant material
3.14
stent system
vascular stent and its delivery system or a vascular stent mounted on the delivery balloon as specified in the
instructions for use (IFU)
3.15
vascular stent
stent
implant
transluminally placed balloon-expandable or self-expanding implant, which is used to treat vascular lesions by
providing a mechanical support after deployment to maintain or restore vessel integrity
NOTE 1 Stents can or cannot incorporate surface modifications of the stent such as drug and/or other coatings.
NOTE 2 The following stent types are within the scope of this part of ISO 25539.
3.15.1
articulated stent
stent constructed of segments with distinct connections
3.15.2
bare stent
stent without a coating or covering
NOTE Bare stents can be constructed of single or multiple materials.
3.15.3
bioabsorbable stent
stent that is designed to be a temporary structure without requiring explantation
ISO 25539-2:2012(E)
3.15.4
balloon-expandable stent
stent where the diameter is increased from its pre-deployed size to its post-deployed size with the aid of a
balloon catheter
3.15.5
coated stent
stent with a surface layer of an additional material(s) that does not provide significant (e.g. more than 5 %)
structural support or appreciably reduce the permeability or stent-free surface area of the bare stent
3.15.6
composite stent
stent consisting of more than one material or material compound that provides significant (e.g. more than 5 %)
overall structural support upon deployment
3.15.7
covered stent
stent covered with an additional material(s) that appreciably reduces the permeability and/or eliminates the
stent-free surface area of the bare stent
NOTE Covered stents are within the scope of ISO 25539-1. The stent design might dictate the need to address
functional requirements identified in both ISO 25539-1 and this part of ISO 25539.
3.15.8
drug-eluting stent
DES
stent that delivers a drug(s) over time
3.15.9
self-expanding stent
stent where the diameter increases from its pre-deployed size to its post-deployed size when released from the
delivery mechanism in absence of balloon inflation or other mechanical assistance
NOTE Self-expanding stents are within the scope of ISO 25539-1. The stent design might dictate the need to address
functional requirements identified in both ISO 25539-1 and this part of ISO 25539.
4 General requirements
4.1 Classification
A stent shall be designated by its configuration (see 3.11), type (see 3.15), materials of construction, and any
surface modifications, coatings, and/or drugs.
4.2 Size
The size of a stent shall be designated by the following characteristics:
a) external diameter;
1) self-expanding:
i) unconstrained external diameter of the device, expressed in millimetres;
ii) intended vessel lumen diameter range, expressed in millimetres;
2) balloon expandable: range of intended expanded internal diameters;
b) minimum and maximum usable length, expressed in millimetres or centimetres.
4 © ISO 2012 – All rights reserved

ISO 25539-2:2012(E)
4.3 Intended clinical use designation
The intended clinical use shall be designated by one or more of the following:
a) abdominal aorta;
b) arterio-venous shunt for vascular access;
c) carotid;
d) coronary;
e) femoral;
f) iliac;
g) popliteal;
h) renal;
i) thoracic aorta;
j) thoraco-abdominal aorta;
k) tibial;
l) other arterial vessels to be specified;
m) other venous vessels to be specified.
5 Intended performance
The requirements for intended performance specified in ISO 14630:2012, Clause 4, shall apply.
6 Design attributes
6.1 General
The requirements for design attributes of ISO 14630:2012, Clause 5, apply. In addition, the following shall be
taken into account:
a) oxidation-potential, the possibility of crevice corrosion, passivation over the relevant parts;
b) fretting, galvanic and pitting corrosion;
c) interface between implant and body:
1) fixation hooks, if present;
2) relative movement between stent and tissue;
3) forces exerted by the stent on the surrounding tissue;
4) forces required to deform the stent if the deformation is permanent;
d) expected ingrowth, penetration, perforation, tilting and migration; introduction and delivery systems.
[14]
NOTE These additional items are adapted from Clause 5 of EN 12006-3:1998 .
The design attributes for vascular stents (with or without delivery system) are listed in Table A.2 with reference
to the test sections for the evaluation of the design (Clause 8). It is recognized that not all tests identified in a
ISO 25539-2:2012(E)
category will be necessary or practical for any given stent and/or delivery system. The tests considered and
the rationale for selection and/or waiving of tests shall be recorded.
6.2 Delivery system and stent system
The design attributes to meet the intended performance of the delivery system shall additionally take into
account at least the following:
a) the ability of the system to permit consistent, accurate and safe access to the intended location;
b) the ability of the system to permit consistent, accurate and safe deployment of the stent;
c) the ability of the system to permit consistent and safe withdrawal of the delivery system;
d) the compliance of the system with the requirements of ISO 10993-1 and appropriate other parts of the
ISO 10993 series of International Standards (biocompatibility);
e) the ability of the system to minimize blood loss (haemostasis);
f) the visibility of the system under fluoroscopy or other technologies.
6.3 Implant
6.3.1 Stent
The design attributes to meet the intended performance of the stent shall additionally take into account at least
the following:
a) the ability of the stent to be consistently, accurately and safely deployed;
b) the ability of the stent to ensure effective fixation and apposition in the intended location within the vasculature;
c) the ability of the stent to maintain adequate integrity;
d) the consistency of the stent dimensions and its design for compatibility for use in specified vessel diameters;
e) the ability of the stent to maintain adequate blood flow through the lumen (patency);
f) the compatibility of the stent with exposure to magnetic resonance imaging (MRI) fields;
g) the compliance of the stent with the requirements of ISO 10993-1 and appropriate other parts of the
ISO 10993 series of International Standards (biocompatibility);
h) the visibility of the stent under fluoroscopy or other technologies.
6.3.2 Coating
The design attributes to meet the intended performance of the coating shall additionally take into account at
least the following:
a) the ability of the coating to maintain adequate integrity over time according to design specifications
(e.g. freedom from significant delamination, flaps and bare spots);
b) the appropriate interaction between the coating and the stent (e.g. coating influenced corrosion of the substrate);
c) the ability of the coating to maintain adequate resistance to unintended particulate generation;
d) the conformance of the coating dimensions and other coating parameters (e.g. porosity, density, distribution)
to the design requirements;
e) the effect of MRI on the coating of a coated stent (e.g. heating).
6 © ISO 2012 – All rights reserved

ISO 25539-2:2012(E)
6.3.3 Drug
The design attributes to meet the intended performance of the stent if the coating is a drug or if a drug is
incorporated into the stent or coating shall additionally take into account at least the following:
a) the ability to reproducibly apply the desired drug type and amount to the stent;
b) the ability to release the desired amount of drug over the specified amount of time;
c) the conformance of the residual drug quantity to design specifications;
d) the freedom of the drug(s) from deleterious impurity and degradant levels at manufacture and with storage;
e) the appropriate interaction between the drug and the coating and/or the stent to which the drug is applied;
f) the effect of MRI on the drug of a drug-eluting stent (e.g. heating).
7 Materials
The requirements for materials of ISO 14630:2012, Clause 6, apply. Additional testing specific to certain
materials (e.g. metals, polymers, drugs) shall be performed to determine the appropriateness of the material
for use in the design. For example, Nitinol materials dependent on shape memory properties shall be subjected
to testing in order to assess transformation properties. In addition, for drug-eluting stents drug identity testing
shall be performed, including the identification of impurities and degradants. Electro-chemical potentials of
differing metals (stents, guidewires, other accessory devices) might require additional types of testing.
8 Design evaluation
8.1 General
The requirements for design evaluation of ISO 14630:2012, Clause 7, apply. A risk assessment shall be carried
out and the requirements of ISO 14971:2007, Clauses 4, 5, 6 and 7, shall apply.
Justification shall be provided for the properties not measured.
NOTE 1 All testing might not be appropriate for all stent system designs.
It is impossible to take into consideration all future and emerging technologies. The stent systems based on
these new technologies will need to be evaluated following the basic requirements of this part of ISO 25539.
Testing beyond the scope of this part of ISO 25539 might also be necessary in order to characterize these
stent systems. Consideration shall be given to the failure modes of the stent systems and their effects on the
performance of the implant in identifying the appropriate testing.
Whenever changes are made in materials, construction, configuration, application or processing methods, an
appropriate analysis of the potential impact of the change on the failure modes and performance of the stent
system shall be performed. Appropriate testing shall be conducted as deemed necessary.
The use of a control device for comparison should be considered in the evaluation of certain design attributes.
If overlapping of stents can be anticipated in clinical use (e.g. superficial femoral artery, coronary), integrity of
the stent under study in overlapping configurations should be evaluated, unless justification can be provided for
testing of individual stents. If overlapping with a different device is specifically indicated, testing should include
evaluation with the indicated device.
ISO 25539-2:2012(E)
Testing to establish the labelled shelf-life shall be conducted by repeating appropriate tests. Justification for the
selection of tests shall be provided. For drug-eluting stents, real time and accelerated testing conditions should
be used to define drug attributes for product shelf life.
1) [34] [35]
NOTE 2 Additional guidance for stability testing of drug products can be found in ICH Q1A (R2), ICH Q1B ,
[36]
and ICH Q1D .
8.2 Sampling
A sampling plan shall be utilized which will ensure that adequate representation of the data has been obtained
for each parameter measured. The design characteristics of the stent (including any drugs and/or coatings),
delivery system and stent system shall be verified to be representative of the devices to be released for
distribution, including all sizes, configurations and components.
The sampling shall fully represent the range of device designs and might not necessarily require the testing of
each size. The stent sizes selected for testing shall represent the worst case combination(s) of diameter and
length for each test. A rationale shall be provided for sample selection. It might be necessary to conduct an
assessment to identify the size(s) of the device with the greatest potential for failure.
Sampling shall ensure adequate representation of the expected variability in the manufacture of devices.
For those tests with specified confidence and reliability parameters, the sample size shall have a statistical
basis. For all tests, the number of samples shall be justified.
8.3 Conditioning of test samples
All samples shall be subjected to sterilization, including multiple sterilizations, if appropriate, unless justification
is provided for use of non-sterilized products.
Samples shall be subjected to conditions that are normally encountered which might affect the test results.
Conditioning might include loading the stent on or inside the delivery catheter, preconditioning of the stent
system as recommended in the instructions for use (IFU), single or multiple passes through an anatomical
model, and deployment of the stent.
A simulated physiological environment (e.g. a temperature-controlled water bath) shall be used when appropriate.
8.4 Reporting
For the purposes of this part of ISO 25539, reporting relates to requests from a national regulatory authority or
from a body responsible for assessing conformity.
The test report for the preclinical in vitro testing shall include an executive summary of all testing. This summary
should include identification of tests, with the rationale for the omission of any tests identified in Annex B
or the selection of alternative tests. The information provided in each test report should be based upon a
prospectively defined test protocol.
A summary of results, with acceptance criteria and any potential clinical significance of the results, should
be included and can be in tabular form. Consideration shall be given to the anatomical, physiological, and
morphological conditions of the intended use in establishing the acceptance criteria. Justification and clinical
applicability of acceptance criteria for each test shall be provided. A table of contents should be provided and
pages should be numbered sequentially.
Individual test reports should include the following information:
a) purpose: state the purpose of the test as it corresponds to this part of ISO 25539;
b) materials: list all materials (e.g. test articles with lot/serial numbers or other appropriate means of
traceability, equipment) used in performing the test, using figures and diagrams as appropriate;
1) International Conference on Harmonization guidelines.
8 © ISO 2012 – All rights reserved

ISO 25539-2:2012(E)
c) sampling: state the sampling plan, including the basis for and the number of samples tested; selection of
test articles shall be justified (e.g. sizes, conditioning);
d) acceptance criteria: state the acceptance criteria for the test results;
e) test method: describe in detail the method used to perform the test, including any prospectively defined
inspection procedures, and provide a justification for critical test parameters;
f) protocol deviations: describe any deviations and their potential significance on the interpretation of the results;
g) expression of results: describe testing results expressed in units as indicated in the test method;
h) conclusion: state conclusions, based on comparing results to acceptance criteria, including any potential
clinical significance of these results.
8.5 Delivery system and stent system
8.5.1 Ability to access
8.5.1.1 General
This covers the ability of the system to permit safe, consistent and accurate access to the intended location.
For estimating risks, the hazards to be considered include, but are not limited to, the following:
a) guidewire not crossing the lesion;
b) introducer and delivery system not matching the access site (i.e. size mismatch);
c) delivery system not advancing to target site;
d) embolism and air embolization;
e) stent dislodgement.
These hazards might result in reportable clinical events, including but not limited to the following:
— access failure;
— vascular trauma;
— neurological deficit;
— ischemia;
— spinal neurological deficit;
— embolization;
— procedural bleeding.
Testing shall include the following items listed in 8.5.1.2 to 8.5.1.13, as appropriate to the design of the stent system.
8.5.1.2 Bond strength
Determine the longitudinal bond strength between parts of the delivery system. All bonds shall remain intact
under recommended conditions of use. The results shall be evaluated in relation to the force(s) necessary to
access the intended location.
ISO 25539-2:2012(E)
8.5.1.3 Component dimension compatibility
Evaluate the dimensions of the stent system for compatibility with the dimensions of recommended accessories.
All components shall be dimensionally compatible. The need for contrast to be able to pass through the lumen
of the guide catheter or introducer with the stent system in place should be considered.
8.5.1.4 Dimensional verification
Determine the appropriate dimensions for conformance with design specifications.
8.5.1.5 Dislodgement force (pre-mounted balloon expandable stents)
Determine the force required to dislodge the premounted stent from the crimped position on the non-expanded
balloon and to completely separate the stent from the non-expanded balloon during clinical use.
8.5.1.6 Flex/kink
Evaluate the ability of the stent system to bend in order to accommodate the predetermined clinically relevant
radius or angle it will be required to negotiate during access and delivery.
8.5.1.7 Profile/diameter test
Determine the maximum diameter along sections of the stent system.
8.5.1.8 Pushability
Evaluate the ability of the stent system to be pushed or positioned by an operator without undesirable
bending or buckling.
8.5.1.9 Simulated use
Evaluate the performance of the stent system using a model(s) that simulate(s) the intended use conditions.
8.5.1.10 Torquability
Evaluate the ability of the stent system to provide sufficient rotation to the distal (leading) end to deliver the stent
within the anatomy, if appropriate for the intended clinical use.
8.5.1.11 Torsional bond strength
Determine the torque/rotation required to break joints and/or materials in the appropriate delivery system
components, if appropriate for the intended clinical use. The results shall be evaluated in relation to the torque
necessary to access the system.
8.5.1.12 Trackability
Evaluate the ability of the stent system to advance through the vessel to the target site using the recommended
accessories. Evaluate the potential for displacement of the guidewire from its intended position during the
advancement of the stent system, as appropriate for the intended use of the stent (e.g. loss of side-branch
access during stenting).
8.5.1.13 Visibility
Evaluate the ability to visualize the delivery system and/ or stent system during access using fluoroscopy. The
use of other technologies for visualization shall be justified.
10 © ISO 2012 – All rights reserved

ISO 25539-2:2012(E)
8.5.2 Ability to deploy
8.5.2.1 General
This covers the ability of the system to permit safe, consistent and accurate deployment of the stent.
For estimating risks, the hazards to be considered include, but are not limited to, the following:
a) inability to fully and properly deploy the stent;
b) stent dislodgement;
c) balloon failure (if applicable);
d) stent or delivery system damage;
e) inadequate visualization;
f) embolism and air embolization.
These hazards might result in reportable clinical events, including, but not limited to, the following:
— delivery system failure;
— deployment failure;
— spinal neurological deficit;
— neurological deficit;
— vascular trauma;
— ischemia;
— embolization;
— damage to stent;
— proce
...