ISO/DIS 22441

Sterilization of health care products — Low temperature vaporized hydrogen peroxide — Requirements for the development, validation and routine control of a sterilization process for medical devices

Stérilisation des produits de santé — Vapeur de peroxyde d’hydrogène à basse température — Exigences pour la mise au point, la validation et le contrôle de routine d’un procédé de stérilisation pour dispositifs médicaux

Sterilizacija izdelkov za zdravstveno oskrbo - Sterilizatorji s paro z nizko temperaturo in z vodikovim peroksidom - Zahteve za razvoj, validacijo in rutinsko kontrolo sterilizacijskih postopkov za medicinske pripomočke

General Information

• Status: Published
• ICS: 11.080.01 - Sterilization and disinfection in general
• Technical Committee: ISO/TC 198 - Sterilization of health care products
• Drafting Committee: ISO/TC 198/WG 16 - Vaporized hydrogen peroxide sterilization
• Current Stage: 6000 - International Standard under publication
• Completion Date: 09-Jun-2022
• Ref Project: oSIST ISO/DIS 22441:2021 - Sterilization of health care products - Low temperature vaporized hydrogen peroxide -- Requirements for the development, validation and routine control of a sterilization process for medical devices

Standards Content (sample)

SLOVENSKI STANDARD
oSIST ISO/DIS 22441:2021
01-december-2021
Sterilizacija izdelkov za zdravstveno oskrbo - Sterilizatorji s paro z nizko

temperaturo in z vodikovim peroksidom - Zahteve za razvoj, validacijo in rutinsko

kontrolo sterilizacijskih postopkov za medicinske pripomočke

Sterilization of health care products - Low temperature vaporized hydrogen peroxide --

Requirements for the development, validation and routine control of a sterilization

process for medical devices
Stérilisation des produits de santé -- Vapeur de peroxyde d’hydrogène à basse

température -- Exigences pour la mise au point, la validation et le contrôle de routine

d’un procédé de stérilisation pour dispositifs médicaux
Ta slovenski standard je istoveten z: ISO/DIS 22441
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
oSIST ISO/DIS 22441:2021 en,fr,de

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

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oSIST ISO/DIS 22441:2021
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oSIST ISO/DIS 22441:2021
DRAFT INTERNATIONAL STANDARD
ISO/DIS 22441
ISO/TC 198 Secretariat: ANSI
Voting begins on: Voting terminates on:
2021-07-19 2021-10-11
Sterilization of health care products — Low temperature
vaporized hydrogen peroxide — Requirements for
the development, validation and routine control of a
sterilization process for medical devices

Stérilisation des produits de santé — Basse température à la vapeur de peroxyde d’hydrogène — Exigences

pour le développement, la validation et le contrôle de routine d'un procédé de stérilisation des dispositifs

médicaux
ICS: 11.080.01
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,
This document is circulated as received from the committee secretariat.
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
Reference number
NATIONAL REGULATIONS.
ISO/DIS 22441:2021(E)
RECIPIENTS OF THIS DRAFT ARE INVITED
TO SUBMIT, WITH THEIR COMMENTS,
NOTIFICATION OF ANY RELEVANT PATENT
RIGHTS OF WHICH THEY ARE AWARE AND TO
PROVIDE SUPPORTING DOCUMENTATION. ISO 2021
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oSIST ISO/DIS 22441:2021
ISO/DIS 22441:2021(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2021

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: [phone]
Email: [e-mail]
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved
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oSIST ISO/DIS 22441:2021
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Contents Page

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

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

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

1.1 Inclusions ..................................................................................................................................................................................................... 1

1.2 Exclusions .................................................................................................................................................................................................... 1

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

3 Terms and definitions ..................................................................................................................................................................................... 2

4 Quality management system elements ......................................................................................................................................11

5 Sterilizing agent characterization ...................................................................................................................................................11

5.1 General ........................................................................................................................................................................................................11

5.2 Sterilant ......................................................................................................................................................................................................12

5.3 Microbicidal effectiveness ..........................................................................................................................................................12

5.4 Effects on materials ......... .................................................................................................................................................................12

5.5 Safety and the environment ......................................................................................................................................................13

6 Process and equipment characterization ................................................................................................................................13

6.1 General ........................................................................................................................................................................................................13

6.2 Equipment characterization .....................................................................................................................................................14

7 Product definition ............................................................................................................................................................................................15

8 Process definition .............................................................................................................................................................................................16

9 Validation ..................................................................................................................................................................................................................18

9.1 General ........................................................................................................................................................................................................18

9.2 Installation qualification (IQ) ..................................................................................................................................................19

9.2.1 General...................................................................................................................................................................................19

9.2.2 Equipment ..........................................................................................................................................................................19

9.3 Operational qualification (OQ) ...............................................................................................................................................19

9.4 Performance qualification (PQ) .............................................................................................................................................20

9.5 Review and approval of validation .....................................................................................................................................21

10 Routine monitoring and control .......................................................................................................................................................22

11 Product release from sterilization ..................................................................................................................................................22

12 Maintaining process effectiveness ..................................................................................................................................................23

12.1 General ........................................................................................................................................................................................................23

12.2 Recalibration ..........................................................................................................................................................................................23

12.3 Maintenance of equipment ........................................................................................................................................................23

12.4 Requalification .....................................................................................................................................................................................23

12.5 Assessment of change ....................................................................................................................................................................24

Annex A (normative) Factors to be considered in selection of microorganisms for

demonstrating microbicidal effectiveness .............................................................................................................................25

Annex B (normative) Approach 1 — Process definition based on inactivation of the

microbial population in its natural state (bioburden method) ........................................................................27

Annex C (normative) Approach 2 — Process definition based on inactivation of reference

microorganisms and knowledge of bioburden (BI/bioburden method) ...............................................29

Annex D (normative) Approach 3 — Conservative process definition based on inactivation

of reference microorganisms (overkill method) .............................................................................................................31

Annex E (informative) Guidance on application of this document ....................................................................................34

Annex F (informative) Schematic example of a VH2O2 sterilization cycle ................................................................57

Annex G (informative) Environmental aspects .......................................................................................................................................58

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Annex H (informative) Justification for the number of temperature sensors and biological

indicators ..................................................................................................................................................................................................................63

Annex I (informative) Aspects of VH2O2 .......................................................................................................................................................65

Bibliography .............................................................................................................................................................................................................................69

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oSIST ISO/DIS 22441:2021
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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 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 198, Sterilization of health care products.

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.
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oSIST ISO/DIS 22441:2021
ISO/DIS 22441:2021(E)
Introduction

This document specifies the requirements for the development, validation and routine control of

sterilization processes using a vaporized composition of water and hydrogen peroxide (H O ) as the

2 2

sterilizing agent. Vaporized hydrogen peroxide (VH2O2) sterilizers process typically below 60°C and

are primarily used for the sterilization of thermolabile or moisture-sensitive medical devices in health

care facilities but can also be used for any reusable medical device that has been validated as compatible

with the VH2O2 process. The sterilizers operate automatically using pre-set cycles. They can also be

used during commercial production of medical devices.

NOTE Work is underway within CEN/TC 102 to develop a standard for requirements for VH2O2 sterilizers

(EN 17180, Sterilizers for medical purposes — Low temperature vaporized hydrogen peroxide sterilizers —

Requirements and testing). It is intended that applicable test procedures to demonstrate conformity (e.g. type

tests and works tests) will be primarily described in the draft of EN 17180.

A sterile medical device is one that is free of viable microorganisms. International Standards that

specify requirements for validation and routine control of sterilization processes require, when it

is necessary to supply a sterile medical device, that adventitious microbiological contamination of a

medical device prior to sterilization be minimized. Even so, medical devices produced under standard

manufacturing conditions in accordance with the requirements for quality management systems (see,

for example, ISO 13485) could, prior to sterilization, have microorganisms on them. Such medical

devices are non-sterile. The purpose of sterilization is to inactivate the microbiological contaminants

and thereby transform the non-sterile medical devices into sterile ones.

The kinetics of inactivation of microorganisms by physical or chemical agents used to sterilize

medical devices generally can best be described by an exponential relationship between the number of

microorganisms surviving and the extent of treatment with the sterilizing agent; inevitably this means

that there is always a finite probability that a microorganism might survive regardless of the extent of

treatment applied. For a given treatment, the probability of survival is determined by the number and

resistance of microorganisms and by the environment in which the organisms exist during treatment. It

follows that the sterility of any one medical device in a population subjected to sterilization processing

cannot be guaranteed and the sterility of a processed population is defined in terms of the probability

of there being a viable microorganism present on a medical device.

This document describes requirements that, if met, will provide a sterilization process by VH2O2 with

appropriate microbicidal activity intended to sterilize medical devices. Furthermore, conformance

with the requirements ensures that the sterilization process is both reliable and reproducible so that

predictions can be made, with reasonable confidence, that there is a small probability of there being a

viable microorganism present on a medical device after sterilization. Specification of this probability is

a matter for regulatory authorities and can vary from country to country (see, for example, EN 556-1

and ANSI/AAMI ST67).

Generic requirements of the quality management system for design and development, production,

installation and servicing are given in ISO 9001 and particular requirements for quality management

systems for medical device production are provided in national and international standards (e.g.

ISO 13485). The standards for quality management systems recognise that, for certain processes used

in manufacturing, the effectiveness of the process cannot be fully verified by subsequent inspection

and testing of the product. Sterilization is an example of such a process. For this reason, sterilization

processes are validated for use, the performance of the sterilization process is monitored routinely and

the equipment is maintained.

Exposure to a properly validated, accurately controlled sterilization process is not the only factor

associated with the provision of reliable assurance that a processed medical device is sterile and, in

this regard, suitable for its intended use. Attention is also given to a number of factors including:

a) the microbiological status of incoming raw materials or components;

b) the validation and routine control of any cleaning and disinfection procedures used on the medical

device;
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c) the control of the environment in which the medical device is manufactured, assembled and

packaged;
d) the control of sterilizer and processes;
e) the control of personnel and their hygiene;
f) the manner and materials in which the medical device is packaged;
g) the conditions under which the medical device is transported and stored;
h) the material and design of the medical devices being processed.

The type of contaminants on a medical device to be sterilized varies, and this influences the effectiveness

of a sterilization process. Medical devices used in a health care facility and that are being presented

for sterilization in accordance with the manufacturer's instructions (see ISO/FDIS 17664-1:2021)

should be regarded as special cases. There is the potential for such medical devices to possess a wide

range of contaminating microorganisms and residual inorganic or organic contaminants in spite of

the application of a cleaning process. Hence, particular attention has to be given to the validation and

control of the cleaning and disinfection processes used during reprocessing.

The requirements are the normative parts of this document with which conformance is claimed. The

guidance given in Annex E is not normative and is not provided as a checklist for auditors. The guidance

provides explanations and methods that are regarded as being a suitable means for conforming with

the requirements. Methods other than those given in the guidance can be used if they are effective in

achieving conformance with the requirements of this document.

The development, validation and routine control of a sterilization process comprise a number of discrete

but interrelated activities, for example, calibration, maintenance, product definition, process definition,

installation qualification, operational qualification and performance qualification. While the activities

required by this document have been grouped together and are presented in a particular order, this

document does not require that the activities be performed in the order that they are presented. The

activities required are not necessarily sequential, as the programme of development and validation

can be iterative. The responsibility for carrying out the activities required by this document will vary

from case to case. This document requires that the responsibilities of the various parties be defined

(see 4.1) but does not specify to whom the responsibilities are allocated. Annex E provides guidance on

allocation of responsibility.

Like other standardized low temperature sterilization processes such as ethylene oxide (see ISO 11135)

or low temperature steam and formaldehyde (see ISO 25424), the VH2O2 sterilization processes

are specified by physical and chemical parameters and can be verified using physical, chemical and

microbiological means.

Sterilization processes to which this document applies should consider not only technical issues but also

the environmental impact. Activities required by this document could contribute to an environmental

burden that can be minimised by planning and combining tests. Additional information regarding

environmental impact is provided in Annex G.

NOTE 1 Specifications on operating safety are addressed in EN 61010-1, EN 61010-2-040 and are not repeated

in this document. EN 60204-1 can also apply.

NOTE 2 Requirements on occupational safety are not specified in this document (see 1.2.4).

This document has two distinct applications:

— for manufacturers and users of VH2O2 sterilization processes in the health care facility;

— for manufacturers and users of VH2O2 sterilization processes in the industrial setting.

In this document, the conjunctive “or” is used as an “inclusive or” so a statement is true if any

combination of the conditions is true.
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The verbal forms used in this document conform to usage described in ISO/IEC Directives, Part 2. For

the purposes of this document, the auxiliary verb:

— “shall” means that conformance with a requirement or a test is mandatory for conformance with

this document;

— “should” means that conformance with a requirement or a test is recommended but is not mandatory

for conformance with this document;

— “may” is used to describe permission (e.g. a permissible way to achieve conformance with a

requirement or test);
— "can" is used to describe a possibility or capability; and
— "must" is used to express an external constraint.
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oSIST ISO/DIS 22441:2021
DRAFT INTERNATIONAL STANDARD ISO/DIS 22441:2021(E)
Sterilization of health care products — Low temperature
vaporized hydrogen peroxide — Requirements for
the development, validation and routine control of a
sterilization process for medical devices
1 Scope
1.1 Inclusions

1.1.1 This document provides requirements for the development, validation and routine monitoring

and control of a low temperature sterilization process for medical devices using vaporized hydrogen

peroxide (VH2O2) as the sterilizing agent.

1.1.2 This document is intended to be applied by process developers, manufacturers of sterilization

equipment, manufacturers of medical devices to be sterilized, organizations performing process

validation of VH2O2 sterilization, and organizations responsible for sterilizing medical devices.

NOTE VH2O2 sterilizers can be used in both health care and industrial facilities, and this document

acknowledges the similarities and differences between the two applications.
1.2 Exclusions

1.2.1 Processes that use other sterilizing agents, or hydrogen peroxide in combination with other

chemicals as the sterilizing agent are not addressed in this document.
NOTE See ISO 14937 for guidance on validation of such processes.

1.2.2 This document does not specify requirements for development, validation and routine control

of a process for inactivating the causative agents of spongiform encephalopathies such as scrapie,

bovine spongiform encephalopathy and Creutzfeldt-Jakob disease. Specific recommendations have been

produced in particular countries for the processing of materials potentially contaminated with these

agents.

NOTE Some VH2O2 sterilizers have processes that demonstrate some level of inactivation of the causative

agents of spongiform encephalopathies such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-

Jakob Disease. However this inactivation is process, cycle, and test protocol specific, therefore this inactivation is

outside the scope of this document, and no specific test methods are provided.

1.2.3 This document does not specify requirements for designating a medical device as sterile.

NOTE Attention is drawn to national or regional requirements for designating medical devices as “sterile”.

See for example EN 556–1 or ANSI/AAMI ST67.

1.2.4 This document does not specify requirements for occupational safety associated with the design

and operation of VH2O2 sterilization equipment.

NOTE For further information on safety, see examples in the bibliography. National or regional regulations

can also exist.
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1.2.5 This document does not apply to the contents of contained product, i.e. product for which the

environment within the sterilizer during any stage of the sterilization process does not come into direct

contact with the product, such as a solution in a sealed bottle.

1.2.6 This document does not cover hydrogen peroxide decontamination systems for use in rooms,

enclosures or environmental spaces.

NOTE These decontamination systems operate at ambient conditions (e.g. temperature and pressure) and

in general utilise an approach that is different to that of vaporized hydrogen peroxide (VH2O2) sterilization

processes addressed in this document.
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 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk

management process

ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for

leachable substances

ISO 11138-1:2017, Sterilization of health care products — Biological indicators — Part 1: General

requirements

ISO 11140-1, Sterilization of health care products — Chemical indicators — Part 1: General requirements

ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials,

sterile barrier systems and packaging systems

ISO 11607-2, Packaging for terminally sterilized medical devices — Part 2: Validation requirements for

forming, sealing and assembly processes

ISO 11737-1, Sterilization of health care products — Microbiological methods — Part 1: Determination of a

population of microorganisms on products

ISO 11737-2, Sterilization of health care products — Microbiological methods — Part 2: Tests of sterility

performed in the definition, validation and maintenance of a sterilization process

3 Terms and definitions
For the purposes of this document, the following terms and definitions 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 https:// www .electropedia .org/
3.1
bioburden

population of viable microorganisms on or in product and/or sterile barrier system

[SOURCE: ISO 11139:2018, 3.23]
1) ISO 11138-1 gives general
...