EN ISO 23500:2015

SLOVENSKI STANDARD
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
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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.

Contents Page
European foreword . 3

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.
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
ISO 23500:2014(E)
© 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

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 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.
iv © ISO 2014 – All rights reserved

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.
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 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

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 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 concentrate is delivered to the user as a powder in a container, suitable for attachment
to the dialysis machine with which it is intended to be used, and then the powder is converted into a
concentrated solution by the dialysis machine
Note 1 to entry: The solution produced by the concentrate generator is used by the dialysis machine to make the
final dialysis fluid delivered to the dialyser.
3.15
device
individual dialysis water purification unit, such as a softener, carbon bed, reverse osmosis unit, or
deionizer
Note 1 to entry: This term is synonymous with the term “component” as used by the US Food and Drug
[169]
Administration (see Reference ).
3.16
dialysis fluid
dialysate
dialysis solution
aqueous fluid containing electrolytes and, usually, buffer and glucose, which is intended to exchange
solutes with blood during haemodialysis
Note 1 to entry: The term “dialysis fluid” is used throughout this International Standard to mean the fluid made
from dialysis water and concentrates that is delivered to the dialyser by the dialysis fluid delivery system. Such
phrases as “dialysate” or “dialysis solution” are used in place of dialysis fluid in some countries; however, that
usage is discouraged to avoid confusion.
Note 2 to entry: The dialysis fluid entering the dialyser is referred to as “fresh dialysis fluid”, while the fluid
leaving the dialyser is referred to as “spent dialysis fluid”.
Note 3 to entry: Dialysis fluid does not include prepackaged parenteral fluids used in some renal replacement
therapies, such as haemodiafiltration and haemofiltration.
3.17
dialysis fluid delivery system
device that prepares dialysis fluid online from dialysis water and concentrates or that stores and
distributes premixed dialysis fluid; circulates the dialysis fluid through the dialyser; monitors the
dialysis fluid for temperature, conductivity (or equivalent), pressure, flow, and blood leaks; and, prevents
dialysis during disinfection or cleaning modes
Note 1 to entry: The term includes reservoirs, conduits, proportioning devices for the dialysis fluid, and monitors
and associated alarms and controls assembled as a system for the purposes listed above.
Note 2 to entry: The dialysis fluid delivery system may be an integral part of the single-patient dialysis machine
or a centralized preparation system which feeds multiple bedside monitoring systems.
Note 3 to entry: Dialysis fluid delivery systems are also known as proportioning systems and dialysis fluid supply
systems.
4 © ISO 2014 – All rights reserved

ISO 23500:2014(E)
3.18
dialysis water
water that has been treated to meet the requirements of ISO 13959 and which is suitable for use in
haemodialysis applications, including the preparation of dialysis fluid, reprocessing of dialysers,
preparation of concentrates and preparation of substitution fluid for online convective therapies
3.19
disinfection
destruction of pathogenic and other kinds of microorganisms by thermal or chemical means
Note 1 to entry: Disinfection is a less lethal process than sterilization because it destroys most recognized
pathogenic microorganisms but does not necessarily destroy all microbial forms.
3.20
empty-bed contact time
EBCT
time taken by a fluid to pass through an empty volume equal to the volume of a particle bed
Note 1 to entry: EBCT (min) is calculated from the following formula:
EBCT = V/Q
where
V is the volume of the particle bed, in cubic metres (m );
Q is the flow rate of water through the bed, in cubic metres per minute (m /min).
Note 2 to entry: EBCT is used as an indirect measure of how much contact occurs between particles, such as
activated carbon, and water as the water flows through a bed of particles.
3.21
endotoxin
major component of the outer cell wall of gram-negative bacteria
Note 1 to entry: Endotoxins are lipopolysaccharides, which consist of a polysaccharide chain covalently bound
to lipid A. Endotoxins can acutely activate both humoral and cellular host defences, leading to a syndrome
characterized by fever, shaking, chills, hypotension, multiple organ failure, and even death if allowed to enter the
circulation in a sufficient dose. [See also pyrogen (3.36)].
3.22
endotoxin-retentive filter
ETRF
membrane filter used to remove endotoxins and microorganisms from dialysis water or dialysis fluid
Note 1 to entry: The performance of an endotoxin-retentive filter is usually expressed as the logarithmic reduction
value (LRV), defined as log (inlet concentration)/(outlet concentration).
Note 2 to entry: Endotoxin-retentive filters may be configured in a cross-flow or dead-end mode. Some endotoxin-
retentive filters also remove endotoxins by adsorption.
3.23
endotoxin units
EU
units assayed by the Limulus amoebocyte lysate (LAL) test when testing for endotoxins
Note 1 to entry: Because activity of endotoxins depends on the bacteria from which they are derived, their activity
is referred to a standard endotoxin.
Note 2 to entry: In some countries, endotoxin concentrations are expressed in international units (IU). Since the
harmonization of endotoxin assays, EU and IU are equivalent.
ISO 23500:2014(E)
3.24
feed water
water supplied to a water treatment system or to an individual component of a water treatment system
3.25
germicide
agent that kills microorganisms
3.26
haemodiafiltration
form of renal replacement therapy in which waste solutes are removed from blood by a combination of
diffusion and convection through a high-flux membrane
Note 1 to entry: Diffusive solute removal is achieved using a dialysis fluid stream as in haemodialysis. Convective
solute removal is achieved by adding ultrafiltration in excess of that needed to obtain the desired weight loss; fluid
balance is maintained by infusing a replacement solution into the blood either before the dialyser (predilution
haemodiafiltration), after the dialyser (postdilution haemodiafiltration), or a combination of the two (mixed
dilution haemodiafiltration).
3.27
haemodialysis
form of renal replacement therapy in which waste solutes are removed primarily by diffusion from
blood flowing on one side of a membrane into dialysis fluid flowing on the other side
Note 1 to entry: Fluid removal that is sufficient to obtain the desired weight loss is achieved by establishing a
hydrostatic pressure gradient across the membrane. This fluid removal provides some additional waste solute
removal, particularly for solutes with higher molecular weight.
3.28
haemofiltration
form of renal replacement therapy in which waste solutes are removed from blood by convection
Note 1 to entry: Convective transport is achieved by ultrafiltration through a high-flux membrane. Fluid balance
is maintained by infusing a replacement solution into the blood either before the haemofilter (predilution
haemofiltration), after the haemofilter (postdilution haemofiltration), or a combination of the two (mixed dilution
haemofiltration).
Note 2 to entry: There is no dialysis fluid stream in haemofiltration.
3.29
heterotrophic
not self-sustaining, i.e. a type of nutrition in which organisms derive energy from the oxidation of organic
compounds by either consumption or absorption of other organisms
3.30
Limulus amoebocyte lysate test
LAL test
assay used to detect endotoxin
Note 1 to entry: The detection method uses the chemical response of an extract from blood cells of a horseshoe
crab (Limulus polyphemus) to endotoxins.
Note 2 to entry: Amebocyte lysate from a second horseshoe crab, Tachypleus tridentatus, may also be used to
detect endotoxin.
6 © ISO 2014 – All rights reserved

ISO 23500:2014(E)
3.31
manufacturer
entity that designs, manufactures, fabricates, assembles, or processes a finished device
Note 1 to entry: Manufacturers include, but are not limited to, those who perform the functions of contract
sterilization, installation, relabelling, remanufacturing, repacking, or specification development, and initial
distributions of foreign entities performing these functions. The term does not cover preparation of concentrates
from prepackaged dry chemicals at a dialysis facility or the handling of bulk concentrates at a dialysis facility
after responsibility for the concentrate is transferred from the manufacturer to the user.
3.32
microbiological contamination
contamination with any form of microorganism (e.g. bacteria, yeast, fungi, and algae) or with the by-
products of living or dead organisms, such as endotoxins, exotoxins, and cyanobacterial toxins (derived
from blue-green algae)
3.33
nonpyrogenic
not eliciting a pyrogen reaction
Note 1 to entry: Historically, the threshold pyrogenic dose of 5 EU/kg/h (the minimum dose that produces fever)
has been used to set endotoxin limits of devices and injectable medications.
Note 2 to entry: The volume of fluid administered should not exceed the volume that would result in a total dose
of endotoxin of ≥5 EU/kg/h.
Note 3 to entry: This definition is applicable for fluids produced by online techniques, e.g. substitution and
priming fluids.
Note 4 to entry: The commonly used gel clot method has a sensitivity limit of 0,03 EU/ml.
3.34
product water
water produced by a water treatment system or by an individual device thereof
3.35
proportioning system
apparatus that proportions dialysis water and haemodialysis concentrate to prepare dialysis fluid
3.36
pyrogen
fever-producing substance
Note 1 to entry: Pyrogens are most often lipopolysaccharides of gram-negative bacterial origin [see also endotoxin
(3.21)].
3.37
sodium hypochorite
chemical used for disinfection of haemodialysis systems
Note 1 to entry: Commercially available solutions of sodium hypochlorite are known in different countries by
terms such as bleach and javel. These solutions are used for disinfection at concentrations recommended by
equipment manufacturers.
3.38
source water
water entering a dialysis facility from an external supplier, such as a municipal water supply
Note 1 to entry: Source water is sometimes referred to as feed water.
ISO 23500:2014(E)
3.39
sterile
free from viable microorganisms
Note 1 to entry: “Sterile” can be used to describe a packaged solution that was prepared using a terminal
sterilization process validated according to the methods of the applicable pharmacopoeia. A terminal sterilization
−6
process is commonly defined as one that achieves a sterility assurance level (SAL) of 10 , i.e. assurance of less
than one chance in a million that viable microorganisms are present in the sterilized article.
Note 2 to entry: Alternatively, “sterile” can be used to describe a solution prepared for immediate use by a
continuous process, such as filtration, that has been validated according to the methods of the applicable
pharmacopoeia to produce a solution free from microorganisms for the validated life of the filter.
3.40
storage tank
tank at the user’s facility for storage of dialysis water or concentrate from bulk deliveries, or for
concentrate prepared in bulk at the user’s facility from powder and dialysis water
3.41
substitution fluid
fluid used in haemofiltration and haemodiafiltration treatments which is infused directly into the
patient’s blood as a replacement for the fluid that is removed from the blood by filtration
Note 1 to entry: Substitution fluid is also referred to as substitution solution or replacement solution.
Note 2 to entry: Substitution fluid can also be used for bolus administration, for priming of an extracorporeal
blood circuit, and for returning blood to the patient at the end of a treatment.
3.42
total dissolved solids
TDS
sum of all ions in a solution, often approximated by means of electrical conductivity or resistivity
measurements
Note 1 to entry: TDS measurements are commonly used to assess the performance of reverse osmosis units. TDS
values are often expressed in terms of CaCO , NaCl, KCl, or 442 equivalents, in milligrams per litre (mg/l). [442 is a
solution of sodium sulfate (40 %), sodium bicarbonate (40 %), and sodium chloride (20 %) that closely represents
the conductivity to concentration relationship, on average, for naturally occurring fresh water.]
3.43
ultrapure dialysis fluid
highly purified dialysis fluid that can be used in place of conventional dialysis fluid
Note 1 to entry: A widely accepted specification of ultrapure dialysis fluid is <0,1 CFU/ml and <0,03 EU/ml.
3.44
user
physician or physician’s representative or healthcare professional with a responsibility for the
prescription, production, and delivery of dialysis fluid
3.45
validation
process of documenting that the dialysis water treatment and dialysis fluid production systems, when
installed and operated according to the manufacturer’s recommendations, consistently produce dialysis
water or dialysis fluid meeting the stipulated quality levels
Note 1 to entry: In this context, validation also includes demonstrating that the system is “fit for purpose”.
Note 2 to entry: The term “verification” is also used and refers to demonstrating that the system complies with
applicable regulations, specifications, or other conditions. A dialysis facility might be interested in both validation
and verification of its fluid production systems.
8 © ISO 2014 – All rights reserved

ISO 23500:2014(E)
3.46
water treatment system
collection of water treatment devices and associated piping, pumps, valves, gauges, etc., that together
produce water for dialysis meeting the requirements of ISO 13959 for haemodialysis applications and
deliver it to the point of use
4 Summary of quality requirements of ISO 13958, ISO 13959 and ISO 11663
The quality requirements set forth in this clause are reproduced from the 2014 editions of ISO 13958,
ISO 13959, and ISO 11663. The latest editions of these International Standards should be consulted
to ascertain if there have been any changes to those requirements before implementing the
recommendations of this International Standard.
4.1 Dialysis water
4.1.1 General
The requirements contained in this clause apply to dialysis water at its point of use. As such, these
requirements apply to the water treatment system as a whole and not to each of the devices that make
up the system. However, collectively, the individual devices shall produce water that, at a minimum,
meets the requirements of this clause.
4.1.2 Chemical contaminants in dialysis water
Dialysis water shall not contain substances at levels greater than those listed in ISO 13959 (see T
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