ISO/DIS 22441

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

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

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

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

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

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

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

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

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

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

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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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

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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

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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

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

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

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

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

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

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

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

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:

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

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

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

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

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

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

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

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

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

— 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

The verbal forms used in this document conform to usage described in ISO/IEC Directives, Part 2. For

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

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

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

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

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

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

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

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

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”.

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

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

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

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

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

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

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

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

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,

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

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

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

ISO and IEC maintain terminological databases for use in standardization at the following addresses:

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