EN ISO 13958:2015

SLOVENSKI STANDARD
01-februar-2016
1DGRPHãþD
SIST EN 13867:2003+A1:2009
Koncentrati za hemodializo in podobne terapije (ISO 13958:2014)
Concentrates for haemodialysis and related therapies (ISO 13958:2014)
Konzentrate für Hämodialyse und ähnliche Therapien (ISO 13958:2014)
Concentrés pour hémodialyse et thérapies apparentées (ISO 13958:2014)
Ta slovenski standard je istoveten z: EN ISO 13958:2015
ICS:
11.120.99 Drugi standardi v zvezi s Other standards related to
farmacijo pharmaceutics
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 13958
EUROPEAN STANDARD
NORME EUROPÉENNE
December 2015
EUROPÄISCHE NORM
ICS 11.040.40 Supersedes EN 13867:2002+A1:2009
English Version
Concentrates for haemodialysis and related therapies (ISO
13958:2014)
Concentrés pour hémodialyse et thérapies apparentées Konzentrate für Hämodialyse und ähnliche Therapien
(ISO 13958:2014) (ISO 13958:2014)
This European Standard was approved by CEN on 23 November 2015.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

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

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels
© 2015 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 13958:2015 E
worldwide for CEN national Members.

Contents Page
European foreword . 3
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices . 5
European foreword
The text of ISO 13958:2014 has been prepared by Technical Committee ISO/TC 150 “Implants for
surgery” of the International Organization for Standardization (ISO) and has been taken over as EN
ISO 13958:2015 by Technical Committee CEN/TC 205 “Non-active medical devices” the secretariat of
which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by June 2016, and conflicting national standards shall be
withdrawn at the latest by June 2016.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent
rights.
This document supersedes EN 13867:2002+A1:2009.
This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).
For relationship with EU Directive(s), see informative Annex ZA, which is an integral part of this
document.
The following referenced documents are indispensable for the application of this document. For
undated references, the latest edition of the referenced document (including any amendments) applies.
For dated references, only the edition cited applies. However, for any use of this standard ‘within the
meaning of Annex ZA’, the user should always check that any referenced document has not been
superseded and that its relevant contents can still be considered the generally acknowledged state-of-
art.
When an IEC or ISO standard is referred to in the ISO standard text, this shall be understood as a
normative reference to the corresponding EN standard, if available, and otherwise to the dated version
of the ISO or IEC standard, as listed below.
NOTE The way in which these referenced documents are cited in normative requirements determines the
extent (in whole or in part) to which they apply.
Table 1 — Correlation between normative references and dated EN and ISO standards
Normative references Equivalent dated standard
as listed in Clause 2 of the ISO
EN ISO or IEC
standard
ISO 11663 ISO 11663:2014
EN ISO 11663:2015
ISO 13959 ISO 13959:2014
EN ISO 13959:2015
ISO 14971 EN ISO 14971:2012 ISO 14971:2007
IEC 60601-1 EN 60601- IEC 60601-
1:2006+Cor.:2010+A1:2013 1:2005+Cor.:2006+Cor.:2007+A1:2012
IEC 61010-1 EN 61010-1:2010 IEC 61010-1:2010+Cor.:2011
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta,
Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland,
Turkey and the United Kingdom.
Endorsement notice
The text of ISO 13958:2014 has been approved by CEN as EN ISO 13958:2015 without any modification.

1)
To be published
2)
To be published.
Annex ZA
(informative)
Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices
This European Standard has been prepared under a mandate given to CEN by the European
Commission and the European Free Trade Association to provide a means of conforming to Essential
Requirements of the New Approach Directive 93/42/EEC on medical devices.
Once this standard is cited in the Official Journal of the European Union under that Directive and has
been implemented as a national standard in at least one Member State, compliance with the clauses of
this standard given in Table ZA.1 confers, within the limits of the scope of this standard, a presumption
of conformity with the corresponding Essential Requirements of that Directive and associated EFTA
regulations.
NOTE 1 Where a reference from a clause of this standard to the risk management process is made, the risk
management process needs to be in compliance with Directive 93/42/EEC as amended by 2007/47/EC. This
means that risks have to be reduced ‘as far as possible’, ‘to a minimum’, ‘to the lowest possible level’, ‘minimized’
or ‘removed’, according to the wording of the corresponding essential requirement.
NOTE 2 The manufacturer’s policy for determining acceptable risk must be in compliance with essential
requirements 1, 2, 5, 6, 7, 8, 9, 11 and 12 of the Directive.
NOTE 3 This Annex ZA is based on normative references according to the table of references in the European
foreword, replacing the references in the core text.
NOTE 4 When an Essential Requirement does not appear in Table ZA.1, it means that it is not addressed by this
European Standard.
Table ZA.1 — Correspondence between this European Standard and Directive 93/42/EEC on
medical devices
Essential Requirements (ERs) of
Clause(s)/sub-clause(s) of this EN Qualifying remarks/Notes
Directive 93/42/EEC
6.3 7.2
6.4 7.3
5.3 7.5
4.1.4.2 8
4.1.10 8.3
4 8.6
4 9.1
4.2, 4.3 9.2
6 13.1
6.2, 6.3, 6.4 13.2
6.2, 6.3, 6.4 13.3. (a)
6.2, 6.3, 6.4 13.3. (b)
Essential Requirements (ERs) of
Clause(s)/sub-clause(s) of this EN Qualifying remarks/Notes
Directive 93/42/EEC
6.2, 6.3, 6.4 13.3. (d)
6.2, 6.3, 6.4 13.3. (e)
6.2, 6.3, 6.4 13.3. (g)
6.2, 6.3, 6.4 13.3. (i)
6.2, 6.3, 6.4 13.3. (j)
6.2, 6.3, 6.4 13.3. (k)
6.2, 6.3, 6.4 13.3. (l)
6.2, 6.3, 6.4 13.4
6.2, 6.3, 6.4 13.6. (q)
WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling
within the scope of this standard.
INTERNATIONAL ISO
STANDARD 13958
Third edition
2014-04-01
Concentrates for haemodialysis and
related therapies
Concentrés pour hémodialyse et thérapies apparentées
Reference number
ISO 13958:2014(E)
©
ISO 2014
ISO 13958:2014(E)
© ISO 2014
All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form
or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior
written permission. Permission can be requested from either ISO at the address below or ISO’s member body in the country of
the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail copyright@iso.org
Web www.iso.org
Published in Switzerland
ii © ISO 2014 – All rights reserved

ISO 13958:2014(E)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Requirements . 7
4.1 Concentrates . 7
4.2 Manufacturing equipment . 9
4.3 Systems for mixing concentrate at a dialysis facility . 9
5 Tests .11
5.1 General .11
5.2 Concentrates .11
5.3 Manufacturing equipment .13
5.4 Systems for mixing concentrate at a dialysis facility .13
6 Labelling .14
6.1 General .14
6.2 General labelling requirements for concentrates .15
6.3 Labelling requirements for liquid concentrate .16
6.4 Labelling requirements for powder concentrate .16
6.5 Additives .17
6.6 Labelling requirements for concentrate generators .17
6.7 Labelling for concentrate mixer systems .18
Annex A (informative) Rationale for the development and provisions of this
International Standard .20
Bibliography .25
ISO 13958:2014(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical Barriers
to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This third edition cancels and replaces the second edition (ISO 13958:2009), which has been technically
revised.
iv © ISO 2014 – All rights reserved

ISO 13958:2014(E)
Introduction
The requirements and goals established by this International Standard will help ensure the effective,
safe performance of haemodialysis concentrates and related materials. This International Standard
reflects the conscientious efforts of concerned physicians, clinical engineers, nurses, dialysis technicians
and dialysis patients, in consultation with device manufacturers and government representatives, to
develop a standard for performance levels that could be reasonably achieved at the time of publication.
The term “consensus” as applied to the development of voluntary medical device standards does not
imply unanimity of opinion, but rather reflects the compromise necessary in some instances when a
variety of interests must be merged.
Throughout this International Standard, recommendations are made to use ISO-quality water. Therefore,
it is recommended to review ISO 13959 along with this International Standard.
This International Standard does not cover the dialysis fluid that is used to clinically dialyse patients.
Dialysis fluid is covered in ISO 11663. The making of dialysis fluid involves the proportioning of
concentrate and water at the bedside or in a central dialysis fluid delivery system. Although the label
requirements for dialysis fluid are placed on the labelling of the concentrate, it is the user’s responsibility
to ensure proper use.
In addition, this International Standard does not cover haemodialysis equipment, which is addressed in
IEC 60601-2-16:2012.
The verbal forms used in this International Standard conform to usage described in Annex H of the
ISO/IEC Directives, Part 2. For the purposes of this International Standard, the auxiliary verb
— “shall” means that compliance with a requirement or a test is mandatory for compliance with this
International Standard,
— “should” means that compliance with a requirement or a test is recommended but is not mandatory
for compliance with this International Standard, and
— “may” is used to describe a permissible way to achieve compliance with a requirement or test.
INTERNATIONAL STANDARD ISO 13958:2014(E)
Concentrates for haemodialysis and related therapies
1 Scope
This International Standard specifies minimum requirements for concentrates used for haemodialysis
and related therapies. For the purpose of this International Standard, “concentrates” are a mixture of
chemicals and water, or chemicals in the form of dry powder or other highly concentrated media, that
are delivered to the end user to make dialysis fluid used to perform haemodialysis and related therapies.
This International Standard is addressed to the manufacturer of such concentrates. In several instances
in this International Standard, it became necessary to address the dialysis fluid, which is made by the
end user, to help clarify the requirements for manufacturing concentrates. Because the manufacturer
of the concentrate does not have control over the final dialysis fluid, any reference to dialysis fluid is for
clarification and is not a requirement of the manufacturer.
This International Standard includes concentrates in both liquid and powder forms. Also included are
additives, also called spikes, which are chemicals that may be added to the concentrate to increase the
concentration of one or more of the existing ions in the concentrate and thus in the final dialysis fluid.
This International Standard also gives requirements for equipment used to mix acid and bicarbonate
powders into concentrate at the user’s facility.
Concentrates prepared from prepackaged salts and water at a dialysis facility for use in that facility
are excluded from the scope of this International Standard. Although references to dialysis fluid appear
herein, this International Standard does not address dialysis fluid as made by the end user. Also excluded
from the scope of this International Standard are requirements for the monitoring frequency of water
purity used for the making of dialysis fluid by the dialysis facility. Recommendations from the technical
committee responsible for this International Standard for monitoring water quality are contained in
ISO 23500. This International Standard does not address bags of sterile dialysis fluid or sorbent dialysis
fluid regeneration systems that regenerate and recirculate small volumes of the dialysis fluid.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 11663, Quality of dialysis fluid for haemodialysis and related therapies
ISO 13959, Water for haemodialysis and related therapies
ISO 14971, Medical devices — Application of risk management to medical devices
IEC 60601-1, Medical electrical equipment — Part 1: General requirements for basic safety and essential
performance
IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use —
Part 1: General requirements
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO 13958:2014(E)
3.1
acetate concentrate
concentrated solution of salts containing acetate, which, when diluted with dialysis water, yields
bicarbonate-free dialysis fluid for use in dialysis
Note 1 to entry: Acetate concentrate may contain glucose.
Note 2 to entry: Sodium acetate is used to provide a buffer in place of sodium bicarbonate.
Note 3 to entry: Acetate concentrate is used as a single concentrate.
3.2
acid concentrate
A-concentrate
acidified concentrated mixture of salts that, when diluted with dialysis water and bicarbonate
concentrate, yields dialysis fluid for use in dialysis
Note 1 to entry: The term “acid” refers to the small amount of acid (for example, acetic acid or citric acid) that is
included in the concentrate.
Note 2 to entry: Acid concentrate may contain glucose.
Note 3 to entry: Acid concentrate may be in the form of a liquid, a dry powder, other highly concentrated media,
or some combination of these forms.
3.3
action level
concentration of a contaminant at which steps should be taken to interrupt the trend toward higher,
unacceptable levels
3.4
additive
spike
small amount of a single chemical that, when added to the concentrate, will increase the concentration
of a single existing chemical by a value labelled on the additive packaging
3.5
batch system
apparatus in which the dialysis fluid is prepared in bulk before each dialysis session
3.6
bicarbonate concentrate
B-concentrate
concentrated preparation of sodium bicarbonate that, when diluted with dialysis water and acid
concentrate, makes dialysis fluid used for dialysis
Note 1 to entry: Sodium bicarbonate is also known as sodium hydrogen carbonate.
Note 2 to entry: Some bicarbonate concentrates also contain sodium chloride.
Note 3 to entry: Bicarbonate concentrate may be in the form of a liquid or a dry powder.
Note 4 to entry: Dry sodium bicarbonate, without added sodium chloride, is also used in concentrate generators
to produce a concentrated solution of sodium bicarbonate used by the dialysis machine to make dialysis fluid.
3.7
bicarbonate dialysis fluid
dialysis fluid containing physiological or higher concentrations of bicarbonate
Note 1 to entry: Bicarbonate dialysis fluid is generally produced from two concentrates: one containing bicarbonate
and the other containing acid and other electrolytes. See acid concentrate (3.2) and bicarbonate concentrate (3.6).
2 © ISO 2014 – All rights reserved

ISO 13958:2014(E)
3.8
biofilm
microbially derived sessile community characterized by cells that are irreversibly attached to a
substratum or interface or to each other, are imbedded in a matrix of extracellular polymeric substances
that they have produced, and exhibit an altered phenotype with respect to growth rate and gene
transcription
Note 1 to entry: The matrix, a slimy material secreted by the cells, protects the bacteria from antibiotics and
chemical disinfectants.
Note 2 to entry: A certain amount of biofilm formation is considered unavoidable in dialysis water systems. When
the level of biofilm is such that the action levels for microorganisms and endotoxins in the dialysis water cannot
be routinely achieved, the operation of the system is compromised from a medical and technical point of view.
This level of biofilm formation is often referred to as biofouling.
3.9
bulk delivery
delivery of large containers of concentrate to a dialysis facility
Note 1 to entry: Bulk delivery includes containers such as drums, which can be pumped into a storage tank
maintained at the user’s facility. Alternatively, the drums can be left at the facility and used to fill transfer
containers to transfer the concentrate to the dialysis machines. Bulk delivery can also include large containers
for direct connection to a central concentrate supply system.
Note 2 to entry: Bulk delivery also includes dry powder concentrates intended to be used with an appropriate
concentrate mixer.
3.10
central concentrate system
system that prepares and/or stores concentrate at a central point for subsequent distribution to its
points of use
3.11
central dialysis fluid delivery system
system that produces dialysis fluid from dialysis water and concentrate or powder at a central point and
distributes the dialysis fluid from the central point to individual dialysis machines
3.12
concentrate generator
system where the concentrate is delivered to the user as a powder in a container, suitable for attachment
to the dialysis machine with which it is intended to be used, and then the powder is converted into a
concentrated solution by the dialysis machine
Note 1 to entry: The solution produced by the concentrate generator is used by the dialysis machine to make the
final dialysis fluid delivered to the dialyser.
3.13
concentrate mixer
mixer for preparation of dialysis concentrate or dialysis fluid at a dialysis facility
3.14
device
individual water purification unit, such as a softener, carbon bed, reverse osmosis unit, or deionizer
Note 1 to entry: This term is synonymous with the term “component” as used by the US Food and Drug
[15]
Administration (see Reference ).
ISO 13958:2014(E)
3.15
dialysis fluid
dialysate
dialysis solution
aqueous fluid containing electrolytes and, usually, buffer and glucose, which is intended to exchange
solutes with blood during haemodialysis
Note 1 to entry: The term “dialysis fluid” is used throughout this International Standard to mean the fluid made
from dialysis water and concentrates that is delivered to the dialyser by the dialysis fluid delivery system. Such
phrases as “dialysate” or “dialysis solution” are used in place of dialysis fluid in some countries; however, that
usage is discouraged to avoid confusion.
Note 2 to entry: The dialysis fluid entering the dialyser is referred to as “fresh dialysis fluid”, while the fluid
leaving the dialyser is referred to as “spent dialysis fluid.”
Note 3 to entry: Dialysis fluid does not include prepackaged parenteral fluids used in some renal replacement
therapies, such as haemodiafiltration and haemofiltration.
3.16
dialysis fluid delivery system
device that: prepares dialysis fluid online from dialysis water and concentrates or that stores and
distributes premixed dialysis fluid; circulates the dialysis fluid through the dialyser; monitors the
dialysis fluid for temperature, conductivity (or equivalent), pressure, flow and blood leaks; and, prevents
dialysis during disinfection or cleaning modes
Note 1 to entry: The term includes reservoirs, conduits, proportioning devices for the dialysis fluid, and monitors
and associated alarms and controls assembled as a system for the purposes listed above.
Note 2 to entry: The dialysis fluid delivery system can be an integral part of a single-patient dialysis machine or a
centralized preparation system which feeds multiple bedside monitoring systems.
Note 3 to entry: Dialysis fluid delivery systems are also known as proportioning systems and dialysis fluid supply
systems.
3.17
dialysis water
water that has been treated to meet the requirements of ISO 13959 and which is suitable for use in
haemodialysis applications, including the preparation of dialysis fluid, reprocessing of dialysers,
preparation of concentrates, and preparation of substitution fluid for online convective therapies
3.18
disinfection
destruction of pathogenic and other kinds of microorganisms by thermal or chemical means
Note 1 to entry: Disinfection is a less lethal process than sterilization because it destroys most recognized
pathogenic microorganisms but does not necessarily destroy all microbial forms.
3.19
endotoxin
major component of the outer cell wall of gram-negative bacteria
Note 1 to entry: Endotoxins are lipopolysaccharides, which consist of a polysaccharide chain covalently bound
to lipid A. Endotoxins can acutely activate both humoral and cellular host defences, leading to a syndrome
characterized by fever, shaking, chills, hypotension, multiple organ failure, and even death if allowed to enter the
circulation in a sufficient dose. [See also pyrogen (3.30).]
3.20
endotoxin units
EU
units assayed by the Limulus amoebocyte lysate (LAL) test when testing for endotoxins
Note 1 to entry: Because activity of endotoxins depends on the bacteria from which they are derived, their activity
is referred to a standard endotoxin.
4 © ISO 2014 – All rights reserved

ISO 13958:2014(E)
Note 2 to entry: In some countries, endotoxin concentrations are expressed in international units (IU). Since the
harmonization of endotoxin assays, EU and IU are equivalent.
3.21
germicide
agent that kills microorganisms
3.22
haemodiafiltration
form of renal replacement therapy in which waste solutes are removed from blood by a combination of
diffusion and convection through a high-flux membrane
Note 1 to entry: Diffusive solute removal is achieved using a dialysis fluid stream as in haemodialysis. Convective
solute removal is achieved by adding ultrafiltration in excess of that needed to obtain the desired weight loss;
fluid balance is maintained by infusing replacement solution into the blood either before the dialyser (predilution
haemodiafiltration) after the dialyser (postdilution haemodiafiltration), or a combination of the two (mixed
dilution haemodiafiltration).
3.23
haemodialysis
form of renal replacement therapy in which waste solutes are removed primarily by diffusion from
blood flowing on one side of a membrane into dialysis fluid flowing on the other side
Note 1 to entry: Fluid removal that is sufficient to obtain the desired weight loss is achieved by establishing a
hydrostatic pressure gradient across the membrane. This fluid removal provides some additional waste solute
removal, particularly for solutes with higher molecular weight.
3.24
haemofiltration
form of renal replacement therapy in which waste solutes are removed from blood by convection
Note 1 to entry: Convective transport is achieved by ultrafiltration through a high-flux membrane. Fluid balance
is maintained by infusing a replacement solution into the blood either before the haemofilter (predilution
haemofiltration), after the haemofilter (postdilution haemofiltration) or a combination of the two (mixed dilution
haemofiltration).
Note 2 to entry: There is no dialysis fluid stream in haemofiltration.
3.25
Limulus amebocyte lysate test
LAL test
assay used to detect endotoxin
Note 1 to entry: The detection method uses the chemical response of an extract from blood cells of a horseshoe
crab (Limulus polyphemus) to endotoxins.
Note 2 to entry: Amebocyte lysate from a second horseshoe crab, Tachypleus tridentatus, may also be used to
detect endotoxin.
3.26
manufacturer
entity that designs, manufactures, fabricates, assembles, or processes a finished device
Note 1 to entry: Manufacturers include, but are not limited to, those who perform the functions of contract
sterilization, installation, relabelling, remanufacturing, repacking, or specification development, and initial
distributions of foreign entities performing these functions. The term does not cover preparation of concentrates
from prepackaged dry chemicals at a dialysis facility or the handling of bulk concentrates at a dialysis facility
after responsibility for the concentrate is transferred from the manufacturer to the user.
ISO 13958:2014(E)
3.27
microbiological contamination
contamination with any form of microorganism (e.g. bacteria, yeast, fungi, and algae) or with the by-
products of living or dead organisms such as endotoxins, exotoxins, and cyanobacterial toxins (derived
from blue-green algae)
3.28
nonpyrogenic
not eliciting a pyrogen reaction
Note 1 to entry: Historically, the threshold pyrogenic dose of 5 EU/kg/h (the minimum dose that produces fever)
has been used to set endotoxin limits of devices and injectable medications.
Note 2 to entry: The volume of fluid administered should not exceed the volume that would result in a total dose
of endotoxin of ≥5 EU/kg/h.
Note 3 to entry: This definition is applicable for fluids produced by online techniques, e.g. substitution and
priming fluids.
Note 4 to entry: The commonly used gel clot method has a sensitivity limit of 0,03 EU/ml.
3.29
proportioning system
apparatus that proportions dialysis water and haemodialysis concentrate to prepare dialysis fluid
3.30
pyrogen
fever-producing substance
Note 1 to entry: Pyrogens are most often lipopolysaccharides of gram-negative bacterial origin [see also endotoxin
(3.19)].
3.31
sodium hypochorite
chemical used for disinfection of haemodialysis systems
Note 1 to entry: Commercially available solutions of sodium hypochlorite are known in different countries by
terms such as bleach and javel. These solutions are used for disinfection at concentrations recommended by
equipment manufacturers.
3.32
sterile
free from viable microorganisms
Note 1 to entry: “Sterile” can be used to describe a packaged solution that was prepared using a terminal
sterilization process validated according to the methods of the applicable pharmacopoeia. A terminal sterilization
−6
process is commonly defined as one that achieves a sterility assurance level (SAL) of 10 , i.e. assurance of less
than one chance in a million that viable microorganisms are present in the sterilized article.
Note 2 to entry: Alternatively, “sterile” can be used to describe a solution prepared for immediate use by a
continuous process, such as filtration, that has been validated according to the methods of the applicable
pharmacopoeia to produce a solution free from microorganisms for the validated life of the filter.
3.33
storage tank
tank at the user’s facility for storage of dialysis water or concentrate from bulk deliveries, or for
concentrate prepared in bulk at the user’s facility from powder and dialysis water
6 © ISO 2014 – All rights reserved

ISO 13958:2014(E)
3.34
substitution fluid
fluid used in haemofiltration and haemodiafiltration treatments which is infused directly into the
patient’s blood as a replacement for the fluid that is removed from the blood by filtration
Note 1 to entry: Substitution fluid is also referred to as substitution solution or replacement solution.
Note 2 to entry: Substitution fluid may also be used for bolus administration, for priming of an extracorporeal
blood circuit, and for returning blood to the patient at the end of a treatment.
3.35
user
physician or physician’s representative or healthcare professional with a responsibility for the
prescription, production, and delivery of dialysis fluid
4 Requirements
4.1 Concentrates
4.1.1 Physical state
The concentrate for haemodialysis may be supplied in dry or aqueous form. Packaging may be for direct
use with a single dialysis machine or for use in systems supplying multiple dialysis machines (bulk use).
4.1.2 Solute concentrations
4.1.2.1 Liquid solute concentrations
All electrolytes identified on the label shall be present within ±5 % or ±0,1 mEq/l (expressed as dialysis
fluid concentrations), whichever is greater, of the stated concentration, with the exception of sodium,
which shall be present within ±2,5 % of the labelled concentration, or shall be present according to
approved specifications by the local regulations. If used, glucose shall be present within ±5 % or ±0,05 g/l
(when measured as properly diluted dialysis fluid), whichever is greater, of the labelled concentration,
or shall be present according to approved specifications by the local regulations. Where concentrates
include non-traditional constituents, such as antioxidants and iron compounds, these constituents shall
be present at nominal concentrations with ±5 % tolerances, or shall be present according to approved
specifications by the local regulations. If alternate, locally approved tolerances are used, the tolerances
shall be similarly stated and the rationale for their use documented.
Most concentrates are manufactured with standard traditional chemicals such as sodium chloride,
potassium chloride, magnesium chloride, calcium chloride, acetic acid, glucose, etc. New concentrates
are available in which certain chemicals have been substituted by others; for example, citric acid has
been substituted for acetic acid. Where this occurs, the labelling shall correctly reflect this and the
substitute chemicals shall be present at nominal concentrations with ±5 % tolerances, or shall be present
according to approved specifications by the local regulations. If alternate, locally approved tolerances
are used, the tolerances shall be similarly stated and the rationale for their use documented.
4.1.2.2 Solute concentrations from powder
When concentrate is packaged in dry form or a combination of dry and liquid and is mixed according
to the manufacturer’s instruction for use, the final concentrate shall meet the requirements of 4.1.2.1.
4.1.3 Water
The quality of water used in the manufacture of the concentrate shall be in accordance with ISO 13959.
ISO 13958:2014(E)
4.1.4 Bacteriology of concentrates
4.1.4.1 Bacteriology of bicarbonate concentrates
Concentrate containing bicarbonate supplied as a liquid shall be provided in a sealed container and
manufactured by a process validated to produce dialysis fluid meeting the microbiological requirements
of ISO 11663, when used according to the manufacturer’s instructions. Bicarbonate powder intended for
the preparation of concentrate at a dialysis facility shall be capable of producing dialysis fluid meeting
the microbiological requirements of ISO 11663, when used according to the manufacturer’s instructions.
4.1.4.2 Bacteriology of acid concentrates
There are no published reports of acid concentrate supporting bacterial growth and as such, acid
concentrate need not be tested for bacterial growth.
4.1.5 Endotoxin levels
The concentrate shall be formulated and packaged using a process validated to produce dialysis fluid
meeting the endotoxin requirements of ISO 11663 or the applicable pharmacopoeia when used according
to the manufacturer’s instructions.
4.1.6 Fill quantity
The excess fill volume of liquid containers and the excess fill weight of powder containers used with
batch systems for a single dialysis treatment shall be within 2 % of the labelled volume or weight. The
fill weight of bulk delivered powdered concentrate shall be such that, when mixed according to the
manufacturer’s instructions, it produces liquid concentrate that meets the requirements of 4.1.2.1. The
fill weight of a concentrate generator shall be such that the device performs as intended. For all other
applications, the fill volume or weight shall be ≥100 % of the stated volume or weight.
4.1.7 Chemical grade
All chemicals shall meet the requirements of the applicable pharmacopoeia, including all applicable
portions of the general notices and of the general requirements for tests and assay. If all other requirements
are met, monograph limits for sodium, potassium, calcium, magnesium, and/or pH may be exceeded
provided that correction is made, if necessary, for the presence of those ions in the final formulation.
Also, any pharmacopoeia requirements that the chemicals be labelled for use in haemodialysis need
not be complied with if the manufacturer is performing its own testing to meet the requirements of the
applicable pharmacopoeia.
4.1.8 Particulates
The aqueous dialysis concentrate shall be filtered through a nominal 1 µm or finer particulate filter.
The particulate filter used shall have a non-fibre-releasing membrane that does not contain material of
known potential for human injury.
4.1.9 Additives — “Spikes”
If additives are supplied, the concentration, when properly diluted with water or concentrate, shall yield
values within ±5 % by weight of the labelled value.
4.1.10 Containers
Containers, including the closures, shall not interact chemically or physically with the contents to alter
the strength, purity, or quality of the concentrate during handling, storage, and shipment. The containers
shall have closures that prevent contamination or loss of content. Each container shall be marked to
indicate its contents. One means of indicating the contents is to use an appropriate symbol (see Table 2).
8 © ISO 2014 – All rights reserved

ISO 13958:2014(E)
4.1.11 Bulk-delivered concentrate
When concentrate is delivered in bulk form, the responsibility for ensuring compliance with this
International Standard shall pass from the manufacturer to the user at the legal point of transfer of
the shipment. Once the concentrate is transferred from the manufacturer to the user, it becomes the
user’s responsibility to maintain the product in a usable state with appropriate labels and non-tamper
procedures.
4.1.12 Concentrate generators
Concentrate generator systems include systems that mix p
...