SIST EN ISO 23500-5:2019
(Main)Preparation and quality management of fluids for haemodialysis and related therapies - Part 5: Quality of dialysis fluid for haemodialysis and related therapies (ISO 23500-5:2019)
Preparation and quality management of fluids for haemodialysis and related therapies - Part 5: Quality of dialysis fluid for haemodialysis and related therapies (ISO 23500-5:2019)
This document specifies minimum quality requirements for dialysis fluids used in haemodialysis and
related therapies.
This document includes dialysis fluids used for haemodialysis and haemodiafiltration, including
substitution fluid for haemodiafiltration and haemofiltration.
This document excludes the water and concentrates used to prepare dialysis fluid or the equipment
used in its preparation. Those areas are covered by other International Standards.
Sorbent-based dialysis fluid regeneration systems that regenerate and recirculate small volumes of
dialysis fluid, systems for continuous renal replacement therapy that use pre-packaged solutions, and
systems and solutions for peritoneal dialysis are excluded from this document.
Vorbereitung und Qualitätsmanagement von Konzentraten für die Hämodialyse und verwandte Therapien - Teil 5: Qualität von Flüssigkeiten für die Hämodialyse und verwandte Therapien (ISO 23500-5:2019)
Dieses Dokument legt Mindestanforderungen an die Qualität von Dialysierflüssigkeiten fest, die bei der Hämodialyse und verwandten Therapien zum Einsatz kommen.
Dieses Dokument umfasst Dialysierflüssigkeiten, die für die Hämodialyse und die Hämodiafiltration eingesetzt werden, einschließlich der Substitutionsflüssigkeit für die Hämodiafiltration und die Hämofiltration.
Dieses Dokument behandelt nicht die Anforderungen an das Wasser und die Konzentrate sowie die Ausrüstung zur Herstellung der Dialysierflüssigkeit. Diese Aspekte werden durch weitere Internationale Normen abgedeckt.
Sorbent basierte Dialysierflüssigkeits-Wiederaufbereitungssysteme, in denen kleine Volumina der Dialysierflüssigkeit wiederaufbereitet und wieder in Umlauf gebracht werden, Systeme für die kontinuierliche Nierenersatztherapie, bei denen vorverpackte Lösungen zum Einsatz kommen, sowie Systeme und Lösungen für die Peritonealdialyse sind vom Anwendungsbereich dieses Dokuments ausgenommen.
Préparation et management de la qualité des liquides d'hémodialyse et de thérapies annexes - Partie 5: Qualité des liquides de dialyse pour hémodialyse et thérapies apparentées (ISO 23500-5:2019)
Le présent document spécifie des exigences de qualité minimales pour les liquides de dialyse dans le cadre d'hémodialyses et de thérapies apparentées.
Le présent document inclut les liquides de dialyse utilisés pour l'hémodialyse et l'hémofiltration, y compris le liquide de substitution pour hémodiafiltration et hémofiltration.
Le présent document exclut l'eau et les concentrés utilisés pour préparer le liquide de dialyse ou l'équipement utilisé lors de sa préparation. Ces domaines sont traités par d'autres Normes internationales.
Les systèmes de régénération des liquides de dialyse à base de sorbant qui régénèrent et remettent en circulation de petits volumes de liquide de dialyse, les systèmes d'épuration extra-rénale continue qui utilisent des solutions prêtes à l'emploi et les systèmes et solutions utilisés en dialyse péritonéale sont exclus du présent document.
Priprava in vodenje kakovosti tekočin za hemodializo in podobne terapije - 5. del: Kakovost tekočin za hemodializo in podobne terapije (ISO 23500-5:2019)
Ta dokument določa minimalne zahteve glede kakovosti za tekočine za hemodializo in podobne terapije.
Ta dokument vključuje tekočine za hemodializo in hemodiafiltracijo, vključno z nadomestno tekočino za hemodiafiltracijo in hemofiltracijo.
Ta dokument ne zajema vode in koncentratov, ki se uporabljajo za pripravo dializne tekočine, ali opreme,
ki se uporablja za njeno pripravo. Te vidike obravnavajo drugi mednarodni standardi.
Sistemi za regeneracijo dializne tekočine na osnovi sorbenta za regeneracijo in recirkulacijo majhnih količin
dializne tekočine, sistemi za neprekinjeno nadomestno ledvično zdravljenje, pri katerih se uporabljajo vnaprej pakirane raztopine, ter sistemi in raztopine za peritonealno dializo so izključeni iz tega dokumenta.
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 23500-5:2019
01-maj-2019
1DGRPHãþD
SIST EN ISO 11663:2016
3ULSUDYDLQYRGHQMHNDNRYRVWLWHNRþLQ]DKHPRGLDOL]RLQSRGREQHWHUDSLMHGHO
.DNRYRVWWHNRþLQ]DKHPRGLDOL]RLQSRGREQHWHUDSLMH ,62
Preparation and quality management of fluids for haemodialysis and related therapies -
Part 5: Quality of dialysis fluid for haemodialysis and related therapies (ISO 23500-
5:2019)
Vorbereitung und Qualitätsmanagement von Konzentraten für die Hämodialyse und
verwandte Therapien - Teil 5: Qualität von Flüssigkeiten für die Hämodialyse und
verwandte Therapien (ISO 23500-5:2019)
Préparation et management de la qualité des liquides d'hémodialyse et de thérapies
annexes - Partie 5: Qualité des liquides de dialyse pour hémodialyse et thérapies
apparentées (ISO 23500-5:2019)
Ta slovenski standard je istoveten z: EN ISO 23500-5:2019
ICS:
11.120.99 Drugi standardi v zvezi s Other standards related to
farmacijo pharmaceutics
SIST EN ISO 23500-5:2019 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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SIST EN ISO 23500-5:2019
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SIST EN ISO 23500-5:2019
EN ISO 23500-5
EUROPEAN STANDARD
NORME EUROPÉENNE
March 2019
EUROPÄISCHE NORM
ICS 11.040.40 Supersedes EN ISO 11663:2015
English Version
Preparation and quality management of fluids for
haemodialysis and related therapies - Part 5: Quality of
dialysis fluid for haemodialysis and related therapies (ISO
23500-5:2019)
Préparation et management de la qualité des liquides Vorbereitung und Qualitätsmanagement von
d'hémodialyse et de thérapies annexes - Partie 5: Konzentraten für die Hämodialyse und verwandte
Qualité des liquides de dialyse pour hémodialyse et Therapien - Teil 5: Qualität von Flüssigkeiten für die
thérapies apparentées (ISO 23500-5:2019) Hämodialyse und verwandte Therapien (ISO 23500-
5:2019)
This European Standard was approved by CEN on 14 January 2019.
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, Serbia, 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: Rue de la Science 23, B-1040 Brussels
© 2019 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 23500-5:2019 E
worldwide for CEN national Members.
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SIST EN ISO 23500-5:2019
EN ISO 23500-5:2019 (E)
Contents Page
European foreword . 3
2
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SIST EN ISO 23500-5:2019
EN ISO 23500-5:2019 (E)
European foreword
This document (EN ISO 23500-5:2019) has been prepared by Technical Committee ISO/TC 150
"Implants for surgery" in collaboration with 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 September 2019, and conflicting national standards
shall be withdrawn at the latest by September 2019.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 11663:2015.
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, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 23500-5:2019 has been approved by CEN as EN ISO 23500-5:2019 without any
modification.
3
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SIST EN ISO 23500-5:2019
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SIST EN ISO 23500-5:2019
INTERNATIONAL ISO
STANDARD 23500-5
First edition
2019-02
Preparation and quality management
of fluids for haemodialysis and related
therapies —
Part 5:
Quality of dialysis fluid for
haemodialysis and related therapies
Préparation et management de la qualité des liquides d'hémodialyse
et de thérapies annexes —
Partie 5: Qualité des liquides de dialyse pour hémodialyse et thérapies
apparentées
Reference number
ISO 23500-5:2019(E)
©
ISO 2019
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SIST EN ISO 23500-5:2019
ISO 23500-5:2019(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2019
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
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Phone: +41 22 749 01 11
Fax: +41 22 749 09 47
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2019 – All rights reserved
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SIST EN ISO 23500-5:2019
ISO 23500-5:2019(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Requirements . 2
4.1 Microbiological contaminants in dialysis fluid . 2
4.1.1 General. 2
4.1.2 Microbiological requirements for standard dialysis fluid . 2
4.1.3 Microbiological requirements for ultrapure dialysis fluid . 2
4.1.4 Microbiological requirements for online prepared substitution fluid . 2
4.2 Chemical contaminants in dialysis fluid . 3
5 Tests for conformity with microbiological requirements . 3
5.1 Sampling . 3
5.2 Culture methods . 3
Annex A (informative) Rationale for the development and provisions of this document .5
Annex B (informative) Reference tables . 8
Bibliography .11
© ISO 2019 – All rights reserved iii
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SIST EN ISO 23500-5:2019
ISO 23500-5:2019(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.
This first edition cancels and replaces ISO 11663:2014, which has been technically revised. The main
changes compared to the previous edition are as follows:
— The document forms part of a revised and renumbered series dealing with the preparation and
quality management of fluids for haemodialysis and related therapies. The series comprise
ISO 23500-1 (previously ISO 23500), ISO 23500-2, (previously ISO 26722), ISO 23500-3, (previously
ISO 13959), ISO 23500-4, (previously ISO 13958), and ISO 23500-5, (previously ISO 11663).
A list of all parts in the ISO 23500 series can be found on the ISO website.
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.
iv © ISO 2019 – All rights reserved
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SIST EN ISO 23500-5:2019
ISO 23500-5:2019(E)
Introduction
Haemodialysis patients are directly exposed to large volumes of dialysis fluid, with the dialyser
membrane being the only barrier against transfer of hazardous contaminants from the dialysis fluid
to the patient. It has long been known that there could be hazardous contaminants in the water and
concentrates used to prepare the dialysis fluid. To minimize this hazard, ISO 23500-3 and ISO 23500-4
set forth quality requirements for the water and concentrates used to prepare dialysis fluid. However,
if the dialysis fluid is not prepared carefully, it could contain unacceptable levels of contaminants even
though it is prepared from water and concentrates, conforming to the requirements of ISO 23500-3
and ISO 23500-4. Further, the dialysis fluid might be used as the starting material for the online
preparation of fluids intended for infusion into the patient, for example, in therapies such as online
haemodiafiltration. For these reasons, this document for dialysis fluid quality was developed to
complement the existing International Standards for water and concentrates, ISO 23500-3 and
ISO 23500-4, respectively. Guidelines to aid the user in routinely meeting the requirements of this
document and ISO 23500-3 can be found in ISO 23500-1.
Within these International Standards, measurement techniques current at the time of preparation have
been cited. Other standard methods can be used, provided that such methods have been appropriately
validated and are comparable to the cited methods. The rationale for the development of this document
is given in Annex A.
This document reflects the conscientious efforts of healthcare professionals, patients, and medical
device manufacturers to develop recommendations for the quality of dialysis fluid. This document
is directed at the healthcare professionals involved in the management of dialysis facilities and the
routine care of patients treated in dialysis facilities, since they are responsible for the final preparation
of dialysis fluid. The recommendations contained in this document are not intended for regulatory
application.
This document aims to help protect haemodialysis patients from adverse effects arising from known
chemical and microbiological contaminants that can 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 applicable quality standards.
The concepts incorporated in this document should not be considered inflexible or static. The
requirements and 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.
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SIST EN ISO 23500-5:2019
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SIST EN ISO 23500-5:2019
INTERNATIONAL STANDARD ISO 23500-5:2019(E)
Preparation and quality management of fluids for
haemodialysis and related therapies —
Part 5:
Quality of dialysis fluid for haemodialysis and related
therapies
1 Scope
This document specifies minimum quality requirements for dialysis fluids used in haemodialysis and
related therapies.
This document includes dialysis fluids used for haemodialysis and haemodiafiltration, including
substitution fluid for haemodiafiltration and haemofiltration.
This document excludes the water and concentrates used to prepare dialysis fluid or the equipment
used in its preparation. Those areas are covered by other International Standards.
Sorbent-based dialysis fluid regeneration systems that regenerate and recirculate small volumes of
dialysis fluid, systems for continuous renal replacement therapy that use pre-packaged solutions, and
systems and solutions for peritoneal dialysis are excluded from this document.
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 23500-1, Preparation and quality management of fluids for haemodialysis and related therapies —
Part 1: General requirements
ISO 23500-3, Preparation and quality management of fluids for haemodialysis and related therapies —
Part 3: Quality of water for haemodialysis and related therapies
ISO 23500-4, Preparation and quality management of fluids for haemodialysis and related therapies —
Part 4: Concentrates for haemodialysis and related therapies
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 23500-1 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 http: //www .electropedia .org/
© ISO 2019 – All rights reserved 1
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SIST EN ISO 23500-5:2019
ISO 23500-5:2019(E)
4 Requirements
4.1 Microbiological contaminants in dialysis fluid
4.1.1 General
The requirements contained in this clause apply to a sample of the dialysis fluid collected at the inlet to
the dialyser or the reinfusion point.
4.1.2 Microbiological requirements for standard dialysis fluid
Standard dialysis fluid shall contain a total viable microbial count of less than 100 CFU/ml (when tested
in accordance with Clause 5) and an endotoxin concentration of less than 0,5 EU/ml (when tested in
accordance with Clause 5).
Action levels for the total viable microbial count and endotoxin concentration in dialysis fluid should
also be set based on knowledge of the microbial dynamics of the system. Typically, the action levels are
set at 50 % of the maximum allowable levels for total viable microbial count and endotoxin; other levels
can be set.
If microbial counts exceeding the action levels are observed in the dialysis fluid, corrective measures,
such as disinfection and retesting, should be taken promptly to reduce the levels.
Associated with the presence of bacteria and endotoxin in dialysis fluid is the likely presence of fungi
(yeasts and filamentous fungi). After extensive discussion, the working group has not recommended
maximum limits, for such contaminants.
Tests for bacterial growth and endotoxins are not required if the dialysis machine fluid pathway is
fitted with an appropriate capacity bacteria-retentive and endotoxin-retentive filter validated by the
manufacturer and operated and surveilled according to the manufacturer's instructions, unless the
manufacturer requires such tests in the instructions for use.
4.1.3 Microbiological requirements for ultrapure dialysis fluid
Ultrapure dialysis fluid shall contain a total viable microbial count of less than 0,1 CFU/ml (when tested
in accordance with Clause 5) and an endotoxin concentration less than 0,03 EU/ml (when tested in
accordance with Clause 5). If those limits are exceeded in ultrapure dialysis fluid, corrective measures
should be taken to reduce the levels to an acceptable level. The user is responsible for surveilling the
dialysis fluid bacteriology of the system following installation. It is incumbent on the user to establish a
regular surveillance routine.
Tests for bacterial growth and endotoxins are not required if the dialysis machine fluid pathway is
fitted with an appropriate capacity bacteria-retentive and endotoxin-retentive filter validated by the
manufacturer and operated and surveilled according to the manufacturer's instructions, unless the
manufacturer requires such tests in the instructions for use.
4.1.4 Microbiological requirements for online prepared substitution fluid
The requirements contained in this clause apply to online prepared fluid intended to be infused into the
patient as it enters the patient's blood.
This fluid shall be sterile and nonpyrogenic.
Substitution fluid for convective therapies, such as haemodiafiltration and haemofiltration, can be
produced online by a process of ultrafiltration with bacteria-retentive and endotoxin-retentive filters.
This online process shall be validated to produce fluid that is sterile and nonpyrogenic.
Conformity of online produced fluid with the requirements of this document cannot be demonstrated
with traditional test procedures. For this reason, conformity with this document shall be ensured by
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SIST EN ISO 23500-5:2019
ISO 23500-5:2019(E)
proper operation of a validated system, verified according to the manufacturer's instructions at the
time of installation, and confirmed by the user with a regular surveillance and maintenance schedule.
The user shall follow the manufacturer’s instructions for use of the validated system, and the user’s
surveillance and maintenance schedule shall be designed to confirm that the water and concentrates
used to prepare the substitution fluid continue to meet the specifications of ISO 23500-3 and
ISO 23500-4.
4.2 Chemical contaminants in dialysis fluid
Dialysis fluid shall be prepared from water meeting the requirements of ISO 23500-3 and acid and
bicarbonate concentrates meeting the requirements of ISO 23500-4. The water and concentrates shall
be combined using individual dialysis fluid delivery systems or a central dialysis fluid delivery system
constructed from materials that do not contribute chemical contaminants to the final dialysis fluid.
The maximum levels of chemical contaminants permitted in water used to prepare dialysis fluid and
concentrates are given in ISO 23500-3 and are also shown in informative Annex B of this document
(Tables B.1 and B.2) together with methods of determination (Table B.3). Other equivalent analytical
methods can be used. Where testing for the individual trace elements listed in Table B.2 is not available,
an analysis for total heavy metals can be used with a maximum allowable level of at 0,1 mg/l.
5 Tests for conformity with microbiological requirements
5.1 Sampling
In some newer dialysis machines, dialysis fluid flow stops when the effluent line is disconnected from
the dialyser. In these instances, the machines are equipped with dialysis fluid sampling ports that can
be accessed using a syringe. Sample ports can be disinfected with alcohol and allowed to air-dry. A
sterile syringe should be used to aspirate at least 10 ml of dialysis fluid out of the sampling port. The
filled syringe is discarded and a fresh sample of dialysis fluid collected using a new sterile syringe. For
sample ports consisting of a simple septum penetrated with a needle, the use of a second syringe is not
necessary. Alternatively, if the dialysis machine permits, samples can be collected immediately before
the dialyser by disconnecting the inlet connector and aseptically collecting a “free/clean” catch sample
after allowing dialysis fluid to run for at least 60 s unless manufacturers’ instructions state otherwise.
Microbial analysis of any fluid sample should be conducted as soon as possible after collection to
avoid unpredictable changes in the microbial population. If samples cannot be analysed within 4 h of
collection, they should be stored at <10 °C without freezing and during transit to the laboratory. Sample
storage for more than 24 h should be avoided, and sample shipping should be in accordance with the
laboratory’s instructions.
5.2 Culture methods
Accurate microbiological surveillance is important in the indication of the microbial content of dialysis
water and dialysis fluid. Culture results obtained using the methods outlined in this document and
summarized in Table 1 are only a relative indicator of the bioburden and do not provide an absolute
measure of the absolute bacterial burden.
Total viable microbial counts (standard plate counts) shall be obtained using conventional
microbiological assay procedures (pour plate, spread plate, membrane filter techniques). The calibrated
loop technique shall not be used.
Preferred methods and sample volumes:
Standard dialysis fluid:
— spread plate, 0,1 ml to 0,3 ml;
— pour plate, typically 1 ml.
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SIST EN ISO 23500-5:2019
ISO 23500-5:2019(E)
Ultrapure dialysis fluid:
— membrane filtration, 10 ml to 1 000 ml.
Substitution fluid:
— sterility cannot be proven by sampling.
Different media types and incubation periods can result in varying colony concentrations and types of
microorganisms recovered.
The use of Reasoner’s 2A agar (R2A) has been shown in previous studies to result in higher colony
[6][7]
counts than tryptic soy agar (TSA) for water and dialysis fluids samples . In a more recent
[8]
publication, 2016 , the authors indicated that there were no significant differences for comparisons of
bacterial burden of standard dialysis water and standard dialysis fluid yielding colony counts ≥50 CFU/
ml when assayed using R2A and TSA at the conditions stated in Table 1.
Tryptone glucose extract agar (TGEA) incubated at 17 °C to 23 °C for a period of 7 days in previous
[9]
studies also yielded higher colony counts than TSA . Maltais et al. in their comparison of this medium
with TSA showed that the proportion of standard dialysis water samples yielding colony counts
≥50 CFU/ml was significantly different from that found using TSA at an incubation temperature of
35 °C to 37 °C and an incubation time of 48 hours (p=0,001). The proportions of dialysis fluid samples
in which microbial burden was ≥50 CFU/ml were not significantly different on the two media and
[8]
incubation conditions .
The culture medium and incubation times selected should be based on the type of fluid to be analysed
e.g. standard dialysis fluid, water used in the preparation of standard dialysis fluid, ultrapure dialysis
fluid, water used for the preparation of ultrapure dialysis fluid or fluid used for on line therapies
such as haemodiafiltration. The method selected should be based on the analysis of the advantages,
disadvantages and sensitivity of each of the suggested methods. It should also ensure that patient
safety is safeguarded and allow for consideration of local laboratory working practices, and that local
regulatory and reimbursement requirements can be met.
Blood agar and chocolate agar shall not be used.
Table 1 — Culture techniques
Incubation
Culture medium Incubation time
temperature
Tryptone Glucose Extract Agar (TGEA) 17 °C to 23 °C 7 d
Reasoner's agar no. 2 (R2A) 17 °C to 23 °C 7 d
a
Tryptic Soy Agar (TSA) 35 °C to 37 °C 48 h
a
The use of TSA has been only validated for measurement of standard dialysis fluid.
Other medium, incubation conditions and colony counting times can be used provided it has been
demonstrated that such methods have been appropriately validated and are comparable to the cited
methods.
Currently there are no requirements for routine surveillance for the presence of fungi (i.e. yeasts and
filamentous fungi), however if quantification is required, membrane filtration is suggested as the
method for obtaining a sample suitable for analysis. For culture, Sabouraud or Malt Extract Agar (MEA)
are recommended.
The presence of endotoxins shall be determined by a Limulus amoebocyte lysate (LAL) assay or another
validated method.
Conformity with the microbial standards for ultrapure dialysis fluid and substitution fluid prepared
online with a validated system can be met by following the requirements and instructions of the
manufacturer of the dialysis fluid delivery system.
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SIST EN ISO 23500-5:2019
ISO 23500-5:2019(E)
Annex A
(informative)
Rationale for the development and provisions of this document
A.1 Microbiological contaminants in dialysis fluid
NOTE The information in this clause is intended to give the reader a historical perspective of how the
microbial limits were developed for this document.
Pyrogenic reactions are caused by lipopolysaccharides or endotoxins that are associated with gram-
negative bacteria. Furthermore, gram-negative water bacteria have been shown to have the capability
of multiplying rapidly in a variety of hospital-associated flui
...
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