Cardiovascular implants and artificial organs — Cannulae for extracorporeal circulation

This document specifies requirements for sterile, single-use cannulae for removal and delivery of patients’ blood during cardiopulmonary bypass (CPB) up to 6 h duration, extracorporeal lung assist (ECLA with VV, VAV, or AV cannulation strategies), left or right heart bypass (LHB, RHB), cardiopulmonary support (CPS), extracorporeal life support (ECLS with VA cannulation strategy), extracorporeal carbon dioxide removal (ECCO2R), and other extracorporeal circulation techniques. This standard does not apply to: — introducers (e.g., guidewires) as addressed in ISO 11070, — isolated organ perfusion cannulae, and — intravascular catheters as addressed in ISO 10555-3.

Implants cardiovasculaires et organes artificiels — Canules pour circulation extracorporelle

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Status
Published
Publication Date
12-Aug-2021
Current Stage
6060 - International Standard published
Start Date
13-Aug-2021
Completion Date
13-Aug-2021
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INTERNATIONAL ISO
STANDARD 18193
First edition
2021-08
Cardiovascular implants and artificial
organs — Cannulae for extracorporeal
circulation
Implants cardiovasculaires et organes artificiels — Canules pour
circulation extracorporelle
Reference number
ISO 18193:2021(E)
ISO 2021
---------------------- Page: 1 ----------------------
ISO 18193:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021

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: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
---------------------- Page: 2 ----------------------
ISO 18193:2021(E)
Contents Page

Foreword ..........................................................................................................................................................................................................................................v

Introduction ................................................................................................................................................................................................................................vi

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 2

4 Requirements .......................................................................................................................................................................................................... 4

4.1 Biological characteristics ............................................................................................................................................................... 4

4.1.1 Sterility and non-pyrogenicity ............................................................................................................................. 4

4.1.2 Biocompatibility ............................................................................................................................................................... 4

4.2 Physical characteristics ................................................................................................................................................................... 4

4.2.1 Blood pathway integrity ............................................................................................................................................ 4

4.2.2 Connectors ............................................................................................................................................................................ 4

4.2.3 Kink resistance .................................................................................................................................................................. 5

4.2.4 Pull strength......................................................................................................................................................................... 5

4.2.5 External surface ................................................................................................................................................................ 5

4.2.6 Integrity (corrosion, abrasion, degradation) ........................................................................................... 5

4.2.7 Radio-detectability ......................................................................................................................................................... 5

4.2.8 Distance markings .......................................................................................................................................................... 5

4.2.9 Lumen markings .............................................................................................................................................................. 5

4.3 Performance characteristics........................................................................................................................................................ 5

4.3.1 Pressure drop ..................................................................................................................................................................... 5

4.3.2 Collapse resistance ........................................................................................................................................... .............. 6

4.3.3 Recirculation ....................................................................................................................................................................... 6

4.3.4 Blood cell damage ........................................................................................................................................................... 6

4.3.5 Shelf life ................................................................................................................................................................................... 6

5 Tests and measurements for conformity to this document ..................................................................................... 6

5.1 General ........................................................................................................................................................................................................... 6

5.2 Biological characteristics ............................................................................................................................................................... 7

5.2.1 Sterility and non-pyrogenicity ............................................................................................................................. 7

5.2.2 Biocompatibility ............................................................................................................................................................... 7

5.3 Physical characteristics ................................................................................................................................................................... 7

5.3.1 Blood pathway integrity ............................................................................................................................................ 7

5.3.2 Connectors ............................................................................................................................................................................ 7

5.3.3 Kink resistance .................................................................................................................................................................. 7

5.3.4 Pull strength......................................................................................................................................................................... 8

5.3.5 Integrity (corrosion, abrasion, degradation) ........................................................................................... 8

5.3.6 Radio-detectability ......................................................................................................................................................... 8

5.4 Performance characteristics........................................................................................................................................................ 9

5.4.1 Pressure drop ..................................................................................................................................................................... 9

5.4.2 Collapse resistance ........................................................................................................................................... .............. 9

5.4.3 Recirculation ....................................................................................................................................................................... 9

5.4.4 Blood cell damage ........................................................................................................................................................10

5.4.5 Shelf life ................................................................................................................................................................................11

6 Information supplied by the manufacturer ..........................................................................................................................11

6.1 Information to be given on the cannula ......... .................................................................................................................11

6.2 Information to be given on the packaging ....................................................................................................................12

6.2.1 Unit container ..................................................................................................................................................................12

6.2.2 Shipping container ......................................................................................................................................................12

6.3 Information to be given in the accompanying documents .............................................................................12

6.4 Information to be given in the accompanying documents in a prominent form ........................13

7 Packaging ..................................................................................................................................................................................................................13

© ISO 2021 – All rights reserved iii
---------------------- Page: 3 ----------------------
ISO 18193:2021(E)

Annex A (informative) Examples of connectors .....................................................................................................................................14

Annex B (informative) Test set-up for kink resistance ...................................................................................................................24

Annex C (informative) Test set-up for recirculation ..........................................................................................................................26

Annex D (informative) Test set-up for blood cell damage ...........................................................................................................29

Bibliography .............................................................................................................................................................................................................................33

iv © ISO 2021 – All rights reserved
---------------------- Page: 4 ----------------------
ISO 18193:2021(E)
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards

bodies (ISO member bodies). The work of preparing International Standards is normally carried out

through ISO technical committees. Each member body interested in a subject for which a technical

committee has been established has the right to be represented on that committee. International

organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.

ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of

electrotechnical standardization.

The procedures used to develop this document and those intended for its further maintenance are

described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the

different types of ISO documents should be noted. This document was drafted in accordance with the

editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of

any patent rights identified during the development of the document will be in the Introduction and/or

on the ISO list of patent declarations received (see www .iso .org/ patents).

Any trade name used in this document is information given for the convenience of users and does not

constitute an endorsement.

For an explanation 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 Technical Committee ISO/TC 150, Implants for surgery, Subcommittee

SC 2, Cardiovascular implants and extracorporeal systems.

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.
© ISO 2021 – All rights reserved v
---------------------- Page: 5 ----------------------
ISO 18193:2021(E)
Introduction

This document is intended to ensure that cannulae designed to enable extracorporeal circulation (ECC)

have been adequately tested for both their safety and function, and that cannulae characteristics are

appropriately disclosed when labelling the device.

This document therefore contains procedures to be used for the evaluation of ECC cannulae. Type

test procedures for determination of the cannulae performance and blood cell damage are described,

although limits for these characteristics are not specified. Ready identification of the performance

characteristics should, however, assist the user in the selection of cannulae that suits the needs of the

patient.

This document also includes minimum reporting requirements, which allows the user to compare

performance characteristics of cannulae of different designs in a standard way.

This document makes reference to other international standards in which methods for determination

of characteristics common to medical devices can be found.

Requirements for animal and clinical studies have not been included in this document. Such studies can

be necessary for regulatory submissions and/or be parts of a manufacturer's quality system.

This document contains only those requirements that are specific to cannulae. Non-specific

requirements are covered by references to other International Standards listed in Clause 2. Since non-

toxicity is anticipated to be the subject of a future horizontal/level 1 standard, this document does not

cover non-toxicity.
vi © ISO 2021 – All rights reserved
---------------------- Page: 6 ----------------------
INTERNATIONAL STANDARD ISO 18193:2021(E)
Cardiovascular implants and artificial organs — Cannulae
for extracorporeal circulation
1 Scope

This document specifies requirements for sterile, single-use cannulae for removal and delivery

of patients’ blood during cardiopulmonary bypass (CPB) up to 6 h duration, extracorporeal lung

assist (ECLA with VV, VAV, or AV cannulation strategies), left or right heart bypass (LHB, RHB),

cardiopulmonary support (CPS), extracorporeal life support (ECLS with VA cannulation strategy),

extracorporeal carbon dioxide removal (ECCO R), and other extracorporeal circulation techniques.

This standard does not apply to:
— introducers (e.g., guidewires) as addressed in ISO 11070,
— isolated organ perfusion cannulae, and
— intravascular catheters as addressed in ISO 10555-3.
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 10993-4, Biological evaluation of medical devices — Part 4: Selection of tests for interactions with

blood

ISO 10993-7, Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals

ISO 10993-11, Biological evaluation of medical devices — Part 11: Tests for systemic toxicity

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 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 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 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 80369-7, Small-bore connectors for liquids and gases in healthcare applications — Part 7: Connectors

for intravascular or hypodermic applications
ASTM F640-12, Standard Test Methods For Determining Radiopacity For Medical Use
© ISO 2021 – All rights reserved 1
---------------------- Page: 7 ----------------------
ISO 18193:2021(E)

DIN 13273-7, Catheters for medical use — Part 7: Determination of the x-ray attenuation of catheters;

Requirements and testing
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
extracorporeal circulation

blood circulation through an extracorporeal circuit used to support or replace a subject’s circulatory

and/or gas exchange requirements when the heart and/or lungs are temporarily not capable of

functioning normally (e.g. due to lung and/or heart disease) incorporating cannulae, oxygenators,

tubing, and/or other devices such as blood pump, arterial filter, reservoir
3.2
cannula

tubular device, single-lumen (3.4) or dual-lumen (3.5), designed to be partially inserted into the

cardiovascular system for connection of the patient to the extracorporeal circuit

3.3
blood pathway

portions of the cannula (3.2) in contact with blood during the intended clinical use

3.4
single-lumen

cannula (3.2) with one inner lumen used to draw blood from the patient or to return blood to the patient

3.5
dual-lumen

cannula (3.2) with two inner lumens, separated from each other, used to draw blood from and to return

blood to the patient
3.6
integral part

part that is connected to the cannula (3.2) and that cannot normally be separated by the user

3.7
operating variable
setting of controls that affects the function of the device
3.8
platelet reduction

percentage reduction of platelets contained in a circuit incorporating a cannula (3.2)

3.9
plasma free haemoglobin level

concentration of plasma free haemoglobin in a circuit incorporating a cannula (3.2)

3.9.1
NIH
normalized index of haemolysis
2 © ISO 2021 – All rights reserved
---------------------- Page: 8 ----------------------
ISO 18193:2021(E)
grams of plasma free haemoglobin released after pumping 100 l of blood
100 -Hct
100
Nf()gl/100 =⋅ Δ V ⋅⋅ (1)
ih Hb
100 Qt⋅
where
N is NIH;

Δf is the increase of plasma free haemoglobin concentration (g/l) over the sampling time interval;

V is the circuit volume (l);
Q is the flow rate (l/min);
Hct is the haematocrit (%);
t is the sampling time interval (min).
3.10
white blood cell reduction

percentage reduction of white blood cells contained in a circuit incorporating a cannula (3.2)

3.11
blood analogue

test solution which simulates certain blood characteristics relevant for testing, such as viscosity and

salinity
3.12
predicate cannula

similar cannula (3.2) to the test cannula that is a legally marketed device, recognized-to-be-safe and is

used for the same intended clinical use
3.13
distal end
end of the cannula (3.2) inserted furthest into the patient
3.14
proximal end

end(s) of the cannula (3.2) furthest away from the patient to which connection(s) can be made

3.15
inside diameter

inner diameter of the cannula (3.2), measured at the smallest part of the cannula

Note 1 to entry: The inside diameter is given in millimetres.
3.16
outside diameter

outer diameter of the cannula (3.2), measured at the biggest part of the cannula intended for insertion

Note 1 to entry: The outside diameter is given in millimetres.
3.17
effective length
length of the cannula (3.2), that can be inserted into the body
Note 1 to entry: The effective length is given in millimetres.
3.18
French size
diameter, D , that is three times the normal diameter, D, in millimetres, D = 3D
fr fr
© ISO 2021 – All rights reserved 3
---------------------- Page: 9 ----------------------
ISO 18193:2021(E)
3.19
primary packaging

packaging which has direct contact with the device and/or maintains the sterility of the product

3.20
simulated use

use similar to the intended clinical use in an appropriate in-vitro test circuit with a blood analogue

(3.11) at maximum flow rate as specified by the manufacturer and for the duration specified by the

manufacturer for intended clinical use
3.21
vascular model

tubular structure of diameter two times the outer diameter of the device

under test
3.22
vascular model

simplified vascular model of superior vena cava, right atrium, and inferior vena

cava for testing dual-lumen cannulae intended for use as a single cannula (3.2), for both venous drainage

and return of blood via cannulation of the internal jugular vein
Note 1 to entry: See Annex C.
4 Requirements
4.1 Biological characteristics
4.1.1 Sterility and non-pyrogenicity
The cannula shall be sterile and non-pyrogenic.
Conformity shall be verified in accordance with 5.2.1.
4.1.2 Biocompatibility

All parts of the blood pathway and all tissue contacting parts of the cannula shall be biocompatible with

respect to their intended use.
Conformity shall be verified in accordance with 5.2.2.
4.2 Physical characteristics
4.2.1 Blood pathway integrity
When tested in accordance with 5.3.1, the blood pathway(s) shall not leak.
4.2.2 Connectors

Connectors for connection to the blood pathway shall, when tested in accordance with 5.3.2, allow a

secure connection.

Connectors with dimensions as given in the Annex A and fitting to functional gauges and reference

steel fittings are a way to comply with this requirement. Performance testing of the connectors shall be

performed according to ISO 80369-7:2021, Clause 6, using the reference fittings given in Annex A.

NOTE Connectors of a type that allow connection of tubes with an inner diameter of 4,8 mm, 6,3 mm, 9,5 mm

or 12,7 mm, or a type that complies with ISO 8637-1:2017, Figure 1, or a type that complies with ISO 80369-7:2021

have been found satisfactory.
4 © ISO 2021 – All rights reserved
---------------------- Page: 10 ----------------------
ISO 18193:2021(E)
4.2.3 Kink resistance

When tested in accordance with 5.3.3 the cannula shall not kink. Kinking is defined as a deformation of

lumen of the device when the bending causes a decrease in flow such that the initial flow through the

straight cannula is reduced by more than 50 %.
4.2.4 Pull strength

When tested in accordance with 5.3.4, each cannula shall withstand without disintegration an axial

tensile force of a minimum of 15 N or 1,5 times the force possibly occurring during the intended use as

determined by the risk assessment of the manufacturer for a duration of 30 s.
4.2.5 External surface

When examined by normal or corrected to normal vision, with a minimum ×2 magnification the

external surface of the effective length of the cannula shall appear free from extraneous matter per

manufacturer’s specification.

The external surface of the effective length of the cannula, including the distal end, shall be free from

process and surface defects which could cause trauma to vessels during use or obstruct flow, per

manufacturer’s specification.
4.2.6 Integrity (corrosion, abrasion, degradation)

When examined in accordance with 5.3.5 by normal or corrected to normal vision, with a minimum ×2

magnification the surface of the cannula shall appear free from corrosion, abrasion, and degradation

per manufacturer’s specifications.
4.2.7 Radio-detectability

When examined in accordance with 5.3.6 parts of the cannula shall be radio-detectable, if required as

determined by the risk assessment.
4.2.8 Distance markings

If the cannula is provided with distance markings, the marking system shall indicate distance from the

distal end. From the first mark, the distance between marks should not exceed 50 mm or a distance

determined by risk management.

It is recommended that the distance marks be 10 mm or less apart on that portion of the cannula likely

to be of importance to the user in positioning the cannula and monitoring cannula migration.

4.2.9 Lumen markings

If the cannula is not axially symmetric, the position of any side outlets shall be identifiable by the user on

the proximal end when the cannula is inserted as defined by the information given by the manufacturer.

For dual-lumen cannulae, the direction of blood flow of each lumen shall be visually identifiable by the

user.
4.3 Performance characteristics
4.3.1 Pressure drop

When determined in accordance with 5.4.1, the cannula pressure drop shall be within the range of

values specified by the manufacturer.
© ISO 2021 – All rights reserved 5
---------------------- Page: 11 ----------------------
ISO 18193:2021(E)
4.3.2 Collapse resistance

For drainage cannula, when determined in accordance with 5.4.2, the cannula-induced pressure drop

shall not increase by more than 50 %.
4.3.3 Recirculation

For dual-lumen cannulae, the percentage of recirculated blood in relation to the blood flow through

the extracorporeal circuit shall be within the range of values specified by the manufacturer, when

determined in accordance with 5.4.3.
4.3.4 Blood cell damage
4.3.4.1 Plasma-free haemoglobin

When determined in accordance with 5.4.4, the increased concentration of plasma free haemoglobin

shall be within the range of values specified by the manufacturer.
The haemolysis results shall be reported as mg/dl and NIH.
4.3.4.2 Platelet and white blood cell reduction

When determined in accordance with 5.4.4, the platelet reduction and the white blood cell reduction

shall be within the range of values specified by the manufacturer.
4.3.5 Shelf life

Test results should demonstrate the rated shelf life, as specified by the manufacturer.

5 Tests and measurements for conformity to this document
5.1 General

5.1.1 Tests and measurements shall be performed with final, finished, sterilized devices that are

prepared according to the manufacturer's instructions for intended clinical use.

5.1.2 Operating variables shall be those specified by the manufacturer for intended clinical use, unless

otherwise specified.

5.1.3 Unless otherwise stated, the temperature of test liquids shall be (37 ± 2) °C.

5.1.4 If the relationship between variables is non-linear, sufficient determinations shall be made to

permit valid interpolation between data points.

5.1.5 The test or measurement procedures are to be regarded as reference procedures. Other

procedures can be accepted, provided that the alternative procedure has been shown to be of comparable

precision and reproducibility.

5.1.6 Unless otherwise justified, each test shall be performed using a sufficient number of samples to

support a statistical analysis.
6 © ISO 2021 – All rights reserved
---------------------- Page: 12 ----------------------
ISO 18193:2021(E)
5.2 Biological characteristics
5.2.1 Sterility and non-pyrogenicity

Conformity shall be verified by inspection of the manufacturer's documentation on sterilization and

pyrogen testing, in accordance with ISO 17665-1, ISO 11135, ISO 11137-1, ISO 14937 and ISO 10993-11,

as applicable.
5.2.2 Biocompatibility

Conformity shall be verified by test or by inspection of the manufacturer's documentation on

biocompatibility for the finished device, in accordance with ISO 10993-1, ISO 10993-4, and ISO 10993-7,

as applicable.
5.3 Physical characteristics
5.3.1 Blood pathway integrity
5.3.1.1 Test liquid
The test liquid shall be water, or other appr
...

INTERNATIONAL ISO
STANDARD 18193
First edition
Cardiovascular implants and artificial
organs — Cannulae for extracorporeal
circulation
Implants cardiovasculaires et organes artificiels — Canules pour
circulation extracorporelle
PROOF/ÉPREUVE
Reference number
ISO 18193:2021(E)
ISO 2021
---------------------- Page: 1 ----------------------
ISO 18193:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021

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: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii PROOF/ÉPREUVE © ISO 2021 – All rights reserved
---------------------- Page: 2 ----------------------
ISO 18193:2021(E)
Contents Page

Foreword ..........................................................................................................................................................................................................................................v

Introduction ................................................................................................................................................................................................................................vi

1 Scope ................................................................................................................................................................................................................................. 1

2 Normative references ...................................................................................................................................................................................... 1

3 Terms and definitions ..................................................................................................................................................................................... 2

4 Requirements .......................................................................................................................................................................................................... 4

4.1 Biological characteristics ............................................................................................................................................................... 4

4.1.1 Sterility and non-pyrogenicity ............................................................................................................................. 4

4.1.2 Biocompatibility ............................................................................................................................................................... 4

4.2 Physical characteristics ................................................................................................................................................................... 4

4.2.1 Blood pathway integrity ............................................................................................................................................ 4

4.2.2 Connectors ............................................................................................................................................................................ 4

4.2.3 Kink resistance .................................................................................................................................................................. 5

4.2.4 Pull strength......................................................................................................................................................................... 5

4.2.5 External surface ................................................................................................................................................................ 5

4.2.6 Integrity (corrosion, abrasion, degradation) ........................................................................................... 5

4.2.7 Radio-detectability ......................................................................................................................................................... 5

4.2.8 Distance markings .......................................................................................................................................................... 5

4.2.9 Lumen markings .............................................................................................................................................................. 5

4.3 Performance characteristics........................................................................................................................................................ 5

4.3.1 Pressure drop ..................................................................................................................................................................... 5

4.3.2 Collapse resistance ........................................................................................................................................... .............. 6

4.3.3 Recirculation ....................................................................................................................................................................... 6

4.3.4 Blood cell damage ........................................................................................................................................................... 6

4.3.5 Shelf life ................................................................................................................................................................................... 6

5 Tests and measurements for conformity to this document ..................................................................................... 6

5.1 General ........................................................................................................................................................................................................... 6

5.2 Biological characteristics ............................................................................................................................................................... 7

5.2.1 Sterility and non-pyrogenicity ............................................................................................................................. 7

5.2.2 Biocompatibility ............................................................................................................................................................... 7

5.3 Physical characteristics ................................................................................................................................................................... 7

5.3.1 Blood pathway integrity ............................................................................................................................................ 7

5.3.2 Connectors ............................................................................................................................................................................ 7

5.3.3 Kink resistance .................................................................................................................................................................. 7

5.3.4 Pull strength......................................................................................................................................................................... 8

5.3.5 Integrity (corrosion, abrasion, degradation) ........................................................................................... 8

5.3.6 Radio-detectability ......................................................................................................................................................... 8

5.4 Performance characteristics........................................................................................................................................................ 9

5.4.1 Pressure drop ..................................................................................................................................................................... 9

5.4.2 Collapse resistance ........................................................................................................................................... .............. 9

5.4.3 Recirculation ....................................................................................................................................................................... 9

5.4.4 Blood cell damage ........................................................................................................................................................10

5.4.4.2 Procedure ............................................................................................................................................................................10

5.4.5 Shelf life ................................................................................................................................................................................11

6 Information supplied by the manufacturer ..........................................................................................................................11

6.1 Information to be given on the cannula ......... .................................................................................................................11

6.2 Information to be given on the packaging ....................................................................................................................11

6.2.1 Unit container ..................................................................................................................................................................11

6.2.2 Shipping container ......................................................................................................................................................12

6.3 Information to be given in the accompanying documents .............................................................................12

6.4 Information to be given in the accompanying documents in a prominent form ........................13

7 Packaging ..................................................................................................................................................................................................................13

© ISO 2021 – All rights reserved PROOF/ÉPREUVE iii
---------------------- Page: 3 ----------------------
ISO 18193:2021(E)

Annex A (informative) Examples of connectors .....................................................................................................................................14

Annex B (informative) Test set-up for kink resistance ...................................................................................................................24

Annex C (informative) Test set-up for recirculation ..........................................................................................................................26

Annex D (informative) Test set-up for blood cell damage ...........................................................................................................29

Bibliography .............................................................................................................................................................................................................................33

iv PROOF/ÉPREUVE © ISO 2021 – All rights reserved
---------------------- Page: 4 ----------------------
ISO 18193:2021(E)
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards

bodies (ISO member bodies). The work of preparing International Standards is normally carried out

through ISO technical committees. Each member body interested in a subject for which a technical

committee has been established has the right to be represented on that committee. International

organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.

ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of

electrotechnical standardization.

The procedures used to develop this document and those intended for its further maintenance are

described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the

different types of ISO documents should be noted. This document was drafted in accordance with the

editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).

Attention is drawn to the possibility that some of the elements of this document may be the subject of

patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of

any patent rights identified during the development of the document will be in the Introduction and/or

on the ISO list of patent declarations received (see www .iso .org/ patents).

Any trade name used in this document is information given for the convenience of users and does not

constitute an endorsement.

For an explanation 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 Technical Committee ISO/TC 150, Implants for surgery, Subcommittee

SC 2, Cardiovascular implants and extracorporeal systems.

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.
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ISO 18193:2021(E)
Introduction

This document is intended to ensure that cannulae designed to enable extracorporeal circulation (ECC)

have been adequately tested for both their safety and function, and that cannulae characteristics are

appropriately disclosed when labelling the device.

This document therefore contains procedures to be used for the evaluation of ECC cannulae. Type

test procedures for determination of the cannulae performance and blood cell damage are described,

although limits for these characteristics are not specified. Ready identification of the performance

characteristics should, however, assist the user in the selection of cannulae that suits the needs of the

patient.

This document also includes minimum reporting requirements, which allows the user to compare

performance characteristics of cannulae of different designs in a standard way.

This document makes reference to other international standards in which methods for determination

of characteristics common to medical devices can be found.

Requirements for animal and clinical studies have not been included in this document. Such studies can

be necessary for regulatory submissions and/or be parts of a manufacturer's quality system.

This document contains only those requirements that are specific to cannulae. Non-specific

requirements are covered by references to other International Standards listed in Clause 2. Since non-

toxicity is anticipated to be the subject of a future horizontal/level 1 standard, this document does not

cover non-toxicity.
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INTERNATIONAL STANDARD ISO 18193:2021(E)
Cardiovascular implants and artificial organs — Cannulae
for extracorporeal circulation
1 Scope

This document specifies requirements for sterile, single-use cannulae for removal and delivery

of patients’ blood during cardiopulmonary bypass (CPB) up to 6 h duration, extracorporeal lung

assist (ECLA with VV, VAV, or AV cannulation strategies), left or right heart bypass (LHB, RHB),

cardiopulmonary support (CPS), extracorporeal life support (ECLS with VA cannulation strategy),

extracorporeal carbon dioxide removal (ECCO R), and other extracorporeal circulation techniques.

This standard does not apply to
— introducers (e.g., guidewires) as addressed in ISO 11070,
— isolated organ perfusion cannulae, and
— intravascular catheters as addressed in ISO 10555-3.
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 10993-4, Biological evaluation of medical devices — Part 4: Selection of tests for interactions with

blood

ISO 10993-7, Biological evaluation of medical devices — Part 7: Ethylene oxide sterilization residuals

ISO 10993-11, Biological evaluation of medical devices — Part 11: Tests for systemic toxicity

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 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 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 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
ASTM F640-12, Standard Test Methods For Determining Radiopacity For Medical Use

DIN 13273-7, Catheters for medical use — Part 7: Determination of the x-ray attenuation of catheters;

Requirements and testing
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ISO 18193:2021(E)
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
extracorporeal circulation

blood circulation through an extracorporeal circuit used to support or replace a subject’s circulatory

and/or gas exchange requirements when the heart and/or lungs are temporarily not capable of

functioning normally (e.g. due to lung and/or heart disease) incorporating cannulae, oxygenators,

tubing, and/or other devices such as blood pump, arterial filter, reservoir
3.2
cannula

tubular device, single- or dual-lumen, designed to be partially inserted into the cardiovascular system

for connection of the patient to the extracorporeal circuit
3.3
blood pathway

portions of the cannula (3.2) in contact with blood during the intended clinical use

3.4
single-lumen

cannula (3.2) with one inner lumen used to draw blood from the patient or to return blood to the patient

3.5
dual-lumen

cannula (3.2) with two inner lumens, separated from each other, used to draw blood from and to return

blood to the patient
3.6
integral part

part that is connected to the cannula (3.2) and that cannot normally be separated by the user

3.7
operating variable
setting of controls that affects the function of the device
3.8
platelet reduction

percentage reduction of platelets contained in a circuit incorporating a cannula (3.2)

3.9
plasma free haemoglobin level

concentration of plasma free haemoglobin in a circuit incorporating a cannula (3.2)

3.9.1
NIH
normalized index of hemolysis
grams of plasma free hemoglobin released after pumping 100 l of blood
100 -Hct 100
Nf()gl/100 =⋅ Δ V ⋅⋅ (1)
ih Hb
100 Qt⋅
where
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ISO 18193:2021(E)
N is NIH;

Δf is the increase of plasma free hemoglobin concentration (g/l) over the sampling time inter-

val;
V is the circuit volume (l);
Q is the flow rate (l/min);
Hct is the hematocrit (%);
t is the sampling time interval (min)
3.10
white blood cell reduction

percentage reduction of white blood cells contained in a circuit incorporating a cannula (3.2)

3.11
blood analogue

test solution which simulates certain blood characteristics relevant for testing, such as viscosity and

salinity
3.12
predicate cannula

similar cannula (3.2) to the test cannula that is a legally marketed device, recognized-to-be-safe and is

used for the same intended clinical use
3.13
distal end
end of the cannula (3.2) inserted furthest into the patient
3.14
proximal end

end(s) of the cannula (3.2) furthest away from the patient to which connection(s) can be made

3.15
inside diameter

inner diameter of the cannula (3.2), measured at the smallest part of the cannula

Note 1 to entry: The inside diameter is given in millimetres.
3.16
outside diameter

outer diameter of the cannula (3.2), measured at the biggest part of the cannula intended for insertion

Note 1 to entry: The outside diameter is given in millimetres.
3.17
effective length
length of the cannula (3.2), that can be inserted into the body
Note 1 to entry: The effective length is given in millimetres.
3.18
French size
diameter, D , that is three times the normal diameter, D, in millimetres, D = 3D
fr fr
3.19
primary packaging

packaging which has direct contact with the device and/or maintains the sterility of the product

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ISO 18193:2021(E)
3.20
simulated use

use similar to the intended clinical use in an appropriate in-vitro test circuit with a blood analogue

(3.11) at maximum flow rate as specified by the manufacturer and for the duration specified by the

manufacturer for intended clinical use
3.21
vascular model

tubular structure of diameter two times the outer diameter of the device

under test
3.22
vascular model

simplified vascular model of superior vena cava, right atrium, and inferior vena

cava for testing dual-lumen cannulae intended for use as a single cannula for both venous drainage and

return of blood via cannulation of the internal jugular vein
Note 1 to entry: See Annex C.
4 Requirements
4.1 Biological characteristics
4.1.1 Sterility and non-pyrogenicity
The cannula shall be sterile and non-pyrogenic.
Conformity shall be verified in accordance with 5.2.1.
4.1.2 Biocompatibility

All parts of the blood pathway and all tissue contacting parts of the cannula shall be biocompatible with

respect to their intended use.
Conformity shall be verified in accordance with 5.2.2.
4.2 Physical characteristics
4.2.1 Blood pathway integrity
When tested in accordance with 5.3.1, the blood pathway(s) shall not leak.
4.2.2 Connectors

Connectors for connection to the blood pathway shall, when tested in accordance with 5.3.2, allow a

secure connection.

NOTE 1 Connectors of a type that allow connection of tubes with an inner diameter of 4,8 mm, 6,3 mm, 9,5 mm

or 12,7 mm, or a type that complies with ISO 8637:2017, Figure 1, or a type that complies with ISO 80369-7:2016

have been found satisfactory.

NOTE 2 Connectors with dimensions as given in the Annex A and fitting to functional gauges and reference

steel fittings are a way to comply with this requirement. Performance testing of the connectors shall be

performed according to ISO 80369-7:2016, Clause 6, using the reference fittings given in Annex A.

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ISO 18193:2021(E)
4.2.3 Kink resistance

When tested in accordance with 5.3.3 the cannula shall not kink. Kinking is defined as a deformation of

lumen of the device when the bending causes a decrease in flow such that the initial flow through the

straight cannula is reduced by more than 50 %.
4.2.4 Pull strength

When tested in accordance with 5.3.4, each cannula shall withstand without disintegration an axial

tensile force of a minimum of 15 N or 1,5 times the force possibly occurring during the intended use as

determined by the risk assessment of the manufacturer for a duration of 30 s.
4.2.5 External surface

When examined by normal or corrected to normal vision, with a minimum ×2 magnification the

external surface of the effective length of the cannula shall appear free from extraneous matter per

manufacturer’s specification.

The external surface of the effective length of the cannula, including the distal end, shall be free from

process and surface defects which could cause trauma to vessels during use or obstruct flow, per

manufacturer’s specification.
4.2.6 Integrity (corrosion, abrasion, degradation)

When examined in accordance with 5.3.5 by normal or corrected to normal vision, with a minimum ×2

magnification the surface of the cannula shall appear free from corrosion, abrasion, and degradation

per manufacturer’s specifications.
4.2.7 Radio-detectability

When examined in accordance with 5.3.6 parts of the cannula shall be radio-detectable, if required as

determined by the risk assessment.
4.2.8 Distance markings

If the cannula is provided with distance markings, the marking system shall indicate distance from the

distal end. From the first mark, the distance between marks should not exceed 50 mm or a distance

determined by risk management.

It is recommended that the distance marks be 10 mm or less apart on that portion of the cannula likely

to be of importance to the user in positioning the cannula and monitoring cannula migration.

4.2.9 Lumen markings

If the cannula is not axially symmetric, the position of any side outlets shall be identifiable by the user on

the proximal end when the cannula is inserted as defined by the information given by the manufacturer.

For dual-lumen cannulae, the direction of blood flow of each lumen shall be visually identifiable by the

user.
4.3 Performance characteristics
4.3.1 Pressure drop

When determined in accordance with 5.4.1, the cannula pressure drop shall be within the range of

values specified by the manufacturer.
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ISO 18193:2021(E)
4.3.2 Collapse resistance

For drainage cannula, when determined in accordance with 5.4.2, the cannula-induced pressure drop

shall not increase by more than 50 %.
4.3.3 Recirculation

For dual-lumen cannulae, the percentage of recirculated blood in relation to the blood flow through

the extracorporeal circuit shall be within the range of values specified by the manufacturer, when

determined in accordance with 5.4.3.
4.3.4 Blood cell damage
4.3.4.1 Plasma-free haemoglobin

When determined in accordance with 5.4.4, the increased concentration of plasma free haemoglobin

shall be within the range of values specified by the manufacturer.
The haemolysis results shall be reported as mg/dl and NIH.
4.3.4.2 Platelet and white blood cell reduction

When determined in accordance with 5.4.4, the platelet reduction and the white blood cell reduction

shall be within the range of values specified by the manufacturer.
4.3.5 Shelf life

Test results should demonstrate the rated shelf life, as specified by the manufacturer.

5 Tests and measurements for conformity to this document
5.1 General

5.1.1 Tests and measurements shall be performed with final, finished, sterilized devices that are

prepared according to the manufacturer's instructions for intended clinical use.

5.1.2 Operating variables shall be those specified by the manufacturer for intended clinical use, unless

otherwise specified.

5.1.3 Unless otherwise stated, the temperature of test liquids shall be (37 ± 2) °C.

5.1.4 If the relationship between variables is non-linear, sufficient determinations shall be made to

permit valid interpolation between data points.

5.1.5 The test or measurement procedures are to be regarded as reference procedures. Other

procedures can be accepted, provided that the alternative procedure has been shown to be of comparable

precision and reproducibility.

5.1.6 Unless otherwise justified, each test shall be performed using a sufficient number of samples to

support a statistical analysis.
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ISO 18193:2021(E)
5.2 Biological characteristics
5.2.1 Sterility and non-pyrogenicity

Conformity shall be verified by inspection of the manufacturer's documentation on sterilization and

pyrogen testing, in accordance with ISO 17665-1, ISO 11135, ISO 11137-1, ISO 14937 and ISO 10993 11,

as applicable.
5.2.2 Biocompatibility

Conformity shall be verified by test or by inspection of the manufacturer's documentation on

biocompatibility for the finished device, in accordance with ISO 10993-1, IS
...

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