Purified water and water for injection pretreatment and production systems

This document specifies design, materials selection, construction and operation of Purified Water (PW) and Water for Injection (WFI) pretreatment and membrane-based production systems. As many different types of feed water are possible, different components and configurations are presented. A decision matrix is provided to give guidance for the different types of feed water. This document excludes — selection of the appropriate compendial water definition per system: e.g. PW, WFI or other; — thermal process for generation of PW/WFI; — loops, storage and distribution; — pure steam generation and distribution; — laboratory water systems and — validation.

Systèmes de prétraitement et de production d'eau purifiée et d'eau d'injection

General Information

Status
Published
Publication Date
28-May-2019
Current Stage
9092 - International Standard to be revised
Start Date
07-Jan-2020
Completion Date
07-Jan-2020
Ref Project

Buy Standard

Standard
ISO 22519:2019 - Purified water and water for injection pretreatment and production systems
English language
35 pages
sale 15% off
Preview
sale 15% off
Preview

Standards Content (sample)

INTERNATIONAL ISO
STANDARD 22519
First edition
2019-06
Purified water and water for injection
pretreatment and production systems
Systèmes de prétraitement et de production d'eau purifiée et d'eau
d'injection
Reference number
ISO 22519:2019(E)
ISO 2019
---------------------- Page: 1 ----------------------
ISO 22519:2019(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: 2 ----------------------
ISO 22519:2019(E)
Contents Page

Foreword ..........................................................................................................................................................................................................................................v

Introduction ................................................................................................................................................................................................................................vi

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

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

3 Terms, definitions and abbreviated terms ................................................................................................................................1

3.1 Terms and definitions ....................................................................................................................................................................... 1

3.2 Abbreviated terms ............................................................................................................................................................................... 3

4 Design and practices .........................................................................................................................................................................................6

4.1 Setting system boundaries............................................................................................................................................................ 6

4.2 General system requirements .................................................................................................................................................... 6

4.3 User Requirements Specifications (URS) scope ......................................................................................................... 7

4.4 Detailed system capacity calculation ................................................................................................................................... 8

5 Selecting materials, methods and system components ...............................................................................................8

5.1 Recommended system components/treatment stages ....................................................................................... 8

5.2 Advantages and disadvantages of system components/treatment stages ......................................10

5.3 Materials of construction — General ................................................................................................................................14

5.4 Stainless steel (SS) piping — General ..............................................................................................................................15

5.5 Non-final product water piping/tubing in the PW/WFI pretreatment and production ......15

5.6 Piping/tubing in contact with PW/WFI product ....................................................................................................16

6 Sampling .....................................................................................................................................................................................................................16

6.1 Sampling principles .........................................................................................................................................................................16

6.2 Minimum sampling point and locations ........................................................................................................................17

6.3 Sampling conductivity ...................................................................................................................................................................17

7 Instruments ............................................................................................................................................................................................................17

7.1 Minimum instrumentation for installation .................................................................................................................17

7.2 Parameters for measuring, alarming, storing and graphing from online instruments .........18

8 System design .......................................................................................................................................................................................................19

8.1 Specification of feed water .........................................................................................................................................................19

8.2 System selection table based on feed water quality ............................................................................................19

9 Operation ..................................................................................................................................................................................................................19

9.1 Production ...............................................................................................................................................................................................19

9.2 Recirculation when storage tank full ................................................................................................................................19

9.3 Sanitization .............................................................................................................................................................................................19

9.4 Chlorine and chlorination...........................................................................................................................................................20

10 Maintenance ...........................................................................................................................................................................................................20

10.1 Standard Operating Procedure (SOP´s) ..........................................................................................................................20

10.2 Filter replacement .............................................................................................................................................................................21

10.3 Chlorine instrumentation ...........................................................................................................................................................21

10.4 Carbon dioxide .....................................................................................................................................................................................21

10.5 Membrane Integrity for polishing UF ...............................................................................................................................21

11 Specific Good Manufacturing Practice (GMP) requirements ...............................................................................22

11.1 General ........................................................................................................................................................................................................22

11.2 Safety considerations .....................................................................................................................................................................22

11.3 Commissioning and qualification requirements ....................................................................................................22

12 Control philosophy ..........................................................................................................................................................................................23

12.1 Minimum control loops needed for installation......................................................................................................23

12.2 Automation ..............................................................................................................................................................................................23

13 Alarms ..........................................................................................................................................................................................................................23

13.1 Required alarms ..................................................................................................................................................................................23

© ISO 2019 – All rights reserved iii
---------------------- Page: 3 ----------------------
ISO 22519:2019(E)

13.2 Recommended alarms ...................................................................................................................................................................23

14 Recommended engineering documentation ........................................................................................................................24

14.1 General user guide ............................................................................................................................................................................24

14.2 Instrumentation documentation ..........................................................................................................................................24

14.3 General piping/tubing ...................................................................................................................................................................24

14.4 PW/WFI product piping/tubing ...........................................................................................................................................24

14.5 Tanks .............................................................................................................................................................................................................25

14.6 Pumps ..........................................................................................................................................................................................................25

14.7 Insulation ..................................................................................................................................................................................................25

14.8 Signs ..............................................................................................................................................................................................................25

14.9 Software .....................................................................................................................................................................................................25

14.10 Electrical documentation ............................................................................................................................................................26

14.11 Factory acceptance test (FAT) protocol ..........................................................................................................................26

14.12 IQ/OQ protocol ....................................................................................................................................................................................26

14.13 Spare parts list .....................................................................................................................................................................................26

Annex A (informative) Examples of PW production systems ...................................................................................................27

Annex B (informative) Examples of feed water categories .........................................................................................................30

Annex C (informative) System selection table .........................................................................................................................................31

Annex D (informative) Configuration of typical integrity test for polishing UF ...................................................34

Bibliography .............................................................................................................................................................................................................................35

iv © ISO 2019 – All rights reserved
---------------------- Page: 4 ----------------------
ISO 22519:2019(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 282, Water reuse.

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.
© ISO 2019 – All rights reserved v
---------------------- Page: 5 ----------------------
ISO 22519:2019(E)
Introduction

A large variety of water systems exists today in the Biopharma market; often these water systems

are of differing levels of efficiency and have different maintenance needs. Water quality for Purified

Water (PW) and Water for Injection (WFI) is specified in national and international standards, but a

standardized system for producing PW and WFI is not in place.

This document provides a standard benchmark that can be used by the industries that use PW and/or

WFI, national governments, state authorities and regulatory bodies to evaluate PW/WFI systems.

This document

— allows users to specify water systems that fit specific needs without being experts in the water

system field;

— allows users to decide whether the offered systems are safe, efficient and sustainable;

— enables national governments, state authorities and regulatory bodies to perform professional audits;

— provides auditors a standard check list to harmonize equipment and systems in the water industry;

— sets a high benchmark for suppliers of water systems all over the world, to be used as a point of

reference for their systems and;

— will improve reliability of the water generation process methods and water product while reducing

downtime needed for scheduled and non-scheduled maintenance.
This document also defines technical terms related to PW and WFI generation.
See Annex A, "examples of PW production systems".
See Annex B, "examples of feed water categories".
See Annex C, "system selection table".
See Annex D, "configuration of typical integrity test for polishing UF".
vi © ISO 2019 – All rights reserved
---------------------- Page: 6 ----------------------
INTERNATIONAL STANDARD ISO 22519:2019(E)
Purified water and water for injection pretreatment and
production systems
1 Scope

This document specifies design, materials selection, construction and operation of Purified Water (PW)

and Water for Injection (WFI) pretreatment and membrane-based production systems.

As many different types of feed water are possible, different components and configurations are

presented. A decision matrix is provided to give guidance for the different types of feed water.

This document excludes

— selection of the appropriate compendial water definition per system: e.g. PW, WFI or other;

— thermal process for generation of PW/WFI;
— loops, storage and distribution;
— pure steam generation and distribution;
— laboratory water systems and
— validation.
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 following terms and definitions given in ISO 20670 and the

following 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/
3.1 Terms and definitions
3.1.1
pretreatment
equipment and process stages before (upstream) high pressure RO pump
3.1.2
production system
equipment and process stages after (downstream) high pressure RO pump

Note 1 to entry: If there is a tank, before the high pressure RO pump, then the tank can be included in the

production system.
© ISO 2019 – All rights reserved 1
---------------------- Page: 7 ----------------------
ISO 22519:2019(E)
3.1.3
pretreatment ultra filtration
pretreatment UF

membrane based process for removal of suspended solids, bacteria and TOC upstream of RO

Note 1 to entry: Usually operated with a reject stream and cleaned with a back wash.

3.1.4
MMF
multi media filter

layered filtration media in a pressurized container, used to reduce the level of suspended solids

(turbidity) in incoming feed water
Note 1 to entry: Media layers can consist of anthracite, sand and garnet.
3.1.5
flushed screen/disc filter
FS/DF

filter based on a static screen with a water flush of the cake that builds up on the screen

3.1.6
chlorination

dosage/generation of Hypochlorite/Chlorine to generate controlled free chlorine levels in the system

3.1.7
softener

pressurized container of softening resin for replacement of hardness ions, calcium, magnesium, barium

and strontium, with the sodium ion
3.1.8
antiscalant

chemical scale inhibitor or sequestering agent that minimize the potential for scale precipitation on the

reject surface of a RO membrane
3.1.9
electric scale control
ESC

electrolytic scale inhibitor that minimizes the potential for scale precipitation on the reject surface of a

RO membrane
3.1.10
activated carbon filter
ACF

granular activated carbon (GAC) pressurized container of activated carbon media for removal of free

chlorine, chloramines and Total Organic Carbon (TOC)
3.1.11
degassing CO contact membrane
degasser

microporous hollow fiber membrane that brings into direct contact a liquid and strip gas and/or vacuum

Note 1 to entry: The dissolved gas in the liquid will pass though the membrane and into the strip gas and/or

vacuum on the other side of the membrane.
3.1.12
ultra violet (UV) lamp
irradiation of water with UV light in wavelengths ranging from 180 nm to 350 nm
2 © ISO 2019 – All rights reserved
---------------------- Page: 8 ----------------------
ISO 22519:2019(E)
3.1.13
microfiltration

pressure driven separation process designed to remove particles and macromolecules. MF is usually

installed as part of the pre-treatment for other downstream process
Note 1 to entry: The nominal filtration sizes are 0,05 micron to 2 micron.
3.1.14
single pass reverse osmosis
SPRO

single pass membrane based process to separate dissolved ions and suspended solids

3.1.15
double pass reverse osmosis
DPRO

double pass membrane-based process to separate dissolved ions and suspended solids

3.1.16
continuous electro de-ionization
CDI/EDI/CEDI

process for ion removal from water utilizing: electricity, ion exchange membranes and resin

3.1.17
polishing ultra filtration
polishing UF

membrane based process using molecular weight cut off 6 000 or smaller for reduction of endotoxin,

TOC and bacteria post RO or post CDI/EDI/CEDI
3.1.18
anion and cation de-ionizers

separate pressurized containers of anion ion exchange resin and cation ion exchange resin, for removal

of both cations and anions
Note 1 to entry: Resins are regenerated on site or off site.
3.1.19
single use mixed bed polisher

pressurized containers of mixed anion and cation ion exchange resin for removal of both cations

and anions
Note 1 to entry: Resins are regenerated off site.
3.2 Abbreviated terms
ACF activated carbon filter
AS antiscalant
BW butt welding
CD chlorine dioxide
CFU colony forming units
CIP cleaning in place
CIT conductivity indicator and transmitter
CLIT chlorine indicator and transmitter
© ISO 2019 – All rights reserved 3
---------------------- Page: 9 ----------------------
ISO 22519:2019(E)
DPRO double pass RO
EP European Pharmacopeia
EPDM ethylene propylene diene monomer
ESC electric scale control
FAT factory acceptance test
FIT flow indicator and transmitter
FRP/PE fibre reinforced plastic (on) polyethylene
FS/DF filter screen/disk filter
GAC granular activated carbon
GMP good manufacturing practice
HOD hydro optical dechlorination
HP high pressure
HSDS Human Services Data Specification
HWS hot water sanitization
ID inside diameter
IQ Installation Qualification
ISPE International Society for Pharmaceutical Engineering
JP Japanese Pharmacopeia
L/D ratio between piping/tubing length/diameter
LT level transmitter
MF microfiltration
MMF multimedia filter
MP mechanical polish
NA non applicable
NaOH sodium hydroxide
NFPA National Fire Protection Association
NR not recommended
OSHA Occupational Safety and Health Administration
ORP oxidation reduction potential
OQ Operational Qualification
P possible
4 © ISO 2019 – All rights reserved
---------------------- Page: 10 ----------------------
ISO 22519:2019(E)
PEEK polyether ether ketone
PFA perfluoralkoxy alkanes
PI pressure indicator
PIT pressure indicator and transmitter
POU point of use
PPP PW/WFI pretreatment and production
PQ Performance Qualification
PS pure steam
PTFE polytetrafluoroethylene
PVC polyvinyl chloride
PW Purified Water
QIT quantity indicator and transmitter
R recommended
RO reverse osmosis
SBS sodium bi sulfite
S&D Storage and Distribution
SOP standard operating procedure
SPRO single pass reverse osmosis (RO)
SS stainless steel
TC Tri Clamp
TDS total dissolved solids
TIG/GTAW Tungsten Inert Gas/Gas Tungsten Arc Welding
TT temperature indicator
TOC total organic carbon
UF ultrafiltration
URS User Requirements Specifications
USP US Pharmacopeia
WFI Water for Injection
© ISO 2019 – All rights reserved 5
---------------------- Page: 11 ----------------------
ISO 22519:2019(E)
4 Design and practices
4.1 Setting system boundaries

4.1.1 A PW/WFI Pretreatment and Production system starts at the valve (inclusive) before the first

supplied water filter component/MMF.

4.1.2 A PW/WFI Pretreatment and Production system end boundary is at the inlet valve (inclusive) of

the PW/WFI storage tank or at the POU if a tank is not installed.

4.1.3 The PW/WFI storage tank should not be included in the PW/WFI Pretreatment and Production.

4.1.4 “Industrial” treatment systems upstream to the PW/WFI Pretreatment and Production, including

supply to other plant utilities e.g. steam boilers, potable water usage, feed to cooling towers etc. should

not be included in the PW/WFI Pretreatment and Production.
4.2 General system requirements

4.2.1 A “build clean” concept shall be employed during the installation of PW/WFI Pretreatment and

Production systems: supply of piping/tubing and equipment in clean condition and installation methods

that prevent ingress of contaminants.

4.2.2 Incoming feed water shall meet local standards or WHO standards for potable water. If this is not

the case, additional systems shall be installed to improve the water feed parameters before the PW/WFI

Pretreatment and Production.

4.2.3 The PW/WFI Pretreatment and Production water quality shall show improvement in all quality

parameters as the water advances through the system.

4.2.4 The following parameters shall be steadily reduced at each stage in the system:

— microbial total count;
— conductivity and;
— TOC.

4.2.5 PW/WFI quality shall be according to the last revision of the local/national/relevant

Pharmacopoeia. Table 1 provides recommended water quality.
Table 1 — Recommended water quality
# Parameter RO feed After RO PW WFI
1 Hardness (PPM CaCO ) ≤ feed water < 1 < 1 < 1
2 TOC (ppb) ≤ feed water < 500 < 500 (online) < 500 (online)
3 Endotoxin (EU/ml) NA NA NA < 0,25
4 Microbial total count (cfu/ml) < 500 < 200 < 100 < 10 cfu/100 ml
5 Free Chlorine (ppm) < 0,05 < 0,05 < 0,05 < 0,05
6 Pseudomonas (cfu/100 ml) < 1 < 1 < 1 < 1
Conductivity shall be measured uncompensated at 25 °C according to USP.
6 © ISO 2019 – All rights reserved
---------------------- Page: 12 ----------------------
ISO 22519:2019(E)
Table 1 (continued)
# Parameter RO feed After RO PW WFI
7 E. coli (cfu/100 ml) < 1 < 1 < 1 < 1
8 Total coliforms, Fungus, (cfu/100 ml) < 1 < 1 < 1 < 1
9 Conductivity (µS/cm) Like feed water < 10 < 1,3 (online) < 1,3 (online)
Conductivity shall be measured uncompensated at 25 °C according to USP.

4.2.6 A sampling programme with acceptance criteria shall be in place to gather, analyse and document

this water quality improvement.

4.2.7 During production, the PW/WFI Pretreatment and Production shall control the maximum water

temperature in the system. During production, the maximum temperature of the warmest point in the

system shall be no more than 25 °C (guidance value).

4.2.8 All parts of the PW/WFI Pretreatment and Production shall be hot water sanitized, from the feed

water inlet valve to the PW/WFI fill valve. During sanitization, the PW/WFI Pretreatment and Production

shall control the water temperature in the system. During sanitization, the all the points of the system

should be at a minimum of 80 °C (guidance value).

4.2.9 The PW/WFI Pretreatment and Production system shall be designed, controlled, regulated,

operated and maintained to ensure that the final water quality reliably meets final water quality

standard set in 4.2.5. This performance shall be stable under all conditions including common worst-

case scenarios, changing seasons or other fluctuating environmental conditions.
4.3 User Requirements Specifications (URS) scope
The scope of the User Requirements Specifications shall include the following;
— selection of water compendial standard based on products supplied;
— specification of the final water standard parameters;
— safety and Good Manufacturing Practice requirements for the system;
— list of main components;
— preliminary sizing of production flow rate;
— number of production units;
— functional requirements;
— materials of construction;
— equipment surface finish;
— biological control concept;
— high level control: interlocks, alarms and warnings;
— documentation required (see Clause 14);
— validation as required by respective authorities and;
— Performance Qualification (PQ) monitor
...

Questions, Comments and Discussion

Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.