EN 14299:2004

SLOVENSKI STANDARD
01-november-2004
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Non active surgical implants - Particular requirements for cardiac and vascular implants -
Specific requirements for arterial stents
Nichtaktive chirurgische Implantate - Besondere Anforderungen an Herz- und
Gefäßimplantate - Spezielle Anforderungen an Arterienstents
Implants chirurgicaux non actifs - Exigences particulieres s'appliquant aux implants
cardiaques et vasculaires - Exigences spécifiques relatives aux endoprotheses
artérielles
Ta slovenski standard je istoveten z: EN 14299:2004
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 14299
NORME EUROPÉENNE
EUROPÄISCHE NORM
May 2004
ICS 11.040.40
English version
Non active surgical implants - Particular requirements for cardiac
and vascular implants - Specific requirements for arterial stents
Implants chirurgicaux non actifs - Exigences particulières Nichtaktive chirurgische Implantate - Besondere
s'appliquant aux implants cardiaques et vasculaires - Anforderungen an Herz- und Gefäßimplantate - Spezielle
Exigences spécifiques relatives aux endoprothèses Anforderungen an Arterienstents
artérielles
This European Standard was approved by CEN on 2 February 2004.
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 Central Secretariat 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 Central Secretariat has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,
Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia,
Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2004 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN 14299:2004: E
worldwide for CEN national Members.

Contents
page
Foreword.3
Introduction.5
1 Scope .6
2 Normative references .6
3 Terms and definitions .7
4 Intended performance .9
5 Design attributes .9
6 Materials .9
7 Design evaluation .10
8 Manufacturing .26
9 Sterilization.26
10 Packaging.27
11 Information supplied by the manufacturer .27
Annex A (informative)  Cross reference of specific aims .29
Annex B (informative)  Definitions of reportable clinical events.33
Annex ZA (informative)  Clauses of this European Standard addressing essential
requirements or other provisions of EU Directives .37
Bibliography.38
Foreword
This document (EN 14299:2004) has been prepared by the Technical Committee CEN/TC 285
“Non-active surgical implants”, the secretariat of which is held by NEN.
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 November 2004, and conflicting national
standards shall be withdrawn at the latest by November 2004.
This document has been prepared under a mandate given to CEN by the Commission of the
European Community and the European Free Trade Association, and supports Essential
Requirements of EC Directive(s).
For relationship with the EC Council Directive 93/42/EEC of June 14, 1993. see informative
Annex ZA, which is an integral part of this document.
There are three levels of European Standards dealing with non-active surgical implants. These
are as follows, with level 1 being highest:
Level 1: General requirements for non-active surgical implants;
Level 2: Particular requirements for families of non-active surgical implants;
Level 3: Specific requirements for types of non-active surgical implants.
This standard is a level 3 standard and contains requirements that apply to specific types of
implants within a family.
The level 1 standard, EN ISO 14630, contains requirements that apply to all non-active surgical
implants. It also indicates that there are additional requirements in the level 2 and level 3
standards.
The level 2 standards apply to a more restricted set or family of implants such as those designed
for use in osteosynthesis, cardiovascular surgery, or joint replacement.
NOTE For cardiac and vascular implants three level 2 standards have been published:
EN 12006-1, Non-active surgical implants - Particular requirements for cardiac and vascular implants -
Part 1: Heart valve substitutes.
EN 12006-2, Non-active surgical implants - Particular requirements for cardiac and vascular implants -
Part 2: Vascular prostheses including cardiac valve conduits.
EN 12006-3, Non-active surgical implants - Particular requirements for cardiac and vascular implants -
Part 3: Endovascular devices.
To address all requirements, it is necessary to start with a standard of the lowest available level.
References to other European or International Standards can also be found in the Bibliography.
Annexes A and B are informative.
According to the CEN/CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Cyprus,
Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
Introduction
In addition to EN ISO 14630 and EN 12006-3 this European Standard provides minimum
requirements for sterile arterial stents and endovascular prostheses and the methods of test for
their evaluation.
1 Scope
This European Standard specifies specific requirements for arterial stents and endovascular
prostheses and their deployment intended to correct or compensate for a defect of an artery.
With regard to safety, this standard gives in addition to EN ISO 14630 and
EN 12006-3 specific requirements for intended performance, design attributes, materials, design
evaluation, manufacturing, sterilization, packaging and information supplied by the manufacturer.
This European Standard applies to arterial stents and endovascular prostheses used in the aorta,
cervical segments of cerebral arteries, coronary arteries, intra-cerebral arteries, peripheral
arteries, pulmonary arteries, supra-aortic arteries and visceral arteries. It also includes
endovascular prostheses used to treat aneurysms, arterial stenoses, or other vascular
abnormalities.
NOTE 1 Delivery systems are included in this standard if they comprise an integral component of the
deployment of the implant.
NOTE 2 Covered stents used as occluders are included in this standard.
2 Normative references
This European Standard incorporates by dated or undated reference, provisions from other
publications. These normative references are cited at the appropriate places in the text, and the
publications are listed hereafter. For dated references, subsequent amendments to or revisions of
any of these publications apply to this European Standard only when incorporated in it by
amendment or revision. For undated references the latest edition of the publication referred to
applies (including amendments).
EN ISO 10555-1:1996, Sterile, single-use intravascular catheters – Part 1: General requirements
(ISO 10555-1:1996).
EN ISO 10555-4:1997, Sterile, single-use intravascular catheters – Part 4: Balloon dilatation
catheters (ISO 10555-4:1996).
EN ISO 11070, Sterile single-use intravascular catheter introducers (ISO 11070:1998).
EN 12006-2:1998, Non-active surgical implants – Particular requirements for cardiac and
vascular implants – Part 2: Vascular prostheses including cardiac valve conduits.
EN 12006-3:1998, Non-active surgical implants – Particular requirements for cardiac and
vascular implants – Part 3: Endovascular devices.
EN ISO 14155-1, Clinical investigation of medical devices for human subjects – Part 1: General
requirements (ISO 14155-1:2003).
EN ISO 14155-2, Clinical investigation of medical devices for human subjects – Part 2: Clinical
investigation plans (ISO 14155-2:2003).
EN ISO 14630:1997, Non-active surgical implants – General requirements (ISO 14630:1997).
3 Terms and definitions
For the purposes of this European Standard, the terms and definitions given in EN 12006-3:1998
and the following apply.
3.1
arterial stent
implantable tubular structure which supports an arterial conduit. This includes endovascular
prostheses
3.2
bare stent
stent that is not covered or coated
3.3
cervical segments of cerebral arteries
extracranial segments of the internal carotid and vertebral arteries
3.4
crush resistance
ability of an implant to withstand load until permanent (or plastic) deformation or full collapse
occurs
3.5
delivery system
system or mechanism used to deliver the implant to the targeted position which is then removed
3.6
direct stenting
placement of the implant without prior balloon dilatation
3.7
dogboning
dumbbell-shaped deformity observed during direct stenting if the proximal and distal ends of the
balloon expand beyond the dilated implant diameter
3.8
endoleak
persistence of blood flow outside the lumen of an implant but within an aneurysm sac or adjacent
vascular segment being treated by the graft. Endoleaks are categorized as follows:
type I endoleak is periprosthetic and occurs at the proximal or the distal attachment zones;
type II endoleak is caused by retrograde flow from collateral arterial branches;
type III endoleak arises from a defect in the graft fabric, or inadequate seal or disconnection
of modular graft components;
type IV endoleak is due to graft permeability, often resulting in a generalized mild blush of
contrast medium within the aneurysm sac
3.9
endovascular prosthesis
transluminally placed vascular prosthesis, e.g. a stent graft, residing partially or completely within
a vascular conduit to form an internal bypass or shunt between sections of the vascular system
3.10
implant
arterial stent or endovascular prosthesis
3.11
implant free surface area
percentage of the surface area of the cylinder formed by the implant frame, which is not covered
by implant material
3.12
implant recoil
amount by which the diameter of an implant changes from its initial diameter when still on its fully
inflated delivery system to its relaxed final diameter after deflating the system, expressed as a
percentage of the diameter measured when still on the fully inflated delivery system
3.13
MRI compatibility
the implant is MRI compatible if, when used in a specified MRI environment:
it has been demonstrated not to significantly affect the quality of the diagnostic information;
and
the implant function is not affected by the MRI environment
3.14
nominal condition
diameter and length of the implant as stated by the manufacturer for the relaxed implant after
expansion
3.15
outer package
container for the unit package(s), designed to protect from damage due to storage and/or
transportation
3.16
patency
ability of an implant to maintain an open lumen following implantation
3.17
radial outward force (for self-expanding implants)
force exerted by a self-expanding implant as a function of the implant diameter
3.18
reference device
implant or delivery system chosen to compare methods and/or results for testing
3.19
self-expanding implant
implant where the diameter is increased from its pre-deployed size to its post-deployed size
without requiring plastic deformation
3.20
supra-aortic arteries
supra-aortic arteries begin at the aortic arch and extend up to the bifurcation of the carotid and
the take-off of the vertebral arteries. Within these boundaries are included all the arteries
supplying the head and the upper extremities: innominate artery, subclavian arteries and carotid
arteries
3.21
unit package
package intended to maintain sterility
3.22
visceral arteries
visceral arteries include the coeliac trunk and its branches, the renal arteries, the superior
mesenteric artery, the inferior mesenteric artery and the internal iliac arteries
4 Intended performance
The requirements of Clause 4 of EN ISO 14630:1997 apply.
5 Design attributes
The requirements of Clause 5 of EN 12006-3:1998 apply, together with the following:
The design attributes for implants (with or without delivery system) are listed in Table A.1 (see
Annex A) with reference to the test sections for the evaluation of the design (7.2. and 7.3). It is
recognized that not all tests identified in a category will be necessary or practical for any given
implant and/or delivery system. Furthermore, tests other than those mentioned in this standard
may be applicable to prove compliance with the Essential Requirements of the European Council
Directive 93/42/EEC of June 14, 1993. Therefore Table A.1 is a framework for the development of
an assessment programme and not a checklist. The tests considered and the rationale for
selection and/or waiving of tests shall be recorded.
6 Materials
6.1 General
The requirements of Clause 6 of EN ISO 14630:1997 apply.
NOTE 1 A stent delivery system should be considered as an external communicating device in contact
with circulating blood for less than 24 hours.
NOTE 2 The series EN ISO 10993 within ISO/TC 194 "biological evaluation of medical devices" is a work
in progress.
6.2 Corrosion
The susceptibility of the material(s) and the final product to corrosion shall be evaluated in an
appropriate environment.
7 Design evaluation
7.1 General
This evaluation shall address the relevant design attributes as listed in Annex A.
The requirements of Clause 7 of EN 12006-3:1998 apply together with the following:
If acceptance criteria are not specified, the manufacturer shall evaluate the acceptability of the
results against predetermined and justified criteria.
If no test method is described in this standard, a description of the justified test method, and
sample preparation used in the evaluation shall be documented by the manufacturer. The method
chosen, including the choice of the reference implant, shall be justified.
NOTE If it can be justified that sterilization has no effect on the characteristics of the implant or delivery
system that are under evaluation, the required tests can be carried out on non-sterilized implant or delivery
system.
7.2 Pre-clinical evaluation: Bench and analytical tests for implants
7.2.1 General
The relevant design attributes shall be tested in an environment which simulates the intended use
conditions (e.g. temperature, geometry). The rationale for the test conditions and sample size
selected shall be specified by the manufacturer. The assessment of the results against the
acceptance criteria shall be documented by the manufacturer.
7.2.2 Simulated use / conformability to vessel wall
The design attributes as identified in Annex A shall be evaluated using a model that simulates the
intended use conditions.
7.2.3 Dimensions
The requirements of Clause 7.2.1 of EN 12006-3:1998 apply, together will following:
In case of implants the length of the implant after expansion needs to be determined in nominal
conditions.
NOTE The inner diameter may be calculated from the outer diameter and the implant wall thickness.
Using an adequate measurement technique measure the outer diameters of the implant at each
end and in the middle in two perpendicular directions.
For each implant calculate the mean of all the diameters measured.
For a non-cylindrical implant (for example an oval or conical implant), the profile shall be
described.
In the case of implant designs where the length changes as a function of the expanded diameter,
the corresponding lengths and diameter shall be measured.
In the case of a self-expanding implant the expansion range (minimum and maximum diameter
after expansion) shall be measured.
The working range of the implant shall be documented. The test results shall be recorded and
shall be within the tolerances claimed by the manufacturer.
7.2.4 Visibility
The visibility of the implant, including under fluoroscopy, shall be determined and evaluated, and
the test conditions shall be documented. The implant shall be visible under validated imaging
techniques used clinically.
7.2.5 Crush resistance
For each nominal diameter and each implant configuration, the change in implant diameter shall
be measured as a function of circumferential applied pressure or radial force until permanent
deformation or full collapse occurs.
7.2.6 Radial outward force (for self-expanding implants)
For each nominal diameter the force exerted by the self-expanding implant shall be measured as
a function of the diameter of the implant or displacement, as appropriate to test method used.
7.2.7 Recoil for balloon expandable implants
The implant recoil shall be measured and express as a percentage of the initial diameter.
NOTE This test is appropriate for implants manufactured from a material that is plastically deformed
when the diameter of the implant is increased from its pre-deployed size to its post-deployed size by
mechanical means.
The test shall be performed without external stress to the implant.
The implant shall be mounted onto a balloon of a nominal size for which the implant is intended to
be used.
The balloon with the implant shall be inflated to the nominal pressure.
The size of the expanded implant on the inflated balloon shall be measured.
The balloon shall be deflated and the diameter of the implant shall be measured.
The measurement accuracy of the actual diameters shall be less than 1 % of the nominal
diameter.
The implant recoil is given by the following expression:
Im plant recoil (%) = [(Diameter  - Diameter )/Diameter ] · 100
inflated final inflated
where
Implant recoil = The amount by which the diameter of an implant changes from its initial
diameter when still on its fully inflated delivery system to its relaxed final diameter
after deflating the system, expressed as a percentage of the diameter measured
when still on the fully inflated delivery system.
Diameter = The outer diameter of the implant with the balloon fully inflated.
inflated
Diameter = The outer diameter of the implant in a stable condition after deflating the
final
balloon (when demonstrated that a stable minimum diameter is reached).
T he implant recoil shall be calculated for proximal, middle, and distal cross-sections for each
implant. If the expanded and recoiled implants are not circular and concentric, this shall be
explained with the recoil data provided. The average and standard deviation of implant recoil shall
be calculated for all data for each size of implant.
7.2.8 Fatigue testing
T he evaluation of the fatigue resistance of the implant shall demonstrate that the in vivo
conditions to which the implant may be exposed will not result in implant failure.
T he long-term dimensional and structural integrity of the implant shall be evaluated. This includes
the integrity of each single part of the implant and the connections and contact areas between
each other and to the regions intended to be in contact with the vessel. Tests shall be conducted
under conditions simulating in vivo radial, axial and other loads as appropriate.
Fatigue testing shall include in vitro testing of at least 380 million cycles (10 years equivalent). If
the intended implant life is less than 10 years, shorter duration fatigue testing may be appropriate
and shall be justified.
Cons tant and periodic stresses equivalent to physiologic load shall be applied to at least six
implants. The deformation of the implant under test shall be at least as great as under the
intended implant condition, simulating the worst-case physiological load. The test frequency shall
be chosen such that the diametric displacements of the implant remain within the required limits
for the duration of the test. The maximum testing frequency may be limited by the effects of the
strain rate on the mechanical properties of the materials. For example, at high frequency the
implant may not experience the intended displacement. Additionally, the test frequency may be
limited by the test equipment. Secondary harmonics may be introduced when testing at some
frequencies.
The implant size(s) and configurations to be evaluated shall be selected to represent the greatest
potential for fatigue failure and other failure modes being evaluated based upon appropriate
engineering analysis such as a stress/strain analysis.
The test of balloon-expandable implants may be conducted at room temperature. The tests of
thermo self-expanding implants shall be conducted at (37 – 2) °C.
The implant size(s) and test frequency selected shall be justified.
7.2.9 Strength
7.2.9.1 Burst strength, longitudinal tensile strength, factory anastomotic strength and
suture retention strength (when applicable) for implants
T he requirements of Clause 7.4 of EN 12006-2:1998 apply together with the following:
The tests shall be conducted on the finished product and separately on graft material if
appropriate.
7.2.9.2 Strength of implant/attachment system to graft bond (e.g. adhesie, sutures)
Evaluate the strength of the connection of the graft to the implant/attachment system.
7.2.9.3 Longitudinal tensile strength
The longitudinal tensile strength shall be determined to evaluate the force to separate bonded
components.
7.2.10 Evaluation of MRI compatibility
The manufacturer shall evaluate the MRI compatibility of the implant when used in a specified
MRI environment. The test conditions and test results shall be documented.
The manufacturer shall determine:
the extent to which magnetic resonance imaging affects the implants, e.g. heating,
movement of stents;
whether the implant will cause artefacts with magnetic resonance imaging due to distortion of
the magnetic field.
NOTE Literature references may substitute for actual data if adequately justified.
7.2.11 Implant free surface area
The manufacturer shall determine the free or open area of any uncovered region of the implant.
This shall be expressed as a percentage of the total area.
7.2.12 Permeability and Porosity
The requirements of Clause 8.2 of EN 12006-2:1998 apply to finished products.
Determine the porosity, water permeability, and water entry pressure, as appropriate to the
implant in accordance with EN 12006-2. Justification shall be provided for the property (or
properties) selected to be measured.
7.3 Pre-clinical evaluation: Combination of implant and delivery system (for self-
expanding and balloon-expandable implants)
7.3.1 General
If applicable all tests shall be performed in a model that simulates the vascular anatomy, which
the delivery system is required to negotiate in its clinical application and under the intended and
specified use conditions. Testing shall be performed in an atmosphere of 100 % relative humidity
or water and a temperature of (37 ± 2) °C, if humidity and/or temperature have an influence on
the test results.
7.3.2 Dimension
The manufacturer shall demonstrate and document that all dimensions and the profile of each
component and accessory of the delivery system are compatible with safe access, deployment,
and withdrawal.
7.3.3 Flexibility
T he manufacturer shall demonstrate that the implant has sufficient flexibility to negotiate the
vascular/arterial anatomy for which it is intended without compromising the function of the implant
or causing it to kink. Also determine the minimum radius of curvature that the implant can
accommodate without kinking.
7.3.4 Bond strength and torsional bond strength
7.3.4.1 General
The manufacturer shall determine the forces required to break the joints and the materials of the
delivery system. The results shall be evaluated in relation to the force required to separate the
delivery system from the implant and the force needed to pull back the delivery system in the
guiding catheter. The test method, the results and the evaluation shall be documented.
Balloon catheters shall also comply with Clause 4.5 of EN ISO 10555-1:1996.
7.3.4.2 Torquability
Evaluate the ability of the delivery system to provide sufficient rotation to the distal end to deliver
the implant within the anatomy in accordance with the design constraints of the system.
7.3.4.3 Pushability
Determine the ability of the delivery system to be pushed or positioned by an operator without
bending or buckling.
7.3.4.4 Trackability
7.3.4.4.1 General
Determine the ability of the delivery system to advance over a guidewire, following the guidewire
tip, along the path of the vessel, including in narrow and/or tortuous vessels. The guidewire
characteristics shall be documented. The elements of the simulated anatomy that the delivery
system had difficulty negotiating shall be evaluated and documented.
7.3.4.4.2 Profile effect / flaring (for balloon-expandable implants)
For any premounted balloon-expandable implant, the manufacturer shall evaluate the possible
radial detachment of the implant from its balloon at its proximal and distal ends during the
passage through simulated arterial curvature and the potential for balloon damage during implant
placement. The distance between the external diameter of the implant and the external diameter
of the balloon shall be measured. The greater the distance, the higher the risk of the implant
sticking to the arterial wall when going through the curvature.
If the results of this test are not satisfactory, the manufacturer shall exclude direct stenting with
this implant.
7.3.4.4.3 Dislodgement force (for balloon-expandable implants)
For any premounted balloon-expandable implant, the manufacturer shall determine the force
required to pull off the crimped implant from the non-expanded balloon. Tests shall be conducted
both at the proximal and distal ends of the implant:
1) on a straight delivery system;
2) on a straight delivery system after passage through simulated arterial curvature.
7.3.4.5 Balloon tests
7.3.4.5.1 General
The requirements of EN ISO 10555-1 and EN ISO 10555-4 apply.
The following tests shall be conducted to a complete system, which simulates the in vivo
conditions.
7.3.4.5.2 Balloon inflation
T he minimal time required to expand the balloon to the maximum recommended inflation
pressure shall be quantified.
The following equipment shall be used:
• water bath filled with water of (37 ± 2) °C;
• thermometer;
• inflation device filled with an appropriate liquid used clinically;
• stop-watch;
• appropriate environment adapted to the size of the balloon/stent combination;
• guidewire.
The test shall be performed as follows:
• position the guidewire in the catheter;
• place the catheter in the water bath. At least 80 % of the shaft and the balloon shall be soaked
in the water bath;
• equilibrate for at least 2 min;
• pressurize the catheter with implant to the maximum recommended inflation pressure;
• measure the minimal time required to inflate the balloon to the maximum recommended
inflation pressure;
• deflate the balloon.
7.3.4.5.3 Balloon deflating
The time required to deflate the balloon shall be measured and the ability to remove the deflated
balloon shall be evaluated.
The following equipment shall be used:
• water bath filled with water of (37 ± 2) °C;
• thermometer;
• inflation device filled with an appropriate liquid used clinically;
• stop-watch;
• appropriate environment adapted to the size of the balloon/implant combination;
• guidewire.
The test shall be performed as follows:
• position the guidewire in the catheter;
• condition the catheter in the water bath. At least 80 % of the shaft and the balloon shall be
soaked in the water bath;
• pressurize the catheter with implant to the maximum recommended inflation pressure;
• deflate the balloon;
• measure the time to complete the deflation;
• evaluate the ability to remove the deflated balloon from the implant.
7.3.4.5.4 Maximum recommended inflation pressure (for non-compliant balloons)
The maximum recommended inflation pressure shall be determined.
W hen the balloon bursts it shall be verified that the tear is longitudinal.
The following equipment shall be used:
• water bath to maintain a temperature of (37 ± 2) °C;
• thermometer;
• inflation device filled with fluid;
• appropriate environment adapted to the size of the balloon/implant combination;
• pressure monitoring device;
• guidewire.
T he test shall be performed as follows:
• pressurize the catheter until burst according to normal clinical conditions (progressive
pressure inflation rate);
• determine the mean burst pressure;
• determine the maximum recommended inflation pressure (mean burst pressure with an
appropriate safety margin).
7.3.4.5.5 Balloon rated fatigue
The number of inflation cycles to the maximum recommended inflation pressure shall be
determined (see Clause 4.4.2 and Annex A of EN ISO 10555-4:1997).
T he following equipment shall be used:
• water bath filled to maintain a temperature of (37 ± 2) °C;
• thermometer;
• inflation device filled with water;
• guidewire.
The test shall be performed as follows:
• connect the inflation port of the catheter to the inflation device;
• condition the catheter in the water bath for an appropriate duration and leave the catheter in
the water bath;
• pressurize the catheter to the maximum recommended inflation pressure;
• maintain the pressure for 10 s;
• deflate the balloon;
• repeat the steps, pressurizing, maintaining pressure and deflating the balloon 10 times.
If the balloon bursts or any other failure occurs the number of inflations/deflations and the failure
mode shall be recorded.
7.3.4.5.6 Dogboning
NOTE Direct stenting is an implantation procedure increasingly used by clinicians. It requires the
balloon to be inflated to a high pressure (up to 15 bars) in order to break the atheromatous plaque and at the
same time release the implant. In this case, if the proximal and distal ends of the balloon beyond the implant
tend to inflate to a diameter greater than that of the implant, it may cause injury to the artery.
For any premounted balloon-expandable implant, the manufacturer shall evaluate the difference
between the diameter of the implant and those of the proximal and distal ends of the balloon
when the implant is released under the maximum recommended inflation pressure.
If unacceptable dogboning occurs, the manufacturer shall exclude direct stenting with this
implant.
7.3.5 Hemostasis
The requirements of EN ISO 11070 apply, together with the following. The ability of the entire
system to minimize blood loss shall be considered. This should include, but not be limited to the
following:
a) size mismatch;
b) seal incompetence;
c) other leakage.
7.4 Pre-clinical evaluation: animal testing
7.4.1 General
The requirements of Clause 7.6 of EN 12006-3:1998 apply.
7.4.2 Purpose
The purpose of in vivo pre-clinical testing is to evaluate the deployment of the implant and to
obtain data pertaining to the performance and un-anticipated side effects of the implant in vivo.
The testing shall evaluate the suitability of the implant for its intended use in clinical investigation.
7.4.3 Specific aims
The following items are specific aims of in vivo pre-clinical evaluation:
a) evaluate the ability to access the target location with the delivery system;
b) evaluate the handling and visualization of the delivery system and visualization of the
implant;
c) verify the accuracy and efficacy of deployment;
d) characterize the ability to withdraw the delivery system;
e) evaluate the appropriateness of implant sizing;
f) evaluate the functional haemostasis of the delivery system and sheath introducer;
g) evaluate the position, structural and material integrity, and functionality of the implant acutely
and over time and at explanation;
h) evaluate histology and pathology of explants and pertinent tissues/organs;
i) adverse events.
7.4.4 Protocol
The choice of animal model shall be justified taking account of the intended use of the implant, to
ensure the highest degree of human compatibility conditions.
For coronary stents incorporating new significant characteristics or for any new intended use, a
minimum of 25 stents shall be evaluated, and the majority shall be reviewed after a minimum of
6 months implantation. A shorter-term study may be performed if an acceptable justification is
provided. For endovascular prostheses, a minimum of 6 prostheses shall be reviewed after at
least 6 months implantation. Longer follow-up periods may be required for new materials, which
do not have a history of use in vascular implants.
All implants shall be evaluated for at least 3 implants at a minimum of two interim sacrifice
periods. The timing of the interim assessments shall be determined by the characteristics of the
chosen animal model in order to obtain information on relevant endpoints, which will be of clinical
relevance including; implant thrombogenicity, implant endothelialisation, vessel erosion,
in-implant stenosis or restenosis etc. Marker or implant visibility and migration resistance shall
also be documented.
All animals in the study shall be regularly examined. For ailing animals the cause of illness and
the extent to which the implant was implicated shall be documented. Animals dying during the
study shall be subject to early post mortem examination and the data shall be included within the
final report. Histo-pathological assessment of explants and appropriate tissues and/or organs
shall be provided.
7.4.5 Data acquisition
The following minimum data shall be recorded for each animal receiving an implant:
a) identification data:
1. source of animals;
2. animal identification;
3. gender;
4. date of birth;
5. weight;
b) pre-operative data:
1. verification of health status, including appropriate blood testing;
2. medications (e.g., prophylactic antibiotics);
c) operative data:
1. date of procedure;
2. name of person performing procedure;
3. description of the implant procedure including:
i) implant identification number;
ii) in situ length and diameter of implant;
iii) amount of oversizing;
iv) use of systemic antiplatelet / anticoagulant therapy.
4. assessment of accuracy and efficacy of insertion of delivery system and deployment of
the implant;
5. assessment of handling and visualization of the delivery system and visualization of the
implant;
6. assessment of efficacy of withdrawal of delivery system;
7. assessment of appropriateness of sizing and sizing scheme;
8. amount and location of blood loss;
9. assessment of position, structural and material integrity, and functionality of the implant;
10. adverse peri-operative events.
d) post-operative data:
1. medications, including those that affect coagulation;
2. observation of endoleaks, structural integrity, functionality and position of implant,
method of visualization, and date;
3. adverse events, date of occurrence, therapy, and outcome;
4. any major deviation from protocol.
e) termination data:
1. observation of endoleaks, structural integrity, functionality, patency and position of
implant, method of visualization and date of sacrifice;
2. gross alteration in the dimensional, chemical and physical properties of the implant and
components;
3. histo-pathological assessment of explants and appropriate tissues and/or organs.
7.4.6 Test report and additional information
Results of all animals enrolled in the protocol shall be recorded and reported even if excluded
from the final analysis.
The test report shall include the following:
a) study protocol;
b) rationale for selection of the following:
1. animal species;
2. implantation site;
3. implantation periods;
4. methods of assessment;
5. intervals of observation;
6. sample size (i.e. number of animals and implants).
c) summary of results:
1. animal accountability, including rationale for exclusion of data;
2. success rates relative to the objectives;
3. adverse events;
4. summary of early deaths or sacrifices for cause;
5. operator opinion of ease of deployment, visualization and handling;
6. any deviations from protocol;
7. summary of pathology and histology of explants and appropriate tissues and/or organs,
including representative gross photographs and micrographs and their corresponding
implant durations;
8. summary of any changes in position, structural and material integrity, and function of the
implant;
9. conclusions from study;
10. summary of quality assurance and data auditing procedures.
7.5 Clinical evaluation
7.5.1 General
The requirements of Clause 7.7 of EN 12006-3:1998 apply.
The requirements of EN ISO 14155-1 and EN ISO 14155-2 apply.
7.5.2 Purpose
The purpose of clinical evaluation is to evaluate the performance of the delivery system and
assess the safety and performance of an implant and its delivery system. This evaluation is not
intended to demonstrate the long-term performance of the implant.
An investigation shall be carried out for each new implant or new clinical application of an implant
prior to market approval. Significant design changes that may impact safety and performance
shall require clinical evaluation. Additional implant sizes outside the previously evaluated range
shall require clinical evaluation. The implant shall have satisfied all appropriate preclinical testing
requirements of this standard before starting the clinical investigation.
7.5.3 Specific aims
Specific aims of the study shall be stated and shall include the following, as appropriate (see
Annex A):
a) evaluate the ability to access the target location with the delivery system;
b) evaluate the handling and visualization of the delivery system and visualization of the
implant;
c) verify the accuracy and efficacy of deployment;
d) evaluate the ability to withdraw the delivery system;
e) evaluate the appropriateness of implant sizing;
f) evaluate the functional haemostasis of the delivery system and accessory devices;
g) evaluate the position, structural and material integrity, and functionality of the implant acutely
and over time;
h) monitor lesion characteristics and implant positioning (over time);
i) report the early and late conversions and the cause;
j) evaluate histology and pathology of any explants and tissues and/or organs;
k) record reportable adverse events.
7.5.4 Study design, data acquisition, and final report
A method for evaluating the clinical outcomes shall be prospectively defined and justified.
Consideration shall be given to use of an appropriate control. All patients implanted with either a
test or reference implant/delivery systems, including those excluded from the final analysis, shall
be reported. The final report shall include current follow-up data on all patients with follow-up as
specified by the protocol for the last patient enrolled. Patient follow-up intervals shall include at
least a baseline assessment at discharge from the institution and at the end of the trial.
The actual timing and number of patient follow-up assessments and the method of assessment
shall be chosen so as to acquire optimal data on clinical endpoints relevant to the implant in
question.
The clinical study for implants shall be prospective and multicentre.
A justification for the number of investigational sites shall be provided. A statistical justification for
the number of patients included shall be provided based upon the clinical hypotheses. The
calculation of the number of patients to be enrolled shall take account of the effect of
comorbidities on the life-expectancy of the patient population.
The duration of patient follow-up shall be determined in relation to the objectives of the clinical
investigation.
For endovascular prostheses and carotid stents the clinical investigation duration shall be
12 months for each patient. After completion of the study follow-up is advised for a minimum of
24 months for carotid stents and 48 months for endovascular prostheses.
7.5.5 Protocol
The requirements of EN ISO 14155-1 and EN ISO 14155-2 or an equivalent publication apply.
7.5.6 Data acquisition
At least the following data shall be recorded for each patient in the study.
NOTE Exceptions for the control population are stated below.
a) identification data:
1. patient identification;
2.
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