ISO 22519:2023

INTERNATIONAL ISO
STANDARD 22519
Second edition
2023-04
Membrane-based generation of water
for injection (WFI)
Production d'eau pour préparations injectables (EPPI) utilisant des
membranes
Reference number
© ISO 2023
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ii
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms, definitions and abbreviated terms . 1
3.1 Terms and definitions . 1
3.2 Abbreviated terms . 2
4 System boundaries .3
5 Feed water. 3
6 Process design for membrane-based WFI generation systems .3
6.1 General . 3
6.2 Design conditions . 4
6.3 Important design factors . . 4
6.4 Examples of possible configurations of water technology stages in WFI generation
systems . 4
6.5 Primary microbial reduction unit operations . 4
6.6 Instrumentation . 5
7 Sanitization . .5
7.1 General . 5
7.2 Sanitization types . 5
8 Construction . 6
9 Demonstrating performance of critical quality attributes . 6
10 Sampling . 6
11 System operation . 7
12 System maintenance .7
13 Control . 7
14 Other considerations . 8
Bibliography . 9
iii
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
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www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 282, Water reuse.
This second edition cancels and replaces the first edition (ISO 22519:2019), which has been technically
revised.
The main changes are as follows:
— title changed;
— PW systems removed from the Scope;
— document structure revised.
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
Introduction
The water quality specifications for water for injection (WFI) are given in national and International
Standards and are well defined and understood.
The WFI generation systems potentially have to be able to cope with fluctuating feed water quality and
be in accordance with the company policy and current good manufacturing practice (cGMP).
Properly engineered, constructed, operated and maintained membrane-based generation systems
can have comparable reliability in meeting WFI quality specifications with low operational costs in
comparison with thermal-based WFI generation. At the time of publication, all major pharmacopoeia
allow non-distillation-based WFI generation, with the exception of the Chinese Pharmacopoeia. The
Chinese Pharmacopoeia has initiated revisions to related standards.
This document has been developed to address the lack of an International Standard concerning
membrane-based WFI generation.
The aim of this document is to:
— set out clear principles needed for reliable membrane-based generation of WFI;
— improve membrane-based generation of WFI process systems and methods;
— combine relevant standards, guidelines and global expert knowledge into one International
Standard;
— consider in-system microbiological aspects of WFI generation;
— standardize expectations for membrane-based WFI generation.
This document provides a global benchmark that can be used by industries that use the WFI generation
system.
v
INTERNATIONAL STANDARD ISO 22519:2023(E)
Membrane-based generation of water for injection (WFI)
1 Scope
This document provides a benchmark for evaluation of the design, operation and performance of water
for injection (WFI) generation systems based on membranes.
This document is applicable to the design of new systems.
This document covers the following topics:
— principles of membrane-based WFI generation systems;
— process design, construction, operation and maintenance of membrane-based WFI generation
systems;
— controlling membrane-based WFI generation system parameters.
This document does not cover the following topics:
— validation;
— distillation.
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 20670, Water reuse — Vocabulary
3 Terms, definitions and abbreviated terms
For the purposes of this document, the terms and definitions given in ISO 20670 and the following apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1 Terms and definitions
3.1.1
pretreatment
equipment and process stages up to and including the first-pass reverse osmosis (RO) pump or other
membrane-based primary bioburden reduction step
3.1.2
generation system
equipment and process stages after (downstream) reverse osmosis (RO) stage 1 pump
3.1.3
multimedia filter
MMF
layered filtration media in a pressurized container, used to reduce the level of suspended solids in
incoming feed water
Note 1 to entry: Media layers can consist of anthracite, sand and garnet.
3.1.4
chlorination
dosage or generation of hypochlorite or chlorine to generate controlled free chlorine levels in the
system
3.1.5
activated carbon filter
ACF
activated carbon media for removal of free chlorine, chloramines and total organic carbon (TOC)
Note 1 to entry: The media can be applied as a granular activated carbon (GAC) pressurized container or a
cartridge type. The configuration of the activated carbon filter can depend on, for example, the level of feed
water impurities and system capacity.
3.1.6
ultraviolet
UV
irradiation of water with light in wavelengths ranging from 180 nm to 350 nm for dechlorination
or disinfection purposes at higher wavelengths and total organic carbon (TOC) reduction at lower
wavelengths
3.1.7
molecular weight cut-off
MWCO
molecular weight at which 90 % of the macromolecular solute is rejected by the membrane
3.1.8
electrodeionization
EDI
process for ion removal from water utilizing electricity, ion exchange membranes and resin
3.1.9
continuous electrodeionization
CEDI
process for ion removal from water utilizing electricity, ion exchange membranes and resin
3.1.10
polishing UF
polishing ultrafiltration
membrane-based process for reduction of endotoxin, total organic carbon (TOC) and bacteria post-RO
or post-electrodeionization (EDI) or continuous electrodeionization (CEDI)
3.2 Abbreviated terms
ACF activated carbon filter
CEDI continuous electrodeionization
EDI electrodeionization
EPDM ethylene propylene diene (M-group)
HWS hot water sanitization
MWCO molecular weight cut-off
MMF multimedia filter
PTFE polytetrafluoroethylene
RO reverse osmosis
SOP standard operating procedure
SS stainless steel
TOC total organic carbon
UF ultrafiltration
UV ultraviolet
WFI water for injection
4 System boundaries
For the purpose of this document, the boundaries for the WFI generation system are as follows:
a) The inlet of potable water to the equi
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