SIST EN ISO 23500:2015

SLOVENSKI STANDARD
SIST EN ISO 23500:2015
01-december-2015
6PHUQLFH]DSULSUDYRLQYRGHQMHNDNRYRVWLWHNRþLQ]DKHPRGLDOL]RLQSRGREQH
WHUDSLMH,62
Guidance for the preparation and quality management of fluids for haemodialysis and
related therapies (ISO 23500:2014)
Leitfaden für die Vorbereitung und das Qualitätsmanagement von Konzentraten für die
Hämodialyse und verwandte Therapien (ISO 23500:2014)
Directives concernant la préparation et le management de la qualité des fluides
d'hémodialyse et de thérapies annexes (ISO 23500:2014)
Ta slovenski standard je istoveten z: EN ISO 23500:2015
ICS:
11.040.20 Transfuzijska, infuzijska in Transfusion, infusion and
injekcijska oprema injection equipment
SIST EN ISO 23500:2015 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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SIST EN ISO 23500:2015

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SIST EN ISO 23500:2015


EN ISO 23500
EUROPEAN STANDARD

NORME EUROPÉENNE

October 2015
EUROPÄISCHE NORM
ICS 11.040.40
English Version

Guidance for the preparation and quality management of
fluids for haemodialysis and related therapies (ISO
23500:2014)
Directives concernant la préparation et le management Leitfaden für die Vorbereitung und das
de la qualité des fluides d'hémodialyse et de thérapies Qualitätsmanagement von Konzentraten für die
annexes (ISO 23500:2014) Hämodialyse und verwandte Therapien (ISO
23500:2014)
This European Standard was approved by CEN on 27 September 2015.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.





EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 23500:2015 E
worldwide for CEN national Members.

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SIST EN ISO 23500:2015
EN ISO 23500:2015 (E)
Contents Page
European foreword . 3

2

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SIST EN ISO 23500:2015
EN ISO 23500:2015 (E)
European foreword
The text of ISO 23500:2014 has been prepared by Technical Committee ISO/TC 150 “Implants for
surgery” of the International Organization for Standardization (ISO) and has been taken over as EN ISO
23500:2015 by Technical Committee CEN/TC 205 “Non-active medical devices” the secretariat of which
is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by April 2016, and conflicting national standards shall be
withdrawn at the latest by April 2016.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 23500:2014 has been approved by CEN as EN ISO 23500:2015 without any modification.
3

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SIST EN ISO 23500:2015

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SIST EN ISO 23500:2015
INTERNATIONAL ISO
STANDARD 23500
Second edition
2014-04-01
Guidance for the preparation and
quality management of fluids for
haemodialysis and related therapies
Directives concernant la préparation et le management de la qualité
des fluides d’hémodialyse et de thérapies annexes
Reference number
ISO 23500:2014(E)
©
ISO 2014

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SIST EN ISO 23500:2015
ISO 23500:2014(E)

COPYRIGHT PROTECTED DOCUMENT
© ISO 2014
All rights reserved. Unless otherwise specified, 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
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2014 – All rights reserved

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SIST EN ISO 23500:2015
ISO 23500:2014(E)

Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
1.1 General . 1
1.2 Inclusions . 1
1.3 Exclusions . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Summary of quality requirements of ISO 13958, ISO 13959 and ISO 11663 .9
4.1 Dialysis water . 9
4.2 Requirements for concentrate .11
4.3 Requirements for dialysis fluid .11
4.4 Record retention .12
5 Critical aspects of system design .12
5.1 Technical aspects .13
5.2 Microbiological aspects .13
6 Validation of system performance .14
6.1 Validation plan .14
6.2 Installation and operational qualification .15
6.3 Performance qualification .16
6.4 Routine monitoring and revalidation .16
7 Quality management .17
7.1 General .17
7.2 Monitoring of fluid quality .17
7.3 Monitoring of water treatment equipment .18
7.4 Monitoring of dialysis water storage and distribution .21
7.5 Monitoring of concentrate preparation .23
7.6 Monitoring of concentrate distribution .23
7.7 Monitoring of dialysis fluid proportioning .23
8 Strategies for microbiological control .24
8.1 General .24
8.2 Disinfection .24
8.3 Microbiological monitoring methods .26
9 Environment .28
10 Personnel .29
Annex A (informative) Rationale for the development and provisions of this
International Standard .30
Annex B (informative) Equipment .34
Annex C (informative) Monitoring guidelines for water treatment equipment,
distribution systems, and dialysis fluid .52
Annex D (informative) Strategies for microbiological control .57
Annex E (informative) Validation .62
Annex F (informative) Special considerations for home haemodialysis .65
Annex G (informative) Special considerations for acute haemodialysis .71
Bibliography .76
© ISO 2014 – All rights reserved iii

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SIST EN ISO 23500:2015
ISO 23500:2014(E)

Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical Barriers
to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This second edition cancels and replaces the first edition (ISO 23500:2011), which has been technically
revised.
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SIST EN ISO 23500:2015
ISO 23500:2014(E)

Introduction
This International Standard was developed by ISO/TC 150/SC 2. The objective was to provide users with
guidance for handling water and concentrates and for the production and monitoring of dialysis fluid
used for haemodialysis. The need for such guidance is based on the critical role of dialysis fluid quality
in providing safe and effective haemodialysis, and the recognition that day-to-day dialysis fluid quality
is under the control of the healthcare professionals who deliver dialysis therapy.
Quality requirements for the water and concentrates used to prepare dialysis fluid, and for that dialysis
fluid, are provided in ISO 13959, ISO 13958, and ISO 11663, respectively. This International Standard
does not address clinical issues that might be associated with inappropriate usage of the water, dialysis
water, concentrates, or dialysis fluid. Healthcare professionals involved in the provision of treatment
for kidney failure should make the final decision regarding the applications with which these fluids are
used, for example, haemodialysis, haemodiafiltration, high-flux haemodialysis, and the reprocessing of
dialysers, and need to be aware of the issues that the use of inappropriate fluid quality raises in each of
the therapies.
The equipment used in the various stages of dialysis fluid preparation is generally obtained from
specialized vendors. Dialysis practitioners are generally responsible for maintaining that equipment
following its installation. Therefore, this International Standard provides guidance on monitoring
and maintenance of the equipment to ensure that dialysis fluid quality is acceptable at all times. At
various places throughout this International Standard, the user is advised to follow the manufacturer’s
instructions regarding the operation and maintenance of equipment. In those instances in which the
equipment is not obtained from a specialized vendor, it is the responsibility of the user to validate the
performance of the equipment in the haemodialysis setting and to ensure that appropriate operating and
maintenance manuals are available. Annex B provides a general description of the system components
that are used for water treatment, concentrate, and dialysis fluid preparation at a dialysis facility. These
descriptions are intended to provide the user with a basis for understanding why certain equipment
might be required and how it should be configured; they are not intended as detailed design standards.
Requirements for water treatment equipment are provided in ISO 26722.
The verbal forms used in this International Standard conform to usage described in Annex H of the
ISO/IEC Directives, Part 2:2004. For the purposes of this International standard, the auxiliary verb:
— “shall” means that compliance with a requirement or a test is mandatory for compliance with this
International Standard;
— “should” means that compliance with a requirement or a test is recommended but is not mandatory
for compliance with this International Standard;
— “may” is used to describe a permissible way to achieve compliance with a requirement or test.
This International Standard reflects the conscientious efforts of healthcare professionals, patients,
and medical device manufacturers to develop recommendations for handling water and concentrates
and for the production and monitoring of dialysis fluid for haemodialysis. This International Standard
is directed towards the healthcare professionals involved in the management or routine care of
haemodialysis patients and responsible for the quality of dialysis fluid. The recommendations contained
in this International Standard might not be applicable in all circumstances and they are not intended for
regulatory application.
The guidance provided by this International Standard should help protect haemodialysis patients
from adverse effects arising from known chemical and microbial contaminants that might be found
in improperly prepared dialysis fluid. However, the physician in charge of dialysis has the ultimate
responsibility for ensuring that the dialysis fluid is correctly formulated and meets the requirements of
all applicable quality standards.
The concepts incorporated in this International Standard should not be considered inflexible or static.
The recommendations presented here should be reviewed periodically in order to assimilate increased
understanding of the role of dialysis fluid purity in patient outcomes and technological developments.
© ISO 2014 – All rights reserved v

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SIST EN ISO 23500:2015

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SIST EN ISO 23500:2015
INTERNATIONAL STANDARD ISO 23500:2014(E)
Guidance for the preparation and quality management of
fluids for haemodialysis and related therapies
1 Scope
1.1 General
This International Standard provides dialysis practitioners with guidance on the preparation of
dialysis fluid for haemodialysis and related therapies and substitution fluid for use in online therapies,
such as haemodiafiltration and haemofiltration. As such, this International Standard functions as a
recommended practice.
1.2 Inclusions
This International Standard addresses the user’s responsibility for the dialysis fluid once the equipment
used in its preparation has been delivered and installed. For the purposes of this International Standard,
the dialysis fluid includes dialysis water (see 3.18 for definition) used for the preparation of dialysis
fluid and substitution fluid, dialysis water used for the preparation of concentrates at the user’s facility,
as well as concentrates and the final dialysis fluid and substitution fluid.
The scope of this International Standard includes
a) the quality management of equipment used to treat and distribute water used for the preparation
of dialysis fluid and substitution fluid, from the point at which municipal water enters the dialysis
facility to the point at which the final dialysis fluid enters the dialyser or the point at which
substitution fluid is infused,
b) equipment used to prepare concentrate from powder or other highly concentrated media at a
dialysis facility, and
c) preparation of the final dialysis fluid or substitution fluid from dialysis water and concentrates.
NOTE Because water used to prepare dialysis fluid is commonly prepared and distributed using the same
equipment as the water used to reprocess dialysers, water used to reprocess dialysers is also covered by this
International Standard.
1.3 Exclusions
This International Standard does not apply to sorbent-based dialysis fluid regeneration systems that
regenerate and recirculate small volumes of dialysis fluid, systems for continuous renal replacement
therapy that use prepackaged solutions, and systems and solutions for peritoneal dialysis.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 11663:2014, Quality of dialysis fluid for haemodialysis and related therapies
ISO 13958:2014, Concentrates for haemodialysis and related therapies
ISO 13959:2014, Water for haemodialysis and related therapies
© ISO 2014 – All rights reserved 1

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SIST EN ISO 23500:2015
ISO 23500:2014(E)

ISO 26722:2014, Water treatment equipment for haemodialysis applications and related therapies
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
acetate concentrate
concentrated solution of salts containing acetate, which, when diluted with dialysis water, yields
bicarbonate-free dialysis fluid for use in dialysis
Note 1 to entry: Acetate concentrate may contain glucose.
Note 2 to entry: Sodium acetate is used to provide buffer in place of sodium bicarbonate.
Note 3 to entry: Acetate concentrate is used as a single concentrate.
3.2
acid concentrate
A-concentrate
acidified concentrated mixture of salts that, when diluted with dialysis water and bicarbonate
concentrate, yields dialysis fluid for use in dialysis
Note 1 to entry: The term “acid” refers to the small amount of acid (for example, acetic acid or citric acid) that is
included in the concentrate.
Note 2 to entry: Acid concentrate may contain glucose.
Note 3 to entry: Acid concentrate may be in the form of a liquid, a dry powder, other highly concentrated media,
or some combination of these forms.
3.3
action level
concentration of a contaminant at which steps should be taken to interrupt the trend toward higher,
unacceptable levels
3.4
additive
spike
small amount of a single chemical that, when added to the concentrate, will increase the concentration
of a single existing chemical by a value labelled on the additive packaging
3.5
bicarbonate concentrate
B-concentrate
concentrated preparation of sodium bicarbonate that, when diluted with dialysis water and acid
concentrate, makes dialysis fluid used for dialysis
Note 1 to entry: Sodium bicarbonate is also known as sodium hydrogen carbonate.
Note 2 to entry: Some bicarbonate concentrates also contain sodium chloride.
Note 3 to entry: Bicarbonate concentrate may be in the form of a liquid or a dry powder.
Note 4 to entry: Dry sodium bicarbonate, without added sodium chloride, is also used in concentrate generators
to produce a concentrated solution of sodium bicarbonate used by the dialysis machine to make dialysis fluid.
2 © ISO 2014 – All rights reserved

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SIST EN ISO 23500:2015
ISO 23500:2014(E)

3.6
biofilm
microbially-derived sessile community characterized by cells that are irreversibly attached to a
substratum or interface or to each other, are imbedded in a matrix of extracellular polymeric substances
that they have produced, and exhibit an altered phenotype with respect to growth rate and gene
transcription
Note 1 to entry: The matrix, a slimy material secreted by the cells, protects the bacteria from antibiotics and
chemical disinfectants.
Note 2 to entry: A certain amount of biofilm formation is considered unavoidable in dialysis water systems. When
the level of biofilm is such that the action levels for microorganisms and endotoxins in the dialysis water cannot
be routinely achieved, the operation of the system is compromised from a medical and technical point of view.
This level of biofilm formation is often referred to as biofouling.
3.7
bulk delivery
delivery of large containers of concentrate to a dialysis facility
Note 1 to entry: Bulk delivery includes containers such as drums, which can be pumped into a storage tank
maintained at the user’s facility. Alternatively, the drums can be left at the facility and used to fill transfer
containers to transfer the concentrate to the dialysis machines. Bulk delivery can also include large containers
for direct connection to a central concentrate supply system.
Note 2 to entry: Bulk delivery also includes dry powder concentrates intended to be used with an appropriate
concentrate mixer.
3.8
central concentrate system
system that prepares and/or stores concentrate at a central point for subsequent distribution to its
points of use
3.9
central dialysis fluid delivery system
system that produces dialysis fluid from dialysis water and concentrate or powder at a central point and
distributes the dialysis fluid from the central point to individual dialysis machines
3.10
chlorine, combined
chlorine that is chemically combined, such as in chloramine compounds
Note 1 to entry: There is no direct test for measuring combined chlorine, but it can be measured indirectly by
measuring both total and free chlorine and calculating the difference.
3.11
chlorine, free
chlorine present in water as dissolved molecular chlorine (Cl), hypochlorous acid (HOCl), and
−
hypochlorite ion (OCl )
Note 1 to entry: The three forms of free chlorine exist in equilibrium.
3.12
chlorine, total
sum of free and combined chlorine
Note 1 to entry: Chlorine can exist in water as dissolved molecular chlorine, hypochlorous acid, and/or hypochlorite
ion (free chlorine) or in chemically combined forms (combined chlorine). Where chloramine is used to disinfect
water supplies, chloramine is usually the principal component of combined chlorine.
© ISO 2014 – All rights reserved 3

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SIST EN ISO 23500:2015
ISO 23500:2014(E)

3.13
colony-forming unit
CFU
measure of bacterial or fungal cell numbers that theoretically arise from a single cell when grown on
solid media
Note 1 to entry: Colonies can also form from groups of organisms when they occur in aggregates.
3.14
concentrate generator
system where the
...