Preparation and quality management of fluids for haemodialysis and related therapies - Part 3: Water for haemodialysis and related therapies (ISO 23500-3:2019)

This document specifies minimum requirements for water to be used in haemodialysis and related
therapies.
This document includes water to be used in the preparation of concentrates, dialysis fluids for
haemodialysis, haemodiafiltration and haemofiltration, and for the reprocessing of haemodialysers.
This document excludes the operation of water treatment equipment and the final mixing of treated
water with concentrates to produce dialysis fluid. Those operations are the sole responsibility of
dialysis professionals. This document does not apply to dialysis fluid regenerating systems.

Leitfaden für die Vorbereitung und das Qualitätsmanagement von Konzentraten für die Hämodialyse und verwandte Therapien - Teil 3: Wasser für die Hämodialyse und verwandte Therapien (ISO 23500-3:2019)

Dieses Dokument legt Mindestanforderungen an Wasser fest, das in der Hämodialyse und in verwandten Therapien verwendet werden soll.
Dieses Dokument erfasst Wasser, das in der Herstellung von Konzentraten, Dialysierflüssigkeiten für die Hämodialyse, die Hämodiafiltration, die Hämofiltration und die Wiederaufbereitung von Hämodialysatoren verwendet werden soll.
Dieses Dokument gilt nicht für den Betrieb von Wasseraufbereitungsanlagen und die endgültige Mischung von aufbereitetem Wasser mit Konzentraten, um Dialysierflüssigkeit herzustellen. Dafür ist allei¬nig das Dialyse Fachpersonal verantwortlich. Dieses Dokument gilt nicht für Dialysierflüssigkeits-Aufbereitungssysteme.

Préparation et management de la qualité des liquides d'hémodialyse et de thérapies annexes - Partie 3: Eau pour hémodialyse et thérapies apparentées (ISO 23500-3:2019)

Le présent document spécifie les exigences minimales pour l'eau utilisée dans le cadre d'hémodialyses et de thérapies apparentées.
Le présent document inclut l'eau utilisée pour la préparation des concentrés et des liquides de dialyse pour hémodialyse, hémodiafiltration et hémofiltration, ainsi que pour le retraitement des hémodialyseurs.
Le présent document exclut le fonctionnement de l'équipement de traitement de l'eau et le mélange final de l'eau traitée avec les concentrés pour produire le liquide de dialyse. Ces opérations relèvent de l'entière responsabilité des néphrologues. Le présent document ne concerne pas les systèmes de régénération des liquides de dialyse.

Priprava in vodenje kakovosti tekočin za hemodializo in podobne terapije - 3. del: Voda za hemodializo in podobne terapije (ISO 23500-3:2019)

Ta dokument vključuje vodo za pripravo koncentratov, dializnih tekočin za hemodializo, hemodiafiltracijo in hemofiltracijo ter ponovno obdelavo v hemodializatorjih. Ta dokument ne zajema postopka uporabe opreme za pripravo vode in končno mešanje pripravljene vode s koncentrati za proizvodnjo dializne tekočine. Za takšne postopke so izključno odgovorni strokovnjaki za dializo. Ta dokument se ne uporablja za sisteme za regeneracijo dializne tekočine.

General Information

Status
Published
Public Enquiry End Date
19-Jun-2017
Publication Date
08-Apr-2019
Technical Committee
Current Stage
6060 - National Implementation/Publication (Adopted Project)
Start Date
02-Apr-2019
Due Date
07-Jun-2019
Completion Date
09-Apr-2019

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SLOVENSKI STANDARD
SIST EN ISO 23500-3:2019
01-maj-2019
1DGRPHãþD
SIST EN ISO 13959:2016

3ULSUDYDLQYRGHQMHNDNRYRVWLWHNRþLQ]DKHPRGLDOL]RLQSRGREQHWHUDSLMHGHO

9RGD]DKHPRGLDOL]RLQSRGREQHWHUDSLMH ,62

Preparation and quality management of fluids for haemodialysis and related therapies -

Part 3: Water for haemodialysis and related therapies (ISO 23500-3:2019)

Leitfaden für die Vorbereitung und das Qualitätsmanagement von Konzentraten für die

Hämodialyse und verwandte Therapien - Teil 3: Wasser für die Hämodialyse und
verwandte Therapien (ISO 23500-3:2019)

Préparation et management de la qualité des liquides d'hémodialyse et de thérapies

annexes - Partie 3: Eau pour hémodialyse et thérapies apparentées (ISO 23500-3:2019)

Ta slovenski standard je istoveten z: EN ISO 23500-3:2019
ICS:
11.120.99 Drugi standardi v zvezi s Other standards related to
farmacijo pharmaceutics
SIST EN ISO 23500-3:2019 en

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

---------------------- Page: 1 ----------------------
SIST EN ISO 23500-3:2019
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SIST EN ISO 23500-3:2019
EN ISO 23500-3
EUROPEAN STANDARD
NORME EUROPÉENNE
March 2019
EUROPÄISCHE NORM
ICS 11.040.40 Supersedes EN ISO 13959:2015
English Version
Preparation and quality management of fluids for
haemodialysis and related therapies - Part 3: Water for
haemodialysis and related therapies (ISO 23500-3:2019)

Préparation et management de la qualité des liquides Leitfaden für die Vorbereitung und das

d'hémodialyse et de thérapies annexes - Partie 3: Eau Qualitätsmanagement von Konzentraten für die

pour hémodialyse et thérapies apparentées (ISO Hämodialyse und verwandte Therapien - Teil 3:

23500-3:2019) Wasser für die Hämodialyse und verwandte Therapien
(ISO 23500-3:2019)
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 23500-3:2019 E

worldwide for CEN national Members.
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SIST EN ISO 23500-3:2019
EN ISO 23500-3:2019 (E)
Contents Page

European foreword ....................................................................................................................................................... 3

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SIST EN ISO 23500-3:2019
EN ISO 23500-3:2019 (E)
European foreword

This document (EN ISO 23500-3:2019) 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 13959:2015.

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 23500-3:2019 has been approved by CEN as EN ISO 23500-3:2019 without any

modification.
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SIST EN ISO 23500-3:2019
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SIST EN ISO 23500-3:2019
INTERNATIONAL ISO
STANDARD 23500-3
First edition
2019-02
Preparation and quality management
of fluids for haemodialysis and related
therapies —
Part 3:
Water for haemodialysis and related
therapies
Préparation et management de la qualité des liquides d'hémodialyse
et de thérapies annexes —
Partie 3: Eau pour hémodialyse et thérapies apparentées
Reference number
ISO 23500-3:2019(E)
ISO 2019
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SIST EN ISO 23500-3:2019
ISO 23500-3:2019(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
CP 401 • Ch. de Blandonnet 8
CH-1214 Vernier, Geneva
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
---------------------- Page: 8 ----------------------
SIST EN ISO 23500-3:2019
ISO 23500-3:2019(E)
Contents Page

Foreword ........................................................................................................................................................................................................................................iv

Introduction ..................................................................................................................................................................................................................................v

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

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

3 Terms and definitions ..................................................................................................................................................................................... 1

4 Requirements .......................................................................................................................................................................................................... 1

4.1 Dialysis water quality requirements .................................................................................................................................... 1

4.2 Chemical contaminant requirements .................................................................................................................................. 2

4.2.1 General...................................................................................................................................................................................... 2

4.2.2 Organic Carbon, pesticides and other chemicals ................................................................................. 3

4.3 Dialysis water microbiological requirements .............................................................................................................. 3

5 Tests for microbiological and chemical requirements ................................................................................................. 4

5.1 Dialysis water microbiology ........................................................................................................................................................ 4

5.2 Microbial contaminant test methods ................................................................................................................................... 4

5.3 Chemical contaminants test methods ................................................................................................................................. 5

Annex A (informative) Rationale for the development and provisions of this document ............................8

Bibliography .............................................................................................................................................................................................................................16

© ISO 2019 – All rights reserved iii
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SIST EN ISO 23500-3:2019
ISO 23500-3:2019(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 13959:2014, 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 23500-3:2019
ISO 23500-3:2019(E)
Introduction

Assurance of adequate water quality is one of the most important aspects of ensuring a safe and

effective delivery of haemodialysis, haemodiafiltration, or haemofiltration.

This document contains minimum requirements, chemical and microbiological, for the water to be used

for preparation of dialysis fluids, concentrates, and for the reprocessing of haemodialysers and the

necessary steps to ensure conformity with those requirements.

Haemodialysis and related therapies such as haemodiafiltration can expose the patient to more than

500 l of water per week across the semi-permeable membrane of the haemodialyser or haemodiafilter.

Healthy individuals seldom have a weekly oral intake above 12 l. This over 40-fold increase in exposure

requires control and regular surveillance of water quality to avoid excesses of known or suspected

harmful substances. Since knowledge of potential injury from trace elements and contaminants of

microbiological origin over long periods is still growing and techniques for treating drinking water are

continuously developed, this document will evolve and be refined accordingly. The physiological effects

attributable to the presence of organic contaminants in dialysis water are important areas for research,

however, the effect of such contaminants on patients receiving regular dialysis treatment is largely

unknown, consequently no threshold values for organic contaminants permitted in water used for the

preparation of dialysis fluids, concentrates, and reprocessing of haemodialysers has been specified in

this revised document.

Within this document, measurement techniques current at the time of publication 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 final dialysis fluid is produced from concentrates or salts manufactured, packaged, and labelled

according to ISO 23500-4 mixed with water meeting the requirements of this document. Operation of

water treatment equipment and haemodialysis systems, including on-going surveillance of the quality

of water used to prepare dialysis fluids, and handling of concentrates and salts are the responsibility

of the haemodialysis facility and are addressed in ISO 23500-1. Haemodialysis professionals make

choices about the various applications (haemodialysis, haemodiafiltration, haemofiltration) and should

understand the risks of each and the requirements for safety for fluids used for each.

This document is directed towards manufacturers and providers of water treatment systems and also

to haemodialysis facilities.

The rationale for the development of this document is given in informative Annex A.

© ISO 2019 – All rights reserved v
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SIST EN ISO 23500-3:2019
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SIST EN ISO 23500-3:2019
INTERNATIONAL STANDARD ISO 23500-3:2019(E)
Preparation and quality management of fluids for
haemodialysis and related therapies —
Part 3:
Water for haemodialysis and related therapies
1 Scope

This document specifies minimum requirements for water to be used in haemodialysis and related

therapies.

This document includes water to be used in the preparation of concentrates, dialysis fluids for

haemodialysis, haemodiafiltration and haemofiltration, and for the reprocessing of haemodialysers.

This document excludes the operation of water treatment equipment and the final mixing of treated

water with concentrates to produce dialysis fluid. Those operations are the sole responsibility of

dialysis professionals. This document does not apply to dialysis fluid regenerating systems.

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
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/
4 Requirements
4.1 Dialysis water quality requirements

The quality of the dialysis water, as specified in 4.2 and 4.3, shall be verified upon installation of a water

treatment system. Regular surveillance of the dialysis water quality shall be carried out thereafter.

NOTE Throughout this document it is assumed that the water undergoing treatment is potable water and

therefore meets the appropriate regulatory requirements for such water. If the water supply is derived from

an alternate source such as a privately-owned borehole or well, contaminant levels cannot be as rigorously

controlled.
© ISO 2019 – All rights reserved 1
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SIST EN ISO 23500-3:2019
ISO 23500-3:2019(E)
4.2 Chemical contaminant requirements
4.2.1 General

Dialysis water shall not contain chemicals at concentrations in excess of those listed in Tables 1 and

2, or as required by national legislation or regulations. Table 1 does not include any recommendation

in respect of organic carbon, pesticides and other chemicals such as pharmaceutical products and

endocrine disruptors that can be present in feed water. It is technically difficult and costly to measure

such substances on a routine basis. The effect of their presence on haemodialysis patients is difficult

to define and consequences of exposure are probably of a long-term nature. Furthermore, there is an

absence of evidence of their widespread presence in water although it is recognized that inadvertent

discharges are possible. In view of this, it is not at present possible to define limits for their presence in

water used in the preparation of dialysis fluid.

Nanofiltration and reverse osmosis are capable of significant rejection of many such compounds.

Granular Activated Carbon (GAC) is also highly effective at removing majority of these chemicals.

However, as Granular Activated Carbon is widely used in the removal chlorine/chloramine, their use in

the removal or organic carbons, pesticides and other chemicals will be dependent upon the size of the

carbon filters and/or beds and users shall be aware of appropriate dimensioning since the majority of

carbon valences can be already occupied and not available for further removal activity.

NOTE 1 See A.3 for an explanation of values supplied.

NOTE 2 The maximum allowable levels of contaminants listed in Tables 1 and 2 include the anticipated

uncertainty associated with the analytical methodologies listed in Table 4.

Where the dialysis water is used for the reprocessing of haemodialysers (cleaning, testing, and mixing

of disinfectants), the user is cautioned that the dialysis water shall meet the requirements of this

document. The dialysis water should be measured at the input to the dialyser reprocessing equipment.

Table 1 — Maximum allowable levels of toxic chemicals and dialysis fluid electrolytes in

dialysis water
Maximum concentration
Contaminant
Contaminants with documented toxicity in haemodialysis
Aluminium 0,01
Total chlorine 0,1
Copper 0,1
Fluoride 0,2
Lead 0,005
Nitrate (as N) 2
Sulfate 100
Zinc 0,1

A physician in charge of dialysis has ultimate responsibility for ensuring the quality of

water used for dialysis.
Unless otherwise indicated.

When chlorine is added to water, some of the chlorine reacts with organic materials and

metals in the water and is not available for disinfection (the chlorine demand of the water).

The remaining chlorine is the total chlorine, and is the sum of free or non bound chlorine and

combined chlorine.

There is no direct method for the measurement of chloramine. It is generally established by

measuring total and free chlorine concentrations and calculating the difference. When total

chlorine tests are used as a single analysis the maximum level for both chlorine and chloramine

shall not exceed 0,1 mg/l. Since there is no distinction between chlorine and chloramine, this

safely assumes that all chlorine present is chloramine.
2 © ISO 2019 – All rights reserved
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SIST EN ISO 23500-3:2019
ISO 23500-3:2019(E)
Table 1 (continued)
Maximum concentration
Contaminant
Electrolytes normally included in dialysis fluid
Calcium 2 (0,05 mmol/l)
Magnesium 4 (0,15 mmol/l)
Potassium 8 (0,2 mmol/l)
Sodium 70 (3,0 mmol/l)

A physician in charge of dialysis has ultimate responsibility for ensuring the quality of

water used for dialysis.
Unless otherwise indicated.

When chlorine is added to water, some of the chlorine reacts with organic materials and

metals in the water and is not available for disinfection (the chlorine demand of the water).

The remaining chlorine is the total chlorine, and is the sum of free or non bound chlorine and

combined chlorine.

There is no direct method for the measurement of chloramine. It is generally established by

measuring total and free chlorine concentrations and calculating the difference. When total

chlorine tests are used as a single analysis the maximum level for both chlorine and chloramine

shall not exceed 0,1 mg/l. Since there is no distinction between chlorine and chloramine, this

safely assumes that all chlorine present is chloramine.
Table 2 — Maximum allowable levels of other trace elements in dialysis water
Maximum concentration
Contaminant
mg/l
Antimony 0,006
Arsenic 0,005
Barium 0,1
Beryllium 0,000 4
Cadmium 0,001
Chromium 0,014
Mercury 0,000 2
Selenium 0,09
Silver 0,005
Thallium 0,002
4.2.2 Organic Carbon, pesticides and other chemicals

The presence of organic compounds, such as pesticides, polycyclic aromatic hydrocarbons and other

chemicals such as pharmaceutical products and endocrine disruptors in respect of haemodialysis

patients are difficult to define. Consequences of exposure are probably of a long-term nature and it is

technically difficult and costly to measure these substances on a routine basis. Furthermore, there is

an absence of evidence of their widespread presence in water although it is recognized that inadvertent

discharges are possible. In view of this, it is at present not possible to define limits for their presence in

water used in the preparation of dialysis fluid.
4.3 Dialysis water microbiological requirements

Total viable microbial counts in dialysis water shall be less than 100 CFU/ml, or lower if required by

national legislation or regulations. An action level shall be set based on knowledge of the microbial

dynamics of the system. Typically, the action level will be 50 % of the maximum allowable level.

Endotoxin content in dialysis water shall be less than 0,25 EU/ml, or lower if required by national

legislation or regulations. An action level shall be set, typically at 50 % of the maximum allowable level.

© ISO 2019 – All rights reserved 3
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SIST EN ISO 23500-3:2019
ISO 23500-3:2019(E)

Fungi (yeasts and filamentous fungi) can coexist with bacteria and endotoxin in the dialysis water.

Further studies on the presence of fungi in haemodialysis water systems, their role in biofilm formation

and their clinical significance are required and in view of this, no recommendation in respect of

permitted maximum limits is made.
NOTE See A.4 for a history of these requirements.
5 Tests for microbiological and chemical requirements
5.1 Dialysis water microbiology

Samples shall be collected where a dialysis machine connects to the water distribution loop, and from a

sample point in the distal segment of the loop or where such water enters a mixing tank.

Samples should be analysed 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 until ready to transport to the laboratory for analysis. Sample storage for

more than 24 h should be avoided, and sample shipping should be in accordance with the laboratory’s

instructions.

Total viable counts (standard plate counts) shall be obtained using conventional microbiological assay

procedures (pour plate, spread plate, membrane filter techniques). Membrane filtration is the preferred

method for this test. Other methods may be used, provided that such methods have been appropriately

validated and are comparable to the cited methods. The use of the calibrated loop technique is not

acceptable.
5.2 Microbial contaminant test methods

Methodology to establish microbial contaminant levels is given in Table 3. Such methods provide only a

relative indication of the bacterial bioburden rather than an absolute measure.

Recommended methods and cultivation conditions can also be found in ISO 23500-4 and ISO 23500-5 as

well as this document (Table 3). The methodology detailed uses Tryptone Glucose Extract Agar (TGEA)

and Reasoner’s Agar No. 2 (R2A) incubated at 17 °C to 23 °C for a period of 7 days and Tryptic Soy Agar

[8]

(TSA) at an incubation temperature of 35 °C to 37 °C and an incubation time of 48 h . The background

for the inclusion of TSA for standard water and standard dialysis fluid used for standard dialysis is

explained in detail in A.4.

Different media types and incubation periods can result in varying colony concentrations and types of

[8][9][10]

microorganisms recovered . The use of Reasoner’s 2A agar (R2A) has been shown in previous

studies to result in higher colony counts than tryptic soy agar (TSA) for water and dialysis fluids

[10][11][12]

samples . In a more recent publication, in 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

[8]
stated in the preceding paragraph of this subclause .

Historic studies with tryptone glucose extract agar (TGEA) incubated at 17 °C to 23 °C for a period

[13] [8]

of 7 days 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 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 online therapies

such as haemodiafiltration. The method selected, should be based on the analysis of the advantages,

disadvantages and sensitivity, of each of the methods detailed above. According to the United States

4 © ISO 2019 – All rights reserved
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SIST EN ISO 23500-3:2019
ISO 23500-3:2019(E)

Pharmacopeia, “the decision to use longer incubation times", should be made after balancing the need

for timely information and the type of corrective actions required when alert or action level is exceeded

with the ability to recover the microorganisms of interest. The advantages gained by incubating

for longer times namely recovery of injured microorganisms, slow growers, or more fastidious

microorganisms, should be balanced against the need to have a timely investigation and take corrective

action, as well as the ability of these microorganisms to detrimentally affect products or processes”

[e.g. patient safety].

Other methods may be used, provided that such methods have been appropriately validated and are

comparable to the cited methods. Blood agar and chocolate agar shall not be used.

Currently there are no requirements for routine surveillance for the presence of fungi (i.e. yeasts

and filamentous fungi) which can coexist with other microbial species, however if indication of their

presence is required, membrane filtration is the preferred method for the provision of a sample

suitable for analysis. Culture media used should be Sabouraud, or Malt Ex
...

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