ISO/DIS 23500

Fluids for haemodialysis and related therapies

Fluides d'hémodialyse et de thérapies annexes

Standards Content (sample)

DRAFT INTERNATIONAL STANDARD ISO/DIS 23500
ISO/TC 150/SC 2 Secretariat: ANSI
Voting begins on: Voting terminates on:
2006-03-22 2006-08-22

INTERNATIONAL ORGANIZATION FOR STANDARDIZATION • МЕЖДУНАРОДНАЯ ОРГАНИЗАЦИЯ ПО СТАНДАРТИЗАЦИИ • ORGANISATION INTERNATIONALE DE NORMALISATION

Fluids for haemodialysis and related therapies
Fluides d'hémodialyse et de thérapies annexes
ICS 11.040.40

In accordance with the provisions of Council Resolution 15/1993 this document is circulated in

the English language only.

Conformément aux dispositions de la Résolution du Conseil 15/1993, ce document est distribué

en version anglaise seulement.

To expedite distribution, this document is circulated as received from the committee secretariat.

ISO Central Secretariat work of editing and text composition will be undertaken at publication

stage.

Pour accélérer la distribution, le présent document est distribué tel qu'il est parvenu du

secrétariat du comité. Le travail de rédaction et de composition de texte sera effectué au

Secrétariat central de l'ISO au stade de publication.

THIS DOCUMENT IS A DRAFT CIRCULATED FOR COMMENT AND APPROVAL. IT IS THEREFORE SUBJECT TO CHANGE AND MAY NOT BE

REFERRED TO AS AN INTERNATIONAL STANDARD UNTIL PUBLISHED AS SUCH.

IN ADDITION TO THEIR EVALUATION AS BEING ACCEPTABLE FOR INDUSTRIAL, TECHNOLOGICAL, COMMERCIAL AND USER PURPOSES, DRAFT

INTERNATIONAL STANDARDS MAY ON OCCASION HAVE TO BE CONSIDERED IN THE LIGHT OF THEIR POTENTIAL TO BECOME STANDARDS TO

WHICH REFERENCE MAY BE MADE IN NATIONAL REGULATIONS.
© International Organization for Standardization, 2006
---------------------- Page: 1 ----------------------
ISO/DIS 23500
PDF disclaimer

This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but shall

not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In

downloading this file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat

accepts no liability in this area.
Adobe is a trademark of Adobe Systems Incorporated.

Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation

parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In the

unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.

Copyright notice

This ISO document is a Draft International Standard and is copyright-protected by ISO. Except as permitted

under the applicable laws of the user's country, neither this ISO draft nor any extract from it may be

reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, photocopying,

recording or otherwise, without prior written permission being secured.

Requests for permission to reproduce should be addressed to 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 [e-mail]
Web www.iso.org
Reproduction may be subject to royalty payments or a licensing agreement.
Violators may be prosecuted.
ii ISO 2006 – All rights reserved
---------------------- Page: 2 ----------------------
ISO/DIS 23500
Contents
Page

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

1.1 General ........................................................................................................................................................1

1.2 Inclusions ....................................................................................................................................................1

1.3 Exclusions...................................................................................................................................................1

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

3 Definitions ...................................................................................................................................................1

4 Requirements..............................................................................................................................................7

4.1 Water............................................................................................................................................................7

4.1.1 General ........................................................................................................................................................7

4.1.2 Requirements for chemical contaminants in water..................................................................................7

4.1.3 Requirements for microbial contaminates in water .................................................................................9

4.2 Requirements for concentrate ...................................................................................................................9

4.2.1 Requirements for chemical and microbiological contaminants in concentrate ....................................9

4.2.2 Requirements for bicarbonate concentrate ..............................................................................................9

4.2.3 Requirements for water used to prepare concentrate .............................................................................9

4.3 Requirements for dialysate ........................................................................................................................9

4.3.1 Microbiological contaminates in dialysate ...............................................................................................9

4.4 Record retention .......................................................................................................................................10

5 Monitoring .................................................................................................................................................10

5.1 General ......................................................................................................................................................10

5.2 Water purification monitoring..................................................................................................................13

5.2.1 General ......................................................................................................................................................13

5.2.2 Monitoring of sediment filters..................................................................................................................13

5.2.3 Monitoring of cartridge filters ..................................................................................................................13

5.2.4 Monitoring of softeners ............................................................................................................................14

5.2.5 Monitoring of carbon adsorption.............................................................................................................14

5.2.6 Monitoring of chemical injection systems ..............................................................................................14

5.2.7 Monitoring of reverse osmosis................................................................................................................15

5.2.8 Monitoring of deionization .......................................................................................................................15

5.2.9 Monitoring of ultrafiltration ......................................................................................................................15

5.3 Monitoring of water storage and distribution .........................................................................................16

5.3.1 General ......................................................................................................................................................16

5.3.2 Monitoring of water distribution systems ...............................................................................................16

5.3.3 Bacterial control devices..........................................................................................................................16

5.4 Concentrate preparation ..........................................................................................................................17

5.4.1 Monitoring of mixing systems .................................................................................................................17

5.4.2 Monitoring of additives.............................................................................................................................17

5.5 Monitoring of concentrate distribution ...................................................................................................17

5.6 Monitoring of dialysate proportioning.....................................................................................................18

6 Strategies for microbiological control.....................................................................................................18

6.1 General ......................................................................................................................................................18

6.2 Disinfection ...............................................................................................................................................18

6.2.1 Design of fluid systems............................................................................................................................19

6.2.2 Verification of proper operation...............................................................................................................19

6.3 Microbiological monitoring methods ......................................................................................................19

6.3.1 General ......................................................................................................................................................19

6.3.2 Sample collection......................................................................................................................................20

6.3.3 Heterotrophic plate count.........................................................................................................................20

6.3.4 Bacterial endotoxin test ...........................................................................................................................21

7 Environment..............................................................................................................................................22

8 Personnel...................................................................................................................................................22

Annex A (informative), Rationale for the development and provisions of this International Standard ..........23

Annex B (informative), Equipment .......................................................................................................................30

© ISO:2006 – All rights reserved
iii
---------------------- Page: 3 ----------------------
ISO/DIS 23500

Annex C (informative), Strategies for microbiological control...........................................................................44

Bibliography...........................................................................................................................................................48

© ISO:2006 – All rights reserved
---------------------- Page: 4 ----------------------
ISO/DIS 23500
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 nongovernmental, 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.

International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.

The main task of technical committees is to prepare International Standards. Draft International Standards adopted

by the technical committees are circulated to the member bodies for voting. Publication as an International

Standard requires approval by at least 75 % of the member bodies casting a vote.

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.

ISO 23500 was prepared by Technical Committee ISO/TC 150 Subcommittee SC 2, Cardiovascular implants and

extracorporeal systems.
© ISO:2006 – All rights reserved
---------------------- Page: 5 ----------------------
ISO/DIS 23500
Introduction

This International Standard was developed by the Technical Committee of ISO/TC 150/SC 2 WG5. The Working

Group's objective is to provide rational guidelines for handling water and concentrates and for the production and

monitoring of dialysate used for haemodialysis. The need for such guidelines is based on the critical role of

dialysate quality in providing safe and effective haemodialysis, and the recognition that day-to-day dialysate quality

is under the control of the health care professionals who deliver dialysis therapy.

This International Standard reflects the conscientious efforts of health care professionals, patients, and medical

device manufacturers to develop recommendations for handling water and concentrates and for the production and

monitoring of dialysate for haemodialysis. This international standard is directed towards the healthcare

professionals involved in the management of dialysis facilities and healthcare professionals involved in the routine

care of patients treated in dialysis facilities.The recommendations contained in this document may not be

applicable in all circumstances and they are not intended for regulatory application.

The use to which the water is put is not within the control of the equipment or equipment provider, thus, this

standard cannot address the clinical issues that may be associated with inappropriate usage of the product water

and the final dialysate. Healthcare professionals involved in the provision of treatment for renal failure must make

the final decision regarding the applications with which the water provided is used for, e.g. haemodialysis,

haemodiafiltration, high flux dialysis, and the reprocessing of dyalisers, and need to be aware of the issues that the

use of inappropriate water quality raises in each of the therapies.

The equipment used in the various stages of dialysate preparation is generally obtained from specialized vendors.

This International Standard provides a general description of the system components that these vendors may

provide. These descriptions are intended to provide the user with a basis for understanding why certain equipment

may be required and how it should be configured; they are not intended as detailed design standards. Dialysis

practitioners are generally responsible for maintaining the equipment used to prepare dialysate following its

installation. Therefore, this International Standard provides guidance on monitoring and maintenance of the

equipment to ensure that dialysate 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.

The guidance provided by this International Standard should help protect haemodialysis patients from adverse

effects arising from known chemical and microbial contaminants that may be found in improperly prepared

dialysate. However, the physician in charge of dialysis has the ultimate responsibility for ensuring that the dialysate

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 dialysate purity in patient outcomes and technological developments.
© ISO:2006 – All rights reserved
---------------------- Page: 6 ----------------------
Draft International Standard ISO/DIS 23500
Fluids for haemodialysis and related therapies
1 Scope
1.1 General

The intent of this International Standard is to provide dialysis practitioners with guidance on the preparation of

dialysate for haemodialysis and related therapies, from the point at which municipal water enters their dialysis

facility to the point at which the final dialysate enters the dyaliser, and as such functions as a recommended

practice. Included in the scope of the International Standard are: (1) use, maintenance, and monitoring of

equipment used to purify and distribute water used for the preparation of dialysate and other haemodialysis

applications; (2) use, maintenance, and monitoring of equipment used to prepare concentrate from powder at a

dialysis facility; and (3) preparation of the final dialysate from purified water and concentrate.

1.2 Inclusions

This International Standard addresses the user’s responsibility for the dialysate once equipment has been

delivered and installed. For the purposes of this International Standard, the dialysate includes water used for the

preparation of dialysate, water used for the preparation of concentrates at the user’s facility, and water used for the

preparation of ultrapure dialysate, as well as the final dialysate and concentrates.

NOTE Because water used to prepare dialysate is commonly prepared and distributed using the same equipment as the water

used reprocess dyalisers, water used to reprocess dyalisers is also covered by this International Standard.

1.3 Exclusions

Excluded from the scope of this International Standard are sorbent-based dialysate regeneration systems that

regenerate and recirculate small volumes of dialysate, systems for continuous renal replacement therapy that use

prepackaged solutions, and systems and solutions for peritoneal dialysis.
2 Normative references

The following referenced documents are indispensable for the application 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 13959, Water for haemodialysis and related therapies
ISO 13958, Concentrates for haemodialysis and related therapies
3 Definitions

For the purposes of this International Standard, the following terms and definitions apply.

3.1
acetate concentrate

concentrated solution of salts that may contain glucose, which, when diluted with water, yields dialysate for use in

dialysis. Sodium acetate is normally used as the buffer
© ISO:2006 – All rights reserved
---------------------- Page: 7 ----------------------
ISO/DIS 23500
NOTE 1 This concentrate is used as a single concentrate.
NOTE 2 In some cases glucose is also known as dextrose.
3.2
acetate dialysate

dialysate without bicarbonate, using acetate as a substitute for the bicarbonate buffer

NOTE Acetate dialyzing fluid is generally produced from a single concentrate. Acetate is metabolized by the patient to produce

bicarbonate.
3.3
acid concentrate

acidified concentrated solution of salts that may contain glucose, which, when diluted with water and bicarbonate

concentrate, yields dialysate for use in dialysis

NOTE The term “acid” refers to the small amount of acid (usually acetic acid) that is included in the concentrate.

3.4
action level

concentration of a contaminant at which steps should be taken to interrupt the trend toward higher, unacceptable

levels
3.5
anions
ions carrying a negative charge
3.6
available chlorine
free CIO- ions, dissolved molecular chlorine
3.7
bacteriology

area of study within the field of microbiology that deals with the study of bacteria

3.8
batch system

apparatus in which the dialysate is prepared in bulk before each dialysis session

3.9
bicarbonate concentrate

concentrated solution of sodium bicarbonate that, when diluted with water and acid concentrate, makes dialysate

used for dialysis
NOTE 1 Some bicarbonate concentrates also contain sodium chloride.
NOTE 2 Bicarbonate is also known as Sodium hydrogen carbonate.
3.10
bicarbonate dialysate
dialysate containing physiological or higher concentrations of bicarbonate

NOTE Bicarbonate dialysate is generally produced from two concentrates: one containing bicarbonate and the other containing

acid and other electrolytes (see acid concentrate and bicarbonate concentrate).
3.11
bleach

a solution of sodium hypochlorite normally used for household cleaning and disinfection

© ISO:2006 – All rights reserved
---------------------- Page: 8 ----------------------
ISO/DIS 23500
3.12
biofilm

coating on surfaces that consists of microcolonies of bacteria embedded in a protective extracellular matrix. The

matrix, a slimy material secreted by the cells, protects the bacteria from antibiotics and chemical disinfectants

3.13
bulk delivery

delivery of large volumes of concentrate in which the product is transferred (pumped) from the delivery container to

a user’s storage tank
3.14
cations
ions carrying a positive charge
3.15
chlorine, combined
chlorine that is chemically combined, such as in chloramine compounds

NOTE 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.
3.16
chlorine, free
dissolved molecular chlorine
3.17
colony-forming unit (CFU)

organism capable of replicating to form a distinct, visible colony on a culture plate. In practice, a colony may be

formed by a group of organisms
3.18
concentrate generators

system in which the concentrate is delivered to the consumer as a powder in a container and then converted online

into a saturated solution by a dialysis delivery machine

NOTE This solution is used by an individual proportioning system to make the final dialysate delivered to the dyaliser.

3.19
dialysate

aqueous fluid containing electrolytes and, usually, glucose, which is intended to exchange solutes with blood during

haemodialysis

NOTE The word “dialysate” is used throughout this document to mean the fluid made from water and concentrates that is

delivered to the dyaliser by the dialysate supply system. Such phrases as "dialysis fluid," “dialyzing fluid” or “dialysis solution”

may be used in place of dialysate.
3.20
central dialysate delivery systems (CDS)

dialysate systems that produce dialysate at a central point and distribute the prepared dialysate to the dialysis

control station
3.21
dialysate supply system

devices that: (1) prepare dialysate online from water and concentrates or that store and distribute premixed

dialysate; (2) circulate the dialysate through the dyaliser; (3) monitor the dialysate for temperature, conductivity (or

equivalent), pressure, flow, and blood leaks; and (4) prevent dialysis during disinfection or cleaning modes

NOTE 1 The dialysate supply system includes reservoirs, conduits, proportioning devices for the dialysate, and monitors and

associated alarms and controls assembled as a system for the characteristics listed above.

NOTE 2 The dialysate supply system may be an integral part of the single patient dialysis machine or a centralized preparation

system which feeds multiple bedside monitoring systems.
© ISO:2006 – All rights reserved
---------------------- Page: 9 ----------------------
ISO/DIS 23500
3.22
disinfection

destruction of pathogenic and other kinds of microorganisms by thermal or chemical means

NOTE 1 Disinfection is a less lethal process than sterilization, because it destroys most recognized pathogenic microorganisms

but does not necessarily destroy all microbial forms.

NOTE 2 This definition of “disinfection” is equivalent to low-level disinfection in the Spalding classification.

3.23
electrolyte
ion capable of transferring or exchanging electrons

NOTE In dialysate, the electrolytes are the charged ions that result from dissociation of salts when they are dissolved in water.

These charged ions are responsible for the conductive property of dialysate.
3.24
empty-bed contact time (EBCT)

measure of how much contact occurs between particles, such as activated carbon, and water as the water flows

through a bed of the particles
NOTE
EBCT (min) is calculated from the following equation:
EBCT = V/Q
where
V is the volume of particles in the bed (meter );
Q is the flow rate of water through the bed (meter /min).
3.25
endotoxin
major component of the outer cell wall of gram-negative bacteria

NOTE Endotoxins are lipopolysaccharides, which consist of a polysaccharide chain covalently bound to lipid A. Endotoxins can

acutely activate both humoral and cellular host defenses, 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)

3.26
endotoxin units (EU)

units assayed by the Limulus amoebocyte lysate (LAL) method when testing for endotoxins

NOTE 1 Because activity of endotoxins differs on a mass basis, their reference to a standard E. coli endotoxin has been

established and is used to compare various lots of product.

NOTE 2 In some countries, endotoxin concentrations are expressed in international units (IU). Since the 1983

harmonization of endotoxin assays, EU and IU are equivalent.
3.27
feed water

water supplied to a water treatment system or an individual component of the system

3.28
germicide
agent that kills microorganisms
3.29
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
© ISO:2006 – All rights reserved
---------------------- Page: 10 ----------------------
ISO/DIS 23500

NOTE Diffusive solute removal is achieved using a dialysate 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 dyaliser (predilution haemodiafiltration) or after the dyaliser

(postdilution haemodiafiltration).
3.30
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 dialysate flowing on the other side

NOTE 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 higher

molecular weight solutes.
3.31
haemofiltration

form of renal replacement therapy in which waste solutes are removed from blood by convection

NOTE 1 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 (pre-dilution haemofiltration) or after the haemofilter

(post-dilution haemofiltration).
NOTE 2 There is no dialysate stream in haemofiltration.
3.32
heterotrophic

not self-sustaining; a type of nutrition in which organisms derive energy from the oxidation of organic compounds

either by consumption or absorption of other organisms
3.33
Limulus amoebocyte lysate (LAL) test
assay used to detect endotoxin

NOTE The detection method uses the chemical specific response of the horseshoe crab (Limulus polyphemus) to endotoxin.

3.34
manufacturer

person who designs, manufactures, fabricates, assembles, or processes a finished device

NOTE Manufacturers include, but are not limited to, those who perform the functions of contract sterilization, installation,

relabeling, remanufacturing, repacking, or specification development, and initial distributions of foreign entities performing these

functions.
3.35
microbial

referring to microscopic organisms, bacteria, fungi, and so forth (see also bacteriology)

3.36
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,
...