prEN ISO 13004

Sterilization of health care products - Radiation - Substantiation of selected sterilization dose: Method VDmaxSD (ISO 13004:2022)

Adoption of ISO 13004:2022 – This is currently in FDIS and will be publishing in October 2022.
This document describes a method for substantiating a selected sterilization dose of 17,5,
20, 22,5, 27,5, 30, 32,5 or 35 kGy that achieves a sterility assurance level (SAL) of 10−6 or less for radiation
sterilization of health care products. This Technical Specification also specifies a method of sterilization
dose audit used to demonstrate the continued effectiveness of the substantiated sterilization dose.
NOTE Selection and substantiation of the sterilization dose is used to meet the requirements for establishing
the sterilization dose within process definition in ISO 11137-1.

Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Bestätigung der gewählten Sterilisationsdosis: Methode VDmaxSD (ISO 13004:2022)

Stérilisation des produits de santé - Irradiation - Justification de la dose stérilisante choisie: Méthode DVmaxDS (ISO 13004:2022)

Sterilizacija izdelkov za zdravstveno nego - Sevanje - Utemeljitev izbrane doze sterilizacije: metoda VDmaxSD (ISO 13004:2022)

General Information

• Status: Not Published
• Publication Date: 23-Sep-2025
• ICS: 11.080.01 - Sterilization and disinfection in general
• Technical Committee: CEN/TC 204 - Sterilization of medical devices
• Drafting Committee: CEN/TC 204 - Sterilization of medical devices
• Current Stage: 4060 - Closure of enquiry - Enquiry
• Start Date: 25-May-2023
• Due Date: 24-Dec-2023
• Completion Date: 25-May-2023
• Ref Project: oSIST prEN ISO 13004:2023 - Sterilization of health care products - Radiation - Substantiation of selected sterilization dose: Method VDmaxSD (ISO 13004:2022)

Relations

• Revises: CEN ISO/TS 13004:2014 - Sterilization of health care products - Radiation - Substantiation of selected sterilization dose: Method VDmaxSD (ISO/TS 13004:2013)
• Effective Date: 19-Jan-2023

Standards Content (Sample)

SLOVENSKI STANDARD
oSIST prEN ISO 13004:2023
01-maj-2023
Sterilizacija izdelkov za zdravstveno nego - Sevanje - Utemeljitev izbrane doze
sterilizacije: metoda VDmaxSD (ISO 13004:2022)

Sterilization of health care products - Radiation - Substantiation of selected sterilization

dose: Method VDmaxSD (ISO 13004:2022)

Sterilisation von Produkten für die Gesundheitsfürsorge - Strahlen - Bestätigung der

gewählten Sterilisationsdosis: Methode VDmaxSD (ISO 13004:2022)

Stérilisation des produits de santé - Irradiation - Justification de la dose stérilisante

choisie: Méthode DVmaxDS (ISO 13004:2022)
Ta slovenski standard je istoveten z: prEN ISO 13004
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
oSIST prEN ISO 13004:2023 en,fr,de

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

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oSIST prEN ISO 13004:2023
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oSIST prEN ISO 13004:2023
INTERNATIONAL ISO
STANDARD 13004
First edition
2022-10
Sterilization of health care products —
Radiation — Substantiation of
selected sterilization dose: Method
max
Stérilisation des produits de santé — Irradiation — Justification de la
dose stérilisante choisie: Méthode DV
max
Reference number
ISO 13004:2022(E)
© ISO 2022
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oSIST prEN ISO 13004:2023
ISO 13004:2022(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2022

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
© ISO 2022 – All rights reserved
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oSIST prEN ISO 13004:2023
ISO 13004:2022(E)
Contents Page

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

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

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

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

3 Terms and definitions .................................................................................................................................................................................... 1

4 Definition and maintenance of product families for sterilization dose substantiation

and sterilization dose auditing.............................................................................................................................................................5

4.1 General ........................................................................................................................................................................................................... 5

4.2 Defining product families ............................................................................................................................................................. 5

4.3 Designation of product to represent a product family ........................................................................................ 6

4.3.1 Product to represent a product family ........................................................................................................... 6

4.3.2 Master product ..................................................................................................................................................................... 7

4.3.3 Equivalent product ........................................................................................................................................................... 7

4.3.4 Simulated product ............................................................................................................................................................. 7

4.4 Maintaining product families .................................................................................................................................................... 8

4.4.1 Periodic review .................................................................................................................................................................... 8

4.4.2 Modification to either product or manufacturing process, or both ..................................... 8

4.4.3 Records ....................................................................................................................................................................................... 8

4.5 Consequence of failure of sterilization dose substantiation or sterilization dose

audit.................................................................................................................................................................................................................. 8

5 Selection and testing of product for substantiating and auditing a selected

sterilization dose ................................................................................................................................................................................................. 8

5.1 Nature of product ................................................................................................................................................................................. 8

5.2 Sample item portion (SIP) ............................................................................................................................................................ 9

5.3 Manner of sampling ......................................................................................................................................................................... 10

5.4 Microbiological testing ................................................................................................................................................................. 11

5.5 Irradiation ............................................................................................................................................................................................... 11

6 Method VD — Substantiation of a selected sterilization dose of 17,5 kGy,
max

20 kGy, 22,5 kGy, 27,5 kGy, 30 kGy, 32,5 kGy or 35 kGy ............................................................................................12

6.1 Rationale ...................................................................................................................................................................................................12

6.2 Procedure for Method VD for multiple production batches ..........................................................12

max

6.2.1 General .....................................................................................................................................................................................12

6.2.2 Stage 1: Obtain samples of product ................................................................................................................ 13

6.2.3 Stage 2: Determine average bioburden .......................................................................................................13

6.2.4 Stage 3: Obtain the selected sterilization dose ....................................................................................13

6.2.5 Stage 4: Obtain VD .......................................................................................................................................... 14

max

6.2.6 Stage 5: Perform verification dose experiment ................................................................................... 15

6.2.7 Stage 6: Interpretation of results ..................................................................................................................... 15

6.2.8 Confirmatory verification dose experiment ........................................................................................... 16

6.3 Procedure for Method VD for a single production batch ................................................................. 17

max

6.3.1 Rationale ................................................................................................................................................................................. 17

6.3.2 General ..................................................................................................................................................................................... 17

6.3.3 Stage 1: Obtain samples of product ................................................................................................................ 17

6.3.4 Stage 2: Determine average bioburden ....................................................................................................... 18

6.3.5 Stage 3: Obtain the selected sterilization dose .................................................................................... 18

6.3.6 Stage 4: Obtain VD ........................................................................................................................................... 19

max

6.3.7 Stage 5: Perform verification dose experiment ................................................................................... 19

6.3.8 Stage 6: Interpretation of results ..................................................................................................................... 19

6.3.9 Confirmatory verification dose experiment ........................................................................................... 20

7 Maintaining process effectiveness ................................................................................................................................................21

iii
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oSIST prEN ISO 13004:2023
ISO 13004:2022(E)

7.1 General ........................................................................................................................................................................................................ 21

7.2 Frequency of determination of bioburden .................................................................................................................. 21

7.3 Sterilization dose audit ................................................................................................................................................................ 21

7.3.1 Frequency .............................................................................................................................................................................. 21

7.3.2 Outcome ..................................................................................................................................................................................22

7.3.3 Procedure for auditing a sterilization dose substantiated using Method

VD .................................................................................................................................................................................... 22

max

7.3.4 Failure of a sterilization dose audit ................................................................................................................ 25

8 Tables of values for SIP ........................................................................................................................................... ....................................26

9 Worked examples .............................................................................................................................................................................................51

9.1 Substantiation of a selected sterilization dose of 17,5 kGy (SIP less than 1,0) ........................... 51

9.2 Substantiation of a selected sterilization dose of 30 kGy (SIP equal to 1,0) ................................. 52

9.3 Sterilization dose audit for a sterilization dose substantiated using ................................................ 52

22,5

9.4 Method VD .............................................................................................................................................................................. 52

max

Bibliography .............................................................................................................................................................................................................................54

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oSIST prEN ISO 13004:2023
ISO 13004:2022(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 198, Sterilization of health care products.

This first edition cancels and replaces ISO/TS 13004:2013.
The main changes are as follows:

— guidance is offered for determination of an SIP for bulk materials such as powders, liquids and gels;

— 5.3.3 and 5.3.4 have been reworded to match language in ISO 11137-2;
— the NOTE in 5.4.1 has been removed;
— 7.2 has been replaced with a reference to requirements in ISO 11137-1;

— guidance has been added for when to re-substantiate the sterilization dose based on shifts in

bioburden.

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 2022 – All rights reserved
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oSIST prEN ISO 13004:2023
ISO 13004:2022(E)
Introduction

This document is intended to be used in conjunction with ISO 11137-1. One of the activities encompassed

within process definition in ISO 11137-1 is the option to select and substantiate a sterilization dose to

be applied to health care products.

ISO 11137-2 includes Method VD for the substantiation of 25 kGy as a sterilization dose (termed

max

Method VD ) for product with an average bioburden less than or equal to 1 000 and Method

max

VD for the substantiation of 15 kGy as a sterilization dose for product with an average bioburden

max
less than or equal to 1,5.

This document extends the methods of selection and substantiation of a sterilization dose specified in

ISO 11137-2. It provides a methodology for the substantiation of selected sterilization doses of 17,5 kGy,

20 kGy, 22,5 kGy, 27,5 kGy, 30 kGy, 32,5 kGy and 35 kGy, each of which is valid only for a specified upper

limit of average bioburden.

NOTE Selected sterilization doses of 25 kGy and 15 kGy are not included in this document. The seven

methods in this document follow the same technical steps as the methods given in ISO 11137-2 for selection

and substantiation of sterilization doses of 25 kGy and 15 kGy. However, the descriptive text in this document

has been modified to better communicate the methods and hence the text occasionally differs from that in

ISO 11137-2.

The method described in this document is for substantiation of a selected sterilization dose to achieve a

−6 20

sterility assurance level (SAL) of 10 or less at that dose (e.g. Method VD for a selected sterilization

max

dose of 20 kGy). The application of the method is not limited by production batch size or production

frequency, and the number of product items irradiated in the verification dose experiment remains

constant. The method is founded on and embodies the following three principles:

— existence of a direct link between the outcome of the verification dose experiment and the attainment

of an SAL of 10 at the selected sterilization dose;

— possession of a level of conservativeness at least equal to that of the standard distribution of

resistances (SDR);

— for a given bioburden, use of a maximal verification dose (VD ) corresponding to substantiation

max
of a selected sterilization dose.
[7]

This approach to sterilization dose substantiation was first outlined by Kowalski and Tallentire

and, from subsequent evaluations involving computational techniques (Kowalski, Aoshuang and

[8] [9]

Tallentire ) and field evaluations (Kowalski et al. ), it was concluded that the method is soundly

based. An overview of the method and aspects of implementation are provided in Kowalski and

[10][11] SD

Tallentire. Application of the Method VD approach to doses other than 25 kGy is discussed

max
[12][13]
in Kowalski and Tallentire .

The method described here and designated Method VD procedurally comprises elements that

max

closely parallel those of dose setting Method 1 described in ISO 11137-2. One key area of difference

is the number of product items used in the verification dose experiment. In the computer evaluations

referred to above, changing the verification SAL value had little effect on the substantiation outcome

and this finding led to a sample size of 10 product items being chosen for subsequent field evaluations

and, ultimately, for inclusion in this document.

Manufacturers of health care products who intend to use this specification are reminded that the

requirements contained in the ISO 11137 series apply to the manufacture and control of production

batches destined for radiation sterilization. In particular, one requirement states that products have

to be manufactured in circumstances such that the bioburden is controlled. The control of the quality

of raw materials, the manufacturing environment, the health, hygiene and attire of personnel and for

establishing the basic properties of packaging material should be maintained.
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oSIST prEN ISO 13004:2023
INTERNATIONAL STANDARD ISO 13004:2022(E)
Sterilization of health care products — Radiation —
Substantiation of selected sterilization dose: Method
max
1 Scope

This document describes a method for substantiating a selected sterilization dose of 17,5 kGy, 20 kGy,

22,5 kGy, 27,5 kGy, 30 kGy, 32,5 kGy or 35 kGy that achieves a sterility assurance level (SAL) of 10

or less for radiation sterilization of health care products. This document also specifies a method

of sterilization dose audit used to demonstrate the continued effectiveness of the substantiated

sterilization dose.

NOTE 1 Selection and substantiation of the sterilization dose is used to meet the requirements for establishing

the sterilization dose within process definition in ISO 11137-1.

This document does not apply to other sterilization doses than the substantiation of a selected

sterilization dose of 17,5 kGy, 20 kGy, 22,5 kGy, 27,5 kGy, 30 kGy, 32,5 kGy or 35 kGy. The method is

not used for the substantiation of a selected sterilization dose if the average bioburden of the entire

product item exceeds the limit specified for the selected sterilization dose (see Table 3).

NOTE 2 The methods for substantiation of selected sterilization doses of 25 kGy and 15 kGy are not included

in this document. They are described in ISO 11137-2.

If the decision is made to use this method of sterilization dose establishment, the method is intended to

be followed in accordance with the requirements (shall) and guidance (should) stipulated herein.

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 11137-1:2006, Sterilization of health care products — Radiation — Part 1: Requirements for

development, validation and routine control of a sterilization process for medical devices

ISO 11737-1:2018, 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 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/
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oSIST prEN ISO 13004:2023
ISO 13004:2022(E)
3.1
absorbed dose
dose

quantity of ionizing radiation energy imparted per unit mass of a specified material

Note 1 to entry: The unit of absorbed dose is the gray (Gy), where 1 Gy is equivalent to the absorption of 1 J/kg.

Note 2 to entry: For the purposes of this document, the term dose is used to mean absorbed dose.

[SOURCE: ISO 11139:2018, 3.3, modified — The term "dose" was added. Notes 1 to 2 to entry were

added.]
3.2
batch

defined quantity of a product intended or purported to be uniform in character and quality produced

during a specified cycle of manufacture
[SOURCE: ISO 11139:2018, 3.21]
3.3
bioburden

population of viable microorganisms (3.11) on or in a product and/or sterile barrier system (3.16)

[SOURCE: ISO 11139:2018, 3.23]
3.4
correction
action to eliminate a detected nonconformity

Note 1 to entry: A correction can be made in conjunction with corrective action (3.5).

[SOURCE: ISO 11139:2018, 3.64, modified — In the Note 1 to entry, "in advance of, in conjunction with,

or after" has been replaced by "in conjunction with".]
3.5
corrective action
action to eliminate the cause of a nonconformity and to prevent recurrence
Note 1 to entry: There can be more than one cause for a nonconformity.

Note 2 to entry: Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent

occurrence.

Note 3 to entry: There is a distinction between correction (3.4) and corrective action (3.5).

[SOURCE: ISO 11139:2018, 3.65, modified — Note 3 to entry has been added.]
3.6
dose mapping

measurement of dose distribution and variability in material irradiated under specified conditions

[SOURCE: ISO 11139:2018, 3.87]
3.7
false positive

test result interpreted as growth arising from product, or portion thereof, tested when either growth

resulted from extraneous microbial contamination or turbidity occurred from interaction between the

product, or portions thereof, and the test medium
[SOURCE: ISO 11137-2:2013, 3.1.3]
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oSIST prEN ISO 13004:2023
ISO 13004:2022(E)
3.8
health care product(s)

medical device (3.9), including in vitro diagnostic medical device, or medicinal product, including

biopharmaceutical
[SOURCE: ISO 11139:2018, 3.132]
3.9
medical device

instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, or software

material, or other similar or related article, intended by the manufacturer to be used, alone or in

combination, for human beings, for one or more of the specific medical purpose(s) of:

— diagnosis, prevention, monitoring, treatment, or alleviation of disease;

— diagnosis, monitoring, treatment, alleviation of, or compensation for an injury;

— investigation, replacement, modification, or support of the anatomy, or of a physiological process;

— supporting or sustaining life;
— control of conception;
— disinfection of medical devices;

— providing information by means of in vitro examination of specimens derived from the human

body;

and does not achieve its primary intended action by pharmacological, immunological, or metabolic

means, but which may be assisted in its intended function by such means
[SOURCE: ISO 11139:2018, 3.166, modified — Note 1 to entry has been deleted.]
3.10
Method VD
max

procedure for sterilization dose substantiation that uses the maximal verification dose (3.23) for a given

bioburden (3.3), consistent with the attainment of a sterility assurance level (SAL) of 10 at a selected

sterilization dose

Note 1 to entry: The substantiation method is generally referred to as Method VD , where SD takes the value

max
of the selected sterilization dose.

Note 2 to entry: VD is the maximal verification dose (3.23) for a particular selected sterilization dose (SD)

max
obtained in using Method VD .
max
SD Dster
Note 3 to entry: The term VD may be used interchangeably with the term VD .
max max
3.11
microorganism
entity of microscopic size, encompassing bacteria, fungi, protozoa and viruses

Note 1 to entry: A specific standard might not require demonstration of the effectiveness of the sterilization

process in inactivating all types of microorganisms, identified in the definition above, for validation and/or

routine control of the sterilization process.
[SOURCE: ISO 11139:2018, 3.176, modified — Note 1 to entry was added.]
3.12
packaging system
combination of the sterile barrier system (3.16) and protective packaging
[SOURCE: ISO 11139:2018, 3.192]
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oSIST prEN ISO 13004:2023
ISO 13004:2022(E)
3.13
positive test of sterility

test result for which there is detectable microbial growth from product, or portion thereof, subjected to

a test of sterility (3.22)
[SOURCE: ISO 11137-2:2013, 3.1.8]
3.14
product
tangible result of a process

EXAMPLE Raw material(s), intermediate(s), sub-assembly(ies), health care product(s) (3.8).

[SOURCE: ISO 11139:2018, 3.217]
3.15
sample item portion
SIP
specified part of a health care product (3.8) that is tested
[SOURCE: ISO 11139:2018, 3.240]
3.16
sterile barrier system

minimum package that minimizes the risk of ingress of microorganisms (3.11) and allows aseptic

presentation of the sterile contents at the point of use
[SOURCE: ISO 11139:2018, 3.272]
3.17
sterility
state of being free from viable microorganisms (3.11)

Note 1 to entry: In practice, no such absolute statement regarding the absence of microorganisms can be proven

[see sterilization (3.19)].
[SOURCE: ISO 11139:2018, 3.274]
3.18
sterility assurance level
SAL

probability of a single viable microorganism (3.11) occurring on an item after sterilization

Note 1 to entry: It is expressed as the negative exponent to the base 10.
[SOURCE: ISO 11139:2018, 3.275
3.19
sterilization
validated process used to render product free from viable microorganisms (3.11)

Note 1 to entry: In a sterilization process, the nature of microbial inactivation is exponential and thus the survival

of a microorganism on an individual item can be expressed in terms of probability. While this probability can be

reduced to a very low number it can never be reduced to zero [see sterility assurance level (3.18)].

[SOURCE: ISO 11139:2018, 3.277]
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oSIST prEN ISO 13004:2023
ISO 13004:2022(E)
3.20
sterilization dose
ster
mini
...