BS Iso 13004-2022

BS ISO 13004:2022
BSI Standards Publication
Sterilization of health care products —

Radiation — Substantiation of selected
sterilization dose: Method VDmaxSD
BS ISO 13004:2022 BRITISH STANDARD
National foreword
This British Standard is the UK implementation of ISO 13004:2022. It
supersedes PD CEN ISO/TS 13004:2014, which is withdrawn.
The UK participation in its preparation was entrusted to Technical
Committee CH/198, Sterilization and Associated Equipment
and Processes.
A list of organizations represented on this committee can be obtained on
request to its committee manager.
Contractual and legal considerations
This publication has been prepared in good faith, however no
representation, warranty, assurance or undertaking (express or
implied) is or will be made, and no responsibility or liability is or will be
accepted by BSI in relation to the adequacy, accuracy, completeness or
reasonableness of this publication. All and any such responsibility and
liability is expressly disclaimed to the full extent permitted by the law.
This publication is provided as is, and is to be used at the
recipient’s own risk.
The recipient is advised to consider seeking professional guidance with
respect to its use of this publication.
This publication is not intended to constitute a contract. Users are
responsible for its correct application.
© The British Standards Institution 2022
Published by BSI Standards Limited 2022
ISBN 978 0 539 16522 7
ICS 11.080.01
Compliance with a British Standard cannot confer immunity from
legal obligations.
This British Standard was published under the authority of the
Standards Policy and Strategy Committee on 31 October 2022.
Amendments/corrigenda issued since publication

Date Text affected
BS ISO 13004:2022
INTERNATIONAL ISO
STANDARD 13004
First edition
2022-10-07
Sterilization of health care products —

Radiation — Substantiation of selected
sterilization dose: Method VDmaxSD
Stérilisation des produits de santé — Irradiation — Justification de la
dose stérilisante choisie: Méthode DVmaxDS
Reference number
ISO 13004:2022(E)
© ISO 2022
BS ISO 13004:2022
ISO 13004:2022(E)

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ii © ISO 2022 – All rights reserved

BS ISO 13004:2022
ISO 13004:2022

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...................................................................................................................................................... 7
4.4.1 Periodic review.................................................................................................................................................................. 7
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 max SD — 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..............................................................................................11
6.1 Rationale.................................................................................................................................................................................................... 11
6.2 Procedure for Method VDmaxSD for multiple production batches............................................................ 12
6.2.1 General................................................................................................................................................................................... 12
6.2.2 Stage 1: Obtain samples of product............................................................................................................... 12
6.2.3 Stage 2: Determine average bioburden...................................................................................................... 12
6.2.4 Stage 3: Obtain the selected sterilization dose.................................................................................... 13
6.2.5 Stage 4: Obtain VD max SD ......................................................................................................................................... 14
6.2.6 Stage 5: Perform verification dose experiment................................................................................... 14
6.2.7 Stage 6: Interpretation of results..................................................................................................................... 15
6.2.8 Confirmatory verification dose experiment........................................................................................... 16
6.3 Procedure for Method VDmaxSD for a single production batch.................................................................... 17
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...................................................................................................... 17
6.3.5 Stage 3: Obtain the selected sterilization dose.................................................................................... 18
6.3.6 Stage 4: Obtain VDmaxSD.......................................................................................................................................... 18
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
7.1 General......................................................................................................................................................................................................... 21
7.2 Frequency of determination of bioburden.................................................................................................................... 21
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7.3 Sterilization dose audit.................................................................................................................................................................. 21

7.3.1 Frequency............................................................................................................................................................................ 21
7.3.2 Outcome................................................................................................................................................................................ 21
7.3.3 Procedure for auditing a sterilization dose substantiated using
Method VDmaxSD............................................................................................................................................................. 22
7.3.4 Failure of a sterilization dose audit............................................................................................................... 25
8 Tables of values for SIP................................................................................................................................................................................26
9 Worked examples..............................................................................................................................................................................................50
9.1 Substantiation of a selected sterilization dose of 17,5 kGy (SIP less than 1,0)............................. 50
9.2 Substantiation of a selected sterilization dose of 30 kGy (SIP equal to 1,0).................................... 51
9.3 Sterilization dose audit for a sterilization dose substantiated using ................................................... 52
9.4 Method VDmax22,5............................................................................................................................................................................... 52
Bibliography.............................................................................................................................................................................................................................. 54
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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 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.
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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 VDmaxSD for the substantiation of 25 kGy as a sterilization dose (termed
Method VDmax25) for product with an average bioburden less than or equal to 1 000 and Method
VDmax15 for the substantiation of 15 kGy as a sterilization dose for product with an average bioburden
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 sterility assurance level (SAL) of 10−6 or less at that dose (e.g. Method VDmax20 for a selected
sterilization 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 10−6 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 (VDmax) corresponding to substantiation
of a selected sterilization dose.
This approach to sterilization dose substantiation was first outlined by Kowalski and Tallentire[7]
and, from subsequent evaluations involving computational techniques (Kowalski, Aoshuang and
Tallentire[8]) and field evaluations (Kowalski et al.[9]), it was concluded that the method is soundly
based. An overview of the method and aspects of implementation are provided in Kowalski and
Tallentire.[10][11] Application of the Method VDmaxSD approach to doses other than 25 kGy is discussed
in Kowalski and Tallentire[12][13].
The method described here and designated Method VDmaxSD procedurally comprises elements that
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.
vi © ISO 2022 – All rights reserved

BS ISO 13004:2022
INTERNATIONAL STANDARD ISO 13004:2022
Sterilization of health care products — Radiation —

Substantiation of selected sterilization dose:
Method VDmaxSD
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 10−6
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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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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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 VDmax
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 10−6 at a selected
sterilization dose
Note 1 to entry: The substantiation method is generally referred to as Method VDmax SD, where SD takes the value
of the selected sterilization dose.
Note 2 to entry: VDmax SD is the maximal verification dose (3.23) for a particular selected sterilization dose (SD)
obtained in using Method VDmax SD.
Note 3 to entry: The term VDmax SD may be used interchangeably with the term VDmaxDster.
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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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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3.20
sterilization dose
SD
Dster
minimum dose to achieve the specified requirements for sterility (3.17)
[SOURCE: ISO 11139:2018, 3.280]
3.21
sterilization dose audit
exercise undertaken to confirm the appropriateness of an established sterilization dose
[SOURCE: ISO 11139:2018, 3.281]
3.22
test of sterility
technical operation performed as part of development, validation or requalification to determine the
presence or absence of viable microorganisms (3.11) on product or portion thereof
[SOURCE: ISO 11139:2018, 3.299]
3.23
verification dose
dose of radiation predicted to give a predetermined sterility assurance level (SAL) (3.18) greater than or
equal to 10−2 used in establishing the sterilization dose
Note 1 to entry: For the purpose of this document, this predetermined SAL is 10−1.
[SOURCE: ISO 11139:2018, 3.315, modified — Note 1 to entry was added.]
4 Definition and maintenance of product families for sterilization dose

substantiation and sterilization dose auditing
4.1 General
The establishment of a sterilization dose, for which sterilization dose selection and substantiation can
be undertaken, and the carrying out of sterilization dose audits are activities that are part of process
definition and maintaining process effectiveness (see ISO 11137‑1). For these activities, product may
be grouped into families. Definition of product families is based principally on the numbers and types
of microorganisms on or in product (the bioburden), the type being indicative of the microorganism’s
resistance to radiation (see ISO 11737‑1). Variables such as density and product configuration within its
packaging system are not considered in the establishment of these product families because they are
not factors that influence bioburden.
In using product families for establishing the sterilization dose and for carrying out sterilization
dose audits, it is important to be aware of the reduction in the ability to detect an inadvertent change
within the manufacturing process that influences the effectiveness of sterilization. Furthermore, with
the use of a single product to represent the product family, it is possible that changes that occur in
other members of the product family will not be detected. The effect of a reduction on ability to detect
changes in other members of the product family should be evaluated and a plan for maintaining product
families developed and implemented before proceeding.
4.2 Defining product families
4.2.1 The criteria for defining a product family shall be documented. Product shall be assessed against
these criteria and the similarities between potential product family members considered. Consideration
shall include all product-related variables that affect bioburden, including, but not limited to:

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a) nature and sources of raw materials, including the effect, if any, of raw materials that can be
sourced from more than one location;
b) components;
c) product design and size;
d) manufacturing processes;
e) manufacturing equipment;
f) manufacturing environment;
g) manufacturing location.
The outcome of the assessment and considerations shall be recorded in accordance with
ISO 11137‑1:2006, 4.1.2.
4.2.2 Product shall only be included in a product family if it is demonstrated that the product-related
variables (see 4.2.1) are similar and under control.
4.2.3 To include product within a product family, it shall be demonstrated that bioburden comprises
similar numbers and types of microorganisms.
4.2.4 Inclusion of product from more than one manufacturing location in a product family shall be
specifically justified and recorded in accordance with ISO 11137‑1:2006, 4.1.2. Consideration shall be
given to the effect on bioburden of:
a) geographic and/or climatic differences between locations;

b) any differences in the control of the manufacturing processes or environment;
c) sources of raw materials and processing adjuvants (e.g. water).
4.3 Designation of product to represent a product family
4.3.1 Product to represent a product family
4.3.1.1 The number and types of microorganisms on or in product shall be used as the basis for
selecting product to represent a product family.
4.3.1.2 A product family shall be represented by:
a) a master product (see 4.3.2), or

b) an equivalent product (see 4.3.3), or
c) a simulated product (see 4.3.4).
4.3.1.3 A formal, documented assessment shall be undertaken to decide which of the three potential
representative products in 4.3.1.2 is appropriate. In this assessment, consideration shall be given to
the following:
a) number of microorganisms comprising the bioburden;

b) types of microorganisms comprising the bioburden;
c) environment in which the microorganisms occur;
d) size of product;

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e) number of components;
f) complexity of product;
g) degree of automation during manufacture;
h) manufacturing environment.
4.3.2 Master product
A member of a product family shall only be considered a master product if assessment (see 4.3.1.3)
indicates that the member presents a challenge to the sterilization process that is greater than that of
all other product family members. In some situations, there can be several products within the product
family, each of which can be considered as the master product. In such circumstances, any one of these
products may be selected as the master product to represent the family, either
a) at random, or
b) according to a documented procedure to include the different products each of which can be
considered as the master product.
4.3.3 Equivalent product
A group of product shall only be considered equivalent if assessment (see 4.3.1.3) indicates that group
members require the same sterilization dose. Selection of the equivalent product to represent the
family shall be either
a) at random, or
b) in accordance with a documented procedure to include different members of the product family.
The manufacturing volume and availability of product should be considered in the selection of the
equivalent product to represent the product family.
4.3.4 Simulated product
A simulated product shall only represent a product family if it constitutes an equivalent or greater
challenge to the sterilization process than that provided by members of the product family. Simulated
product shall be packaged in a manner and with materials used for the actual product.
NOTE A simulated product is not intended for clinical use; it is fabricated solely for the establishment or
maintenance of the sterilization dose.
A simulated product may be:

a) one that is similar to the actual product in terms of materials and size, and subjected to similar
manufacturing processes, e.g. a piece of the material, used for implants, that goes through the
entire manufacturing process, or
b) a combination of components from product within the product family that would not typically
be combined for use, e.g. a tubing set containing multiple filters, clamps and stopcocks that are
components of other products within the product family.
4.4 Maintaining product families
4.4.1 Periodic review
Review shall be performed at a specified frequency to ensure that product families and product used to
represent each product family remain valid. Responsibility for reviews of either product or processes,
or both that can affect membership of product families shall be allocated to competent personnel. Such

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review shall be performed at least annually. The outcome of the review shall be recorded in accordance
with ISO 11137‑1:2006, 4.1.2.
4.4.2 Modification to either product or manufacturing process, or both
Modifications to product, such as raw materials (nature and source), components or product design
(including size), and/or modifications to the manufacturing process, e.g. equipment, environment or
location, shall be assessed through a formal, documented change control system. Such modifications
can alter the basis on which the product family was defined or the basis on which the selection of
product to represent the product family was made. Significant changes can require definition of a new
product family or the selection of a different representative product.
4.4.3 Records
Records of product families shall be retained in accordance with ISO 11137‑1:2006, 4.1.2.
4.5 Consequence of failure of sterilization dose substantiation or

sterilization dose audit
In the event of failure during substantiation of a selected sterilization dose or performance of the
sterilization dose audit for a product family, all members of that family shall be considered to be
affected. Subsequent actions shall apply to all members comprising the product family.
5 Selection and testing of product for substantiating and auditing a selected

sterilization dose
5.1 Nature of product
5.1.1 Product for sterilization can consist of:
a) an individual health care product in its packaging system;

b) a set of components presented in a packaging system, which are assembled at the point of use to
form the health care product, together with accessories required to use the assembled product;
c) a number of identical health care products in their packaging system;
d) a kit comprising a variety of procedure-related health care products.
Product items for sterilization dose substantiation and for sterilization dose auditing shall be taken in
accordance with Table 1.
Table 1 — Nature of product items for sterilization dose substantiation and for sterilization
dose auditing
Item for bioburden determination
Product type Rationale
and verification dose experiment
Individual health care product in its Each health care product is used
Individual health care product
packaging system independently in clinical practice.
Components are assembled as a
Set of components in a packaging Combination of all components of
product and used together in clini-
system the product
cal practice.
a In dose establishment, the sterilization dose is chosen based on the health care product requiring the highest
sterilization dose.

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Item for bioburden determination

Product type Rationale
and verification dose experiment
Each health care product is used
independently in clinical practice;
the SAL of an individual health
Number of identical health care Single health care product taken care product within the packaging
products in their packaging system from the packaging system system meets the selected SAL,
although the overall SAL associated
with the packaging system can be
higher.
Kit of procedure-related health care Each type of health care product Each health care product is used
products a comprising the kit independently in clinical practice.
a In dose establishment, the sterilization dose is chosen based on the health care product requiring the highest
sterilization dose.
5.1.2 If the product has a claim of sterility for part of the product, the sterilization dose may be
established on the basis of that part only.
EXAMPLE If the product has a label claim of sterility for the fluid path only, the sterilization dose may be
established based on bioburden determinations and outcomes of tests of sterility performed on the fluid path.
5.2 Sample item portion (SIP)
5.2.1 For product with an average bioburden greater than or equal to 1,0, whenever practicable, an
entire product (SIP equal to 1,0) should be used for testing according to Table 1. When the use of an entire
product is not practicable, a sample item portion (SIP) of product may be substituted. The SIP should be
as large a portion of the item as practicable and should be of a size that can be handled during testing.
5.2.2 For a product with an average bioburden less than 1,0, an entire product (SIP equal to 1,0) shall
be used for testing in accordance with Table 1.
NOTE When testing products with low average bioburden, it is possible that an SIP will not always be the
portion of the product item possessing microorganisms. Therefore, the entire product (SIP = 1,0) is used for
products with an average bioburden less than 1,0.
5.2.3 If the bioburden is evenly distributed either on the item or in the item, or both, the SIP may
be selected from any portion of the item. If the bioburden is not evenly distributed, the SIP shall
consist of either
a) portions of product selected at random that proportionally represent each of the materials from
which the product is made, or
b) the portion of the product that is considered to be the most severe challenge to the
sterilization process.
The value of SIP can be calculated on the basis of length, mass, volume or surface area (see Table 2
for examples).
Table 2 — Examples for calculation of SIP

Basis for SIP Product
Tubing (consistent diameter)
Length
Rolls of bandage
Powders
Mass
Gowns
Volume Liquids

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Basis for SIP Product

Surgical drapes
Surface area
Tubing (variable diameter)
For bulk type materials, a representative sample may be considered as an SIP of 1,0 for the product (i.e.
powder, gels and liquids). The rationale for the selected sample size should be documented.
5.2.4 The preparation and packaging of an SIP shall be carried out under conditions that minimize
alterations to bioburden. Environmentally-controlled conditions should be used for preparation of SIPs
and, whenever possible, packaging materials should be equivalent to those used for the finished product.
5.2.5 The adequacy of a selected SIP shall be demonstrated. The bioburden of the SIP shall be such
that either at least 17 of the 20 non-irradiated SIPs yield positive tests of sterility, or a bioburden of one
or more is found on at least 85 % of 20 or more SIPs. If neither of these criteria is met, an SIP that is
different than that examined originally and that meets one of the above criteria shall be used. If an entire
product is tested (SIP equal to 1,0), the criteria specified above do not apply.
NOTE When performing a bioburden determination on bulk materials such as powder, gels and liquids
(see ISO 11737‑1:2018, B.3.3), it is not necessary to demonstrate the adequacy of the SIP used in the bioburden
determination.
5.2.6 The same SIP should be used in the performance of tests of sterility when carrying out the
verification dose experiment as that used in the determination of bioburden when obtaining the
verification dose.
If the SIP used in the performance of tests of sterility is different from that used in the determination of
bioburden, caution should be exercised when selecting the sterilization dose and when calculating the
value of SIP VDmaxSD. In carrying out these two activities, two separate determinations of bioburden
are required: one for the SIP used to obtain the bioburden for the entire product item employed in the
selection of the sterilization dose and the other for the SIP used to obtain the value of SIP VDmaxSD
employed in the performance of the verification dose experiment.
5.3 Manner of sampling
5.3.1 Product for sterilization dose substantiation and for sterilization dose auditing shall be
representative of that subjected to routine manufacturing procedures and conditions.
5.3.2 Each product item used in the determination of bioburden or in the performance of a test of
sterility should be taken, where applicable (see Table 1), from a separate packaging system.
5.3.3 For product capable of supporting microbial growth, the maximum allowable amount of time from
manufacture to sterilization of product shall be determined. Storage conditions (including refrigeration
of product, if applicable) should be considered as part of this determination. The period of time between
the taking of product items from production and the determination of bioburden or the performance of
the verification dose experiment should be reflective of the maximum allowable holding time.
The manufacturing step to use in this determination of the maximum allowable holding time should be
the last step before the product would be capable of supporting microbial growth (e.g. the last mixing
step for a liquid formulation), and in many cases this might not be the very last manufacturing step
prior to sterilization of product.
5.3.4 Product items may be selected from product rejected during the manufacturing process provided
that they have been subjected to the same manufacturing procedures and conditions as the remainder of
production, including packaging.

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5.4 Microbiological testing
5.4.1 Bioburden determinations and performance of tests of sterility shall be conducted in accordance
with ISO 11737‑1 and ISO 11737‑2, respectively.
To reduce the possibility of false positives in carrying out tests of sterility, items may be disassembled
and repackaged prior to irradiation. Manipulations prior to irradiation shall not change the magnitude
of the bioburden or its response to radiation (i.e. manipulations that alter the chemical environment in
the vicinity of the microorganisms, typically oxygen tension).
5.4.2 Bioburden determinations shall be carried out on product that has undergone the
packaging process.
NOTE Generally, it is sufficient to perform a bioburden determination on a product item after removal from
its packaging system and to omit the packaging system from the determination.
5.5 Irradiation
5.5.1 Irradiation of product in performing sterilization dose substantiation and sterilization dose
auditing shall be conducted in an irradiator that has undergone installation qualification and operational
qualification in accordance with ISO 11137‑1.
5.5.2 Measurement of dose and the use of radiation sources shall be in accordance with ISO 11137‑1.
5.5.3 For the performance of a verification dose experiment, sufficient performance qualification dose
mapping shall be carried out to identify the highest and the lowest doses delivered to product.
5.5.4 Whenever practicable, for the performance of a verification dose experiment, product should be
irradiated in its original form and in its packaging system.
5.5.5 Materials for repackaging product items for irradiation, if applicable (see 5.4.1), shall be capable
of withstanding the doses delivered and subsequent handling, thereby minimizing the likelihood of
contamination.
NOTE See ISO 11137‑3 for guidance on dosimetric aspects of radiation sterilization.
6 Method VD max SD — 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
6.1 Rationale
Operationally, the method of substantiation for a selected sterilization dose is similar to dose setting
Method 1 of ISO 11137‑2; it too requires a determination of bioburden and the performance of a
verification dose experiment.
In carrying out substantiation, the method verifies that bioburden present on product prior to
sterilization is less resistant to radiation than a microbial population of maximal resistance consistent
with the attainment of an SAL of 10−6 at the selected sterilization dose; verification is conducted
through performance of a verification dose experiment at an SAL of 10−1 using 10 product items. The
dose at an SAL of 10−1 for a population having this resistance (maximal verification dose, VDmax) is
characteristic of the bioburden level, the sterilization dose and the associated maximal resistance. In
establishing the maximal resistance for a particular bioburden level and sterilization dose, due account
has been taken of the various resistance components of the SDR, the latter being the basis of Method
1. Components of the SDR of high resistance that have significant effect on the attainment of an SAL of
10−6 have been used to define the maximal resistances on which this substantiation method is based.

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In this way, the level of conservativeness of the SDR, and thus of Method 1, is preserved. See Kowalski
and Tallentire[7]; Kowalski, Aoshuang, and Tallentire[8]; Kowalski and Tallentire[11].
In practice, a determination is made of the average bioburden. Based on this average value, a sterilization
dose is selected from a table listing the upper limits of average bioburden that apply to specified selected
sterilization doses. These upper limits are the numbers of microorganisms possessing a given maximal
resistance commensurate with the attainment of a SAL of 10−6 at the selected sterilization dose. The
VDmax dose corresponding to the selected sterilization dose and the average bioburden is read from a
second table; it is the dose at which the verification dose experiment is carried out. Ten product items,
or portions thereof (if applicable, see 5.2), are exposed to the VDmaxSD dose and each item is subjected
individually to a test of sterility. If there is no more than one positive test of sterility in the 10 tests, the
pre-selected sterilization dose is substantiated.
The VDmax methods given in this document are for selected sterilization doses of 17,5 kGy, 20 kGy,
22,5 kGy, 27,5 kGy, 30 kGy, 32,5 kGy and 35 kGy. To distinguish these applications of Method VDmax
and their associated sets of values of verification dose, a superscript has been added to the term VDmax
where appropriate, i.e.. VDmaxSD, where SD is the selected sterilization dose.
NOTE Inspection of the values of the VDmax SD for the various levels of average bioburden given in each of
the tables in Clause 8 reveals a change in the relationship between the bioburden level and the value of VDmax SD.
With increasing bioburden up to a certain level, values progressively increase, as can be expected. However, at
a particular bioburden level, the VDmax SD takes a maximum, and for higher bioburden levels, the corresponding
VDmax SD values progressively decrease. For example, for Method VDmax17,5, VDmax17,5 values progressively
increase up to a bioburden level of 2,5. However, at a bioburden of 2,5, the value of VDmax17,5 takes a maximum,
and for higher bioburden levels, the corresponding VDmax17,5 values decrease. A similar increase, followed by a
decrease, is seen with the other VDmax SD methods. This behaviour is not the result of an error in either the tables
or the calculation of the VDmax values. It is an inevitable outcome of building into Method VDmax SD the same
degree of conservativeness as that in Method 1 (see Kowalski and Tallentire[11]).
6.2 Procedure for Method VDmaxSD for multiple production batches
6.2.1 General
6.2.1.1 In applying Method VDmaxSD for product with an average bioburden less than 1,0, the entire
product item shall be used, whereas for product with an average bioburden greater than or equal to 1,0,
an SIP may be used (see 5.2.5).
6.2.1.2 In applying Method VDmaxSD, the six stages below shall be followed.
NOTE For worked examples, see 9.1 and 9.2.
6.2.2 Stage 1: Obtain samples of product
Select 10 product items from each of three independent production batches, in accordance with 5.1, 5.2
(if applicable) and 5.3.
Product will also be needed to perform the verification dose experiment (see 6.2.6.1) and it is possible
that additional product will be needed to validate the adequacy of an SIP less than one (see 5.2.5) or to
perform a confirmatory verification dose experiment (see 6.2.7.2 and 6.2.8).
6.2.3 Stage 2: Determine average bioburden
6.2.3.1 Apply the correction factor in the determination of bioburden (see ISO 11737‑1).
6.2.3.2 Determine the bioburden of each of the selected product items and calculate:
a) the average bioburden per item for each of the three batches of product items (batch
average bioburden);

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b) the average bioburden per item for all selected product items (overall average bioburden).
Bioburden is generally determined on individual product items, but when the bioburden is low (e.g.
less than 10), it is permissible to pool the 10 product items for the determination of average bioburden.
This guidance does not apply to SIP; SIPs should not be pooled, rather a larger SIP should be chosen
(see 5.2.5).
NOTE An observation of no colonies in the determination of bioburden is sometimes expressed as less than
the limit of detection. Use of the limit of detection as a bioburden value in calculating average bioburden can
lead to an overestimation of average bioburden. Overestimation can lead to selection of too high a sterilization
dose and, in consequence, a high value for VDmax SD, thereby affecting the validity of the verification dose
experiment. The use of an approach for bioburden determination having a low limit of detection can reduce such
overestimation (see ISO 11737‑1:2018, A.6.1.1).
For an SIP less than 1,0, calculate the average bioburden for the entire product item (SIP equal to 1,0)
by dividing each of the three SIP batch average bioburdens and the overall SIP average bioburden by
the SIP value.
6.2.4 Stage 3: Obtain the selected sterilization dose
6.2.4.1 In obtaining the selected sterilization dose, values of average bioburden for the entire product
item (SIP equal to 1,0) shall be used (see 6.2.3.2).
6.2.4.2 From Table 3, obtain the selected sterilization dose. In obtaining this dose, all three batch
average bioburdens (SIP equal to 1,0) determined in Stage 2 shall be below or equal to the associated
upper limit of the average bioburden given in Table 3.
6.2.4.3 A sterilization dose greater than the lowest dose consistent with meeting the requirement in
6.2.4.2 may be selected. A rationale for selecting a greater dose can be based on factors such as:
a) the difference between the average bioburden and the upper limit associated with the selected
sterilization dose;
b) available data on the variation in the numbers and types of microorganisms that comprise
the bioburden;
c) available data on the microbiological quality of similar products including the results of sterilization
dose audits;
d) the materials comprising the product and the control of the microbiological quality of materials;
e) the manufacturing process and associated control and monitoring procedures, particularly steps
that affect bioburden or its resistance; and
f) the manufacturing environment, particularly the extent of microbiological control and monitoring,
and available data on the stability of the manufacturing environment over time.
Table 3 — Upper limit of average bioburden for selection of a given sterilization dose
Upper limit for average bioburden Selected sterilization dose
(SIP equal to 1,0) (kGy)
9,0 17,5
45 20
220 22,5
5 000 27,5
23 000 30
100 000 32,5

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Upper limit for average bioburden Selected sterilization dose

(SIP equal to 1,0) (kGy)
440 000 35
6.2.5 Stage 4: Obtain VD max SD
6.2.5.1 From Table 4, identify the table in Clause 8 that gives values of SIP equal to 1,0 VDmaxSD,
SIP dose reduction factor and dose augmentation value, corresponding to different values of average
bioburden, for the selected sterilization dose.
Table 4 — Table in Clause 8 corresponding to the selected sterilization dose

Selected sterilization dose Corresponding table in
(kGy) Clause 8
17,5 Table 5
20 Table 6
22,5 Table 7
27,5 Table 8
30 Table 9
32,5 Table 10
35 Table 11
6.2.5.2 Compare the three batch average bioburdens to the overall average bioburden found in Stage
2 and determine whether any one of the batch average bioburdens is two or more times greater than the
overall average bioburden.
6.2.5.3 From the identified table in Clause 8, obtain the value of SIP equal to 1,0 VDmaxSD using one of
the following as the average bioburden:
a) if a batch average bioburden is two or more times greater than the overall average bioburden, use
the highest batch average bioburden, or
b) if each of the batch average bioburdens is less than two times the overall average bioburden, use
the overall average bioburden.
For an SIP equal to 1,0, if the average bioburden is not given in the identified table in Clause 8, use
the closest tabulated value greater than the average bioburden to locate the value of SIP equal to
1,0 VDmaxSD.
For an SIP less than 1,0, use the average bioburden for the entire product item (SIP equal to 1,0),
calculated in Stage 2 (6.2.3.2), to enter the identified table in Clause 8. If the calculated average
bioburden is not given in the identified table in Clause 8, use the closest tabulated value greater than
the average bioburden to locate the value of SIP equal to 1,0 VDmaxSD and the corresponding SIP dose
reduction factor. Use Formula (1) to calculate the SIP VDmaxSD (see Kowalski and Tallentire[11]).
SIP VDmaxSD = (SIP equal to 1,0 VDmaxSD) + (SIP dose reduction factor × log SIP) (1)
Use of an SIP less than 1,0 is not permitted for product with an average bioburden less than 1,0
(see 6.2.1.1).
6.2.6 Stage 5: Perform verification dose experiment
6.2.6.1 Select 10 product items from a single batch of product. The 10 product items for the
performance of Stage 5 may be selected from one of the batches on which a bioburden determination

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was carried out in Stage 2, or from a fourth batch manufactured under conditions that are representative
of normal production (see 5.3).
6.2.6.2 Irradiate these product items at VDmaxSD obtained from the identified table in Clause 8 or
calculated using Formula (1), whichever is appropriate.
The highest dose to product items shall not exceed VDmaxSD by more than 10 % or 0,1 kGy,
whichever is greater.
A tolerance of 0,1 kGy is allowed in order to accommodate the ability and practicality of irradiation
facilities to deliver and measure VDmaxSD doses below 1,0 kGy.
The arithmetic mean of the highest and lowest doses to product items should not be less than
90 % of VDmaxSD.
Determine the dose delivered (see 5.5).
If the highest dose to product items exceeds VDmaxSD by more than 10 % or 0,1 kGy, whichever is
greater, the verification dose experiment shall be repeated.
If the arithmetic mean of the highest and lowest doses to product items is less than 90 % of VDmaxSD,
the verification dose experiment may be repeated. If this mean dose is less than 90 % of VDmaxSD and,
on performance of tests of sterility, acceptable results are observed (see 6.2.7), the verification dose
experiment need not be repeated.
6.2.6.3 Subject each irradiated product item individually to a test of sterility (see 5.4.1) and record the
number of positive tests of sterility.
6.2.7 Stage 6: Interpretation of results
6.2.7.1 If no more than one positive test of sterility is obtained from the 10 tests carried out, accept
verification and thereby substantiate the selected sterilization dose.
6.2.7.2 If two positive tests of sterility are obtained, perform a confirmatory verification dose
experiment (see 6.2.8).
6.2.7.3 If three or more positive tests of sterility are obtained, do not accept verification as the selected
sterilization dose can be inadequate.
If the occurrence of these positive tests of sterility can be ascribed to incorrect performance of the
determination of bioburden, incorrect performance of tests of sterility or incorrect delivery of
VDmaxSD or a specific bioburden-related cause, implement corrective action and repeat the verification
dose experiment using a further 10 product items from a batch manufactured under conditions
that are representative of normal production. If, as a result of corrective action, the estimate of
average bioburden changes, for the repeat verification dose experiment use the VDmaxSD (6.2.5) that
corresponds to the changed average bioburden. If the estimate of average bioburden is unchanged, use
the same VDmaxSD as that used in the verification dose experiment that was not accepted. Interpret the
results of the repeat verification dose experiment in accordance with 6.2.7.
If the occurrence of these positive tests of sterility cannot be ascribed to incorrect performance of the
determination of bioburden, incorrect performance of tests of sterility or incorrect delivery of VDmaxSD
or a specific bioburden-related cause, the selected sterilization dose is not substantiated and another
approach for establishing a sterilization dose shall be used. Other approaches are:
a) selection and substantiation of a higher sterilization dose than that for which verification was not
accepted using Method VDmaxSD, starting at Stage 3 (6.2.4);
b) Method 1;

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c) Method 2; and
d) a method providing assurance, in regard to achieving maximally an SAL of 10−6, equivalent to that
of other methods of dose establishment.
6.2.8 Confirmatory verification dose experiment
6.2.8.1 General
If a confirmatory verification dose experiment is to be carried out (see 6.2.7.2), the three stages below
shall be followed.
6.2.8.2 Stage 1: Obtain samples of product
Select 10 product items from a single batch of product. The 10 product items for the performance of
the confirmatory verification dose experiment may be selected from one of the batches on which a
bioburden determination was carried out in Stage 2 (see 6.2.3), from the fourth batch used in Stage 5
(see 6.2.6.1) or from a batch manufactured under conditions that are representative of normal
production (see 5.3).
6.2.8.3 Stage 2: Perform confirmatory verification dose experiment
6.2.8.3.1 Irradiate these product items at VDmaxSD obtained in 6.2.5.
The arithmetic mean of the highest and lowest doses to product items should not be less than 90 %
of VDmaxSD .
If the arithmetic mean of the highest and lowest doses to product items is less than 90 % of VDmaxSD
, the confirmatory verification dose experiment may be repeated. If this mean dose is less than 90 %
of VDmaxSD and, on performance of tests of sterility, acceptable results are observed (see 6.2.8.4), the
confirmatory verification dose experiment need not be repeated.
6.2.8.3.2 Subject each irradiated product item individually to a test of sterility (see 5.4.1) and record
the number of positive tests of sterility.
6.2.8.4 Stage 3: Interpretation of results
6.2.8.4.1 If there are no positive tests of sterility from the 10 tests carried out, accept confirmatory
6.2.8.4.2 If any positive tests of sterility are obtained, do not accept confirmatory verification as the
selected sterilization dose can be inadequate.
If the occurrence of these positive tests of sterility can be ascribed to incorrect performance of tests of
sterility or incorrect delivery of VDmaxSD, or a specific bioburden-related cause, implement corrective
action and repeat the confirmatory verification dose experiment using a further 10 product items from
a batch manufactured under conditions that are representative of normal production and the same

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VD max SD as that used originally. Interpret the results of the repeat confirmatory verification dose
experiment in accordance with 6.2.8.4.
If the occurrence of these positive tests of sterility cannot be ascribed to incorrect performance of
tests of sterility or incorrect delivery of VDmaxSD, or a specific bioburden-related cause, the selected
sterilization dose is not substantiated and another approach for establishing a sterilization dose shall
be used. Other approaches are:
b) Method 1;
c) Method 2; and
6.3 Procedure for Method VDmaxSD for a single production batch
6.3.1 Rationale
This method is an adaptation of Method VDmaxSD and is intended to be used only for the substantiation
of a selected sterilization dose for a single production batch.
6.3.2 General
6.3.2.1 In applying Method VDmaxSD for product with an average bioburden less than 1,0, the entire
product item shall be used, whereas for product with an average bioburden greater than 0,9, an SIP may
be used (see 5.2.5).
6.3.2.2 Product capable of supporting microbial growth should be stored under conditions that inhibit
such growth for the time between manufacture of the single production batch and sterilization.
6.3.2.3 In applying Method VDmaxSD, the six stages below shall be followed.
6.3.3 Stage 1: Obtain samples of product
Select 10 product items from the single production batch, in accordance with 5.1, 5.2 (if
applicable) and 5.3.
Product will also be needed to perform the verification dose experiment (see 6.3.7) and additional
product can be needed to validate the adequacy of an SIP less than one (see 5.2.5) or to perform a
confirmatory verification dose experiment (see 6.3.9).
6.3.4 Stage 2: Determine average bioburden
6.3.4.1 Apply the correction factor in the determination of bioburden (see ISO 11737‑1).
6.3.4.2 Determine the bioburden of each of the selected product items and calculate the
average bioburden.

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(see 5.2.5).
NOTE An observation of no colonies in the determination of bioburden is sometimes expressed as less than
lead to an overestimation of average bioburden. Overestimation can lead to selection of too high a sterilization
dose and, in consequence, a high value of VDmax SD, thereby affecting the validity of the verification dose
experiment. The use of an approach for bioburden determination having a low limit of detection can reduce such
overestimation (see ISO 11737‑1:2018, A.6.1.1).
For an SIP less than 1,0, calculate the average bioburden for the entire product item (SIP equal to 1,0) by
dividing the SIP batch average bioburden by the SIP value.
6.3.5 Stage 3: Obtain the selected sterilization dose
6.3.5.1 In obtaining the selected sterilization dose, the value of average bioburden for the entire
product item (SIP equal to 1,0) shall be used (see 6.3.4.2).
6.3.5.2 From Table 3, obtain the selected sterilization dose. In obtaining this dose, the batch average
bioburden (SIP equal to 1,0) determined in Stage 2 shall be less than or equal to the associated upper
limit of the average bioburden given in Table 3.
6.3.5.3 A sterilization dose greater than the lowest dose consistent with meeting the requirement in
6.3.5.2 may be selected. A rationale for selecting a greater dose can be based on factors such as:
a) the difference between the average bioburden and the upper limit associated with the selected
sterilization dose;
b) available data on the variation in the numbers and types of microorganisms that comprise
the bioburden;
c) available data on the microbiological quality of similar products including the results of sterilization
dose audits;
d) the materials comprising the product and the control of the microbiological quality of materials;
e) the manufacturing process and associated control and monitoring procedures, particularly steps
that affect bioburden or its resistance; and
f) the manufacturing environment, particularly the extent of microbiological control and monitoring,
and available data on the stability of the manufacturing environment over time.
6.3.6 Stage 4: Obtain VDmaxSD
6.3.6.1 From Table 4, identify the table in Clause 8 that gives the values of SIP equal to 1,0 VDmaxSD,
SIP dose reduction factor and dose augmentation value, corresponding to different values of average
bioburden, for the selected sterilization dose.
6.3.6.2 From the identified table, obtain the value of SIP equal to 1,0 VDmaxSD using the average
bioburden for the entire product item (SIP equal to 1,0).
For an SIP equal to 1,0, if the average bioburden is not given in the identified table in Clause 8, use
the closest tabulated value greater than the average bioburden to locate the value of SIP equal to
1,0 VDmaxSD.
For an SIP less than 1,0, use the average bioburden for the entire product item (SIP equal to 1,0),
calculated in Stage 2 (6.3.4.2), to enter the identified table in Clause 8. If the calculated average bioburden
is not given in the table, use the closest tabulated value greater than the average value to locate the

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value of SIP equal to 1,0 VDmaxSD and corresponding SIP dose reduction factor. Use Formula (1) (see
6.2.5.3) to calculate the SIP VDmaxSD (see Kowalski and Tallentire[11]).
NOTE Use of an SIP less than 1,0 is not permitted for product with an average bioburden less than 1,0
(see 6.3.2.1).
6.3.7 Stage 5: Perform verification dose experiment
6.3.7.1 Select 10 product items from the single batch of product.
6.3.7.2 Irradiate these product items at VDmaxSD obtained from the identified table in Clause 8 or
derived using Formula (1), whichever is appropriate.
90 % of VDmaxSD.
on performance of tests of sterility, acceptable results are observed (see 6.3.8), the verification dose
6.3.7.3 Subject each irradiated product item individually to a test of sterility (see 5.4.1) and record the
number of positive tests of sterility.
6.3.8 Stage 6: Interpretation of results
6.3.8.1 If no more than one positive test of sterility is obtained from the 10 tests carried out, accept
6.3.8.2 If two positive tests of sterility are obtained, perform a confirmatory verification dose
experiment (see 6.3.9).
6.3.8.3 If three or more positive tests of sterility are obtained, do not accept verification as the selected
If the occurrence of these positive tests of sterility can be ascribed to incorrect performance of the
or a specific bioburden-related cause, implement corrective action and repeat the verification dose
experiment using a further 10 product items. If, as a result of corrective action, the estimate of average
bioburden changes, use the VDmaxSD (6.3.6) that corresponds to the changed average bioburden. If the
estimate of average bioburden is unchanged, use the same VDmaxSD as that used in the verification dose
experiment that was not accepted. Interpret the results of the repeat verification dose experiment in
accordance with 6.3.8.
If the occurrence of these positive tests of sterility cannot be ascribed to incorrect performance of the

BS ISO 13004:2022
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or a specific bioburden-related cause, the selected sterilization dose is not substantiated and another
approach for establishing a sterilization dose shall be used. Other approaches are:
b) Method 1;
c) Method 2; and
6.3.9 Confirmatory verification dose experiment
6.3.9.1 General
If a confirmatory verification dose experiment is to be carried out (see 6.3.8.2), the three stages below
shall be followed.
Select 10 product items from the single production batch of product.
6.3.9.3 Stage 2: Perform confirmatory verification dose experiment
6.3.9.3.1 Irradiate these product items at VDmaxSD obtained in 6.3.6.
90 % of VDmaxSD.
greater, the confirmatory verification dose experiment shall be repeated.
the confirmatory verification dose experiment may be repeated. If this mean dose is less than 90 %
of VDmaxSD and, on performance of tests of sterility, acceptable results are observed (see 6.3.9.4), the
6.3.9.3.2 Subject each irradiated product item individually to a test of sterility (see 5.4.1) and record
the number of positive tests of sterility.
6.3.9.4.1 If there are no positive tests of sterility from the 10 tests carried out, accept confirmatory

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6.3.9.4.2 If any positive tests of sterility are obtained, do not accept verification as the selected
action and repeat the confirmatory verification dose experiment using a further 10 product items and
the same VDmaxSD as that used originally. Interpret the results of the repeat confirmatory verification
dose experiment in accordance with 6.3.9.4.
tests of sterility or incorrect delivery of VDmaxSD, or a specific bioburden-related cause, the selected
sterilization dose is not substantiated and another approach for establishing a sterilization dose shall
be used. Other approaches are:
b) Method 1;
c) Method 2; and
7 Maintaining process effectiveness
7.1 General
For product produced as multiple production batches, periodic determinations of bioburden and
sterilization dose audits are carried out to confirm the continued effectiveness of the established
sterilization dose. Requirements for maintaining process effectiveness given in ISO 11137‑1:2006,
Clause 12 apply to a selected sterilization dose substantiated using Method VDmaxSD. None of these
requirements apply to product produced as a single production batch.
7.2 Frequency of determination of bioburden

Follow requirements in ISO 11137‑1.
7.3 Sterilization dose audit
7.3.1 Frequency
The frequency at which sterilization dose audits are carried out shall be in accordance with
ISO 11137‑1:2006, 12.1. Sterilization dose audits are not required during periods in which product is
not produced. A review of environmental and manufacturing controls, together with determinations of
bioburden, should be conducted in conjunction with sterilization dose audits. If the review indicates
lack of control, appropriate action shall be taken.
7.3.2 Outcome
Actions resulting from the outcome of a sterilization dose audit shall apply to all product comprising
the product family (see Clause 4).

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7.3.3 Procedure for auditing a sterilization dose substantiated using Method VDmaxSD
7.3.3.1 General
7.3.3.1.1 For the performance of a sterilization dose audit for a selected sterilization dose,
substantiated using Method VDmaxSD, use an SIP equivalent to that used originally in substantiating the
sterilization dose.
7.3.3.1.2 In applying the sterilization dose audit, the four stages below shall be followed.
NOTE For a worked example, see 9.3.
Select 20 product items from a single batch of product, in accordance with 5.1, 5.2 (if applicable) and 5.3.
7.3.3.3 Stage 2: Determine average bioburden
7.3.3.3.1 Apply the correction factor found from the most recent validation of the method of bioburden
determination.
7.3.3.3.2 Determine the bioburden of each of 10 product items and calculate the average bioburden.
(see 5.2.5).
NOTE 1 An observation of no colonies in the determination of bioburden is sometimes expressed as less than
lead to overestimation of the average. The use of an approach for bioburden determination having a low limit of
detection can reduce such overestimation.
NOTE 2 These bioburden data are not intended to be used in obtaining the value of SIP equal to 1,0 VDmax SD for
the sterilization dose audit. They are used for process monitoring and control (e.g. trend analysis), investigation
of sterilization dose audit failure and obtaining the dose augmentation value. The adjustment of the verification
dose is not appropriate with each bioburden study; however, for a sustained shift in magnitude of the bioburden,
dose re-establishment can substantiate the sterilization dose (see ISO 11137‑1).
7.3.3.4 Stage 3: Perform verification dose experiment
7.3.3.4.1 Irradiate 10 product items at VDmaxSD used in the most recent successful substantiation of
the selected sterilization dose.
90 % of VDmaxSD.

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on performance of tests of sterility, acceptable results are observed (see 7.3.3.5), the verification dose
7.3.3.4.2 Subject each irradiated product item individually to a test of sterility (see 5.4.1) using the
media and incubation conditions used in the original dose substantiation. Record the number of positive
tests of sterility.
7.3.3.5.1 If no more than one positive test of sterility is obtained from the 10 tests carried out, accept
the sterilization dose audit.
7.3.3.5.2 If two positive tests of sterility are obtained, perform a confirmatory sterilization dose audit
(see 7.3.3.6).
7.3.3.5.3 If three or more positive tests of sterility are obtained, do not accept the sterilization dose
audit as the selected sterilization dose can be inadequate.
action and repeat the verification dose experiment as soon as practicable using a further 10 product
items from a batch manufactured under conditions that are representative of normal production and
the same VDmaxSD as that used in the sterilization dose audit that was not accepted. Interpret the
results of the repeat verification dose experiment in accordance with 7.3.3.5.
tests of sterility or incorrect delivery of VDmaxSD, or a specific bioburden-related cause, the following
shall apply.
a) If three to six positive tests of sterility are obtained, augment the selected sterilization dose
immediately (see 7.3.3.7) and re-establish the sterilization dose as soon as practicable using
another approach. Other approaches are:
1) selection and substantiation of a higher sterilization dose than that for which verification was
not accepted using Method VDmaxSD, starting at Stage 1 (6.2.2 or 6.3.3, as appropriate);
2) Method 1;
3) Method 2; and
4) a method providing assurance, in regard to achieving maximally an SAL of 10−6, equivalent to
that of other methods of dose establishment.
Continue to use the augmented sterilization dose until re-establishment of the sterilization dose
is completed.
b) If seven or more positive tests of sterility are obtained, discontinue sterilization at the selected
sterilization dose. Do not augment the selected sterilization dose and do not resume sterilization
until the sterilization dose is re-established using another approach. Other approaches are:
1) selection and substantiation of a higher sterilization dose than that for which verification was
not accepted using Method VDmaxSD, starting at Stage 1 (6.2.2 or 6.3.3, as appropriate);
2) Method 1;
3) Method 2; and

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7.3.3.6 Confirmatory sterilization dose audit
7.3.3.6.1 General
7.3.3.6.1.1 For the performance of a confirmatory sterilization dose audit for a selected sterilization
dose, substantiated using Method VDmaxSD, use an SIP equivalent to that used originally in substantiating
the sterilization dose.
7.3.3.6.1.2 In applying the confirmatory sterilization dose audit, the three stages below shall
be followed.
7.3.3.6.2 Stage 1: Obtain samples of product
Select 10 product items from a single batch of product, in accordance with 5.1, 5.2 (if applicable) and
5.3. The 10 product items for the performance of confirmatory sterilization dose audit may be selected
from either the batch used for the verification dose experiment carried out in the original sterilization
dose audit (see 7.3.3) or a second batch manufactured under conditions that are representative of
normal production (see 5.3).
7.3.3.6.3 Stage 2: Perform confirmatory verification dose experiment
7.3.3.6.3.1 Irradiate 10 product items at VDmaxSD used in the most recent successful substantiation of
the selected sterilization dose.
The arithmetic mean of the highest and lowest doses to product items should not be less
than 90 % of VD max SD .
greater, the confirmatory verification dose experiment shall be repeated.
the confirmatory verification dose experiment may be repeated. If this mean dose is less than 90 % of
VDmaxSD and, on performance of tests of sterility, acceptable results are observed (see 7.3.3.6.4), the
7.3.3.6.3.2 Subject each irradiated product item individually to a test of sterility (see 5.4.1) using the
media and incubation conditions used originally in the substantiation of the selected sterilization dose
and record the number of positive tests of sterility.
7.3.3.6.4 Stage 3: Interpretation of results
Interpret the results of the confirmatory verification dose audit performed in accordance with
7.3.3.6, as follows:
a) If there are no positive tests of sterility from the 10 tests carried out, accept the
sterilization dose audit.

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b) If one to four positive tests of sterility are obtained, do not accept the sterilization dose audit.
Augment the selected sterilization dose immediately (see 7.3.3.7) and re-establish the sterilization
dose as soon as practicable using another approach. Other approaches are:
1) selection and substantiation of a higher sterilization dose than that for which the sterilization
dose audit was not accepted, starting at Stage 1 (6.2.2 or 6.3.3, as appropriate);
2) Method 1;
3) Method 2; and
Continue to use the augmented sterilization dose until re-establishment of the sterilization dose
is completed.
c) If five or more positive tests of sterility are obtained, do not accept the sterilization dose audit.
Discontinue sterilization at the selected sterilization dose. Do not augment the selected sterilization
dose and do not resume sterilization until the sterilization dose is re-established using another
approach. Other approaches are:
1) selection and substantiation of a higher sterilization dose than that for which the sterilization
dose audit was not accepted, starting at Stage 1 (6.2.2 or 6.3.3, as appropriate);
2) Method 1;
3) Method 2; and
If the occurrence of one or more positive tests of sterility can be ascribed to incorrect performance
of tests of sterility or incorrect delivery of VDmaxSD, or a specific bioburden-related cause, implement
corrective action and repeat the confirmatory sterilization dose audit (see 7.3.3.6) using a further
10 product items from a batch manufactured under conditions that are representative of normal
production and the same VDmaxSD as that used in the original sterilization dose substantiation.
Interpret the results, in accordance with a) to c) above.
7.3.3.7 Augmentation of a sterilization dose substantiated using Method VDmaxSD
From the previously identified table in Clause 8 (see Table 4) for the selected sterilization dose, obtain
the dose augmentation value corresponding to the average bioburden (SIP equal to 1,0) as determined
in accordance with 7.3.3.3. If the average bioburden is not given in the table, use the closest tabulated
value greater than the average bioburden to obtain the dose augmentation value. The augmented
sterilization dose is the sum of the selected sterilization dose and the dose augmentation value.
7.3.4 Failure of a sterilization dose audit
Following failure of a sterilization dose audit requiring the re-establishment of the sterilization dose,
the cause of failure shall be investigated and either correction or corrective action, or both, taken in
accordance with ISO 11137‑1:2006, 4.4. As part of the investigation, the effect of irradiating product at
the sterilization dose that has failed sterilization dose audit on the achievement of the specified SAL
for previously irradiated batches of product shall be considered and a risk assessment undertaken on
their suitability for use. The investigation and subsequent actions shall be recorded in accordance with
ISO 11137‑1:2006, 4.1.2.
NOTE It might not be possible to determine the effect of irradiation at the sterilization dose that has failed
the sterilization dose audit on achievement of this SAL until the sterilization dose has been re-established.

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8 Tables of values for SIP

Tables 5 to 11 contain values for SIP equal to 1,0 VDmaxSD, SIP dose reduction factor and augmentation
dose corresponding to applicable values of average bioburden for selected sterilization doses of
17,5 kGy (Table 5), 20 kGy (Table 6), 22,5 kGy (Table 7), 27,5 kGy (Table 8), 30 kGy (Table 9), 32,5 kGy
(Table 10) and 35 kGy (Table 11).
Table 5 — 17,5 kGy selected sterilization dose for which the upper limit of average bioburden
is 9,0
SD = 17,5 kGy
Dose
SIP equal to 1,0 VDmax17,5 SIP
Average bioburden augmentation value
(kGy) dose reduction factor
(kGy)
Less than or equal to 0,1 0,0 NAa 3,5
0,15 0,6 NAa 3,4
0,20 1,0 NAa 3,3
0,25 1,3 NAa 3,2
0,30 1,5 NAa 3,2
0,35 1,7 NAa 3,2
0,40 1,9 NAa 3,1
0,45 2,0 NAa 3,1
0,50 2,1 NAa 3,1
0,60 2,4 NAa 3,0
0,70 2,5 NAa 3,0
0,80 2,7 NAa 3,0
0,90 2,8 NAa 2,9
1,0 2,9 2,92 2,9
1,5 3,3 2,83 2,8
2,0 3,6 2,78 2,8
2,5 3,8 2,74 2,7
3,0 3,7 2,50 2,8
3,5 3,6 2,32 2,8
4,0 3,5 2,17 2,8
4,5 3,4 2,05 2,8
5,0 3,3 1,95 2,8
5,5 3,3 1,87 2,9
6,0 3,2 1,79 2,9
6,5 3,1 1,73 2,9
7,0 3,1 1,67 2,9
7,5 3,0 1,62 2,9
8,0 3,0 1,57 2,9
8,5 3,0 1,53 2,9
9,0 2,9 1,49 2,9
a Not applicable: SIP equal to 1,0 required; see 6.2.1.1 and 6.3.2.1.

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Table 6 — 20 kGy selected sterilization dose for which the upper limit of average bioburden
is 45
SD = 20 kGy
Dose
SIP equal to 1,0 VDmax20 SIP
(kGy)
less than or equal to 0,1 0,0 NAa 4,0
0,15 0,7 NAa 3,9
0,20 1,1 NAa 3,8
0,25 1,5 NAa 3,7
0,30 1,7 NAa 3,7
0,35 2,0 NAa 3,6
0,40 2,1 NAa 3,6
0,45 2,3 NAa 3,5
0,50 2,5 NAa 3,5
0,60 2,7 NAa 3,5
0,70 2,9 NAa 3,4
0,80 3,1 NAa 3,4
0,90 3,2 NAa 3,4
1,0 3,3 3,33 3,3
1,5 3,8 3,24 3,2
2,0 4,1 3,17 3,2
2,5 4,4 3,13 3,1
3,0 4,6 3,09 3,1
3,5 4,7 3,06 3,1
4,0 4,9 3,03 3,0
4,5 5,0 3,01 3,0
5,0 5,1 2,99 3,0
5,5 5,2 2,97 3,0
6,0 5,2 2,95 3,0
6,5 5,3 2,94 2,9
7,0 5,4 2,92 2,9
7,5 5,5 2,91 2,9
8,0 5,5 2,88 2,9
8,5 5,5 2,82 2,9
9,0 5,4 2,77 2,9
9,5 5,4 2,72 2,9
10 5,3 2,67 2,9
11 5,3 2,58 2,9
12 5,2 2,51 3,0
13 5,2 2,44 3,0
14 5,1 2,39 3,0
15 5,1 2,33 3,0
16 5,0 2,28 3,0
17 5,0 2,24 3,0

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SD = 20 kGy
Dose
(kGy)
18 5,0 2,20 3,0
19 4,9 2,16 3,0
20 4,9 2,13 3,0
21 4,9 2,10 3,0
22 4,8 2,07 3,0
23 4,8 2,04 3,0
24 4,8 2,01 3,0
25 4,8 1,99 3,0
26 4,8 1,97 3,1
27 4,7 1,94 3,1
28 4,7 1,92 3,1
29 4,7 1,90 3,1
30 4,7 1,89 3,1
31 4,7 1,87 3,1
32 4,6 1,85 3,1
33 4,6 1,83 3,1
34 4,6 1,81 3,1
35 4,6 1,80 3,1
36 4,6 1,78 3,1
37 4,6 1,77 3,1
38 4,5 1,76 3,1
39 4,5 1,74 3,1
40 4,5 1,73 3,1
41 4,5 1,72 3,1
42 4,5 1,71 3,1
43 4,5 1,70 3,1
44 4,5 1,68 3,1
45 4,4 1,67 3,1
is 220
SD = 22,5 kGy
Dose
(kGy)
0,15 0,8 NAa 4,3
0,20 1,3 NAa 4,2
0,25 1,7 NAa 4,2
0,30 2,0 NAa 4,1
0,35 2,2 NAa 4,1

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SD = 22,5 kGy
Dose
(kGy)
0,40 2,4 NAa 4,0
0,45 2,6 NAa 4,0
0,50 2,8 NAa 3,9
0,60 3,0 NAa 3,9
0,70 3,3 NAa 3,8
0,80 3,4 NAa 3,8
0,90 3,6 NAa 3,8
1,0 3,8 3,75 3,8
1,5 4,3 3,64 3,6
2,0 4,6 3,57 3,6
2,5 4,9 3,52 3,5
3,0 5,1 3,47 3,5
3,5 5,3 3,44 3,4
4,0 5,5 3,41 3,4
4,5 5,6 3,38 3,4
5,0 5,7 3,36 3,4
5,5 5,8 3,34 3,3
6,0 5,9 3,32 3,3
6,5 6,0 3,30 3,3
7,0 6,1 3,29 3,3
7,5 6,1 3,27 3,3
8,0 6,2 3,26 3,3
8,5 6,3 3,25 3,2
9,0 6,3 3,24 3,2
9,5 6,4 3,22 3,2
10 6,4 3,21 3,2
11 6,5 3,20 3,2
12 6,6 3,18 3,2
13 6,7 3,16 3,2
14 6,8 3,15 3,1
15 6,8 3,14 3,1
16 6,9 3,12 3,1
17 6,9 3,11 3,1
18 7,0 3,10 3,1
19 7,0 3,09 3,1
20 7,1 3,08 3,1
21 7,1 3,07 3,1
22 7,2 3,06 3,1
23 7,2 3,06 3,1
24 7,3 3,05 3,0
25 7,3 3,03 3,0

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SD = 22,5 kGy
Dose
(kGy)
26 7,3 3,00 3,1
27 7,2 2,97 3,1
28 7,2 2,94 3,1
29 7,2 2,92 3,1
30 7,2 2,89 3,1
31 7,2 2,87 3,1
32 7,1 2,85 3,1
33 7,1 2,82 3,1
34 7,1 2,80 3,1
35 7,1 2,78 3,1
36 7,1 2,74 3,1
37 7,1 2,74 3,1
38 7,0 2,73 3,1
39 7,0 2,71 3,1
40 7,0 2,69 3,1
41 7,0 2,68 3,1
42 7,0 2,66 3,1
43 7,0 2,65 3,1
44 7,0 2,63 3,1
45 6,9 2,62 3,1
46 6,9 2,60 3,1
47 6,9 2,59 3,1
48 6,9 2,58 3,1
49 6,9 2,56 3,1
50 6,9 2,55 3,1
55 6,8 2,50 3,1
60 6,8 2,44 3,1
65 6,8 2,40 3,2
70 6,7 2,36 3,2
75 6,7 2,32 3,2
80 6,7 2,29 3,2
85 6,6 2,26 3,2
90 6,6 2,23 3,2
95 6,6 2,21 3,2
100 6,5 2,18 3,2
110 6,5 2,14 3,2
120 6,5 2,09 3,2
130 6,4 2,06 3,2
140 6,4 2,03 3,2
150 6,4 2,00 3,2
160 6,3 1,98 3,2

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SD = 22,5 kGy
Dose
(kGy)
170 6,3 1,95 3,2
180 6,3 1,93 3,2
190 6,2 1,90 3,3
200 6,2 1,88 3,3
220 6,2 1,85 3,3
is 5 000
SD = 27,5 kGy
Dose
SIP equal to 1,0 VDmax27,5 SIP augmentation value
Average bioburden
(kGy)
0,15 0,9 NAa 5,3
0,20 1,6 NAa 5,2
0,25 2,0 NAa 5,1
0,30 2,4 NAa 5,0
0,35 2,7 NAa 5,0
0,40 3,0 NAa 4,9
0,45 3,2 NAa 4,9
0,50 3,4 NAa 4,8
0,60 3,7 NAa 4,8
0,70 4,0 NAa 4,7
0,80 4,2 NAa 4,7
0,90 4,4 NAa 4,6
1,0 4,6 4,58 4,6
2,0 5,7 4,36 4,4
3,0 6,3 4,25 4,2
4,0 6,7 4,17 4,2
5,0 7,0 4,11 4,1
6,0 7,2 4,06 4,1
7,0 7,4 4,02 4,0
8,0 7,6 3,98 4,0
9,0 7,7 3,95 4,0
10 7,9 3,93 3,9
11 8,0 3,91 3,9
12 8,1 3,88 3,9
13 8,2 3,87 3,9
14 8,3 3,85 3,8
15 8,3 3,83 3,8
16 8,4 3,82 3,8

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SD = 27,5 kGy
Dose
Average bioburden
(kGy)
17 8,5 3,80 3,8
18 8,5 3,79 3,8
19 8,6 3,78 3,8
20 8,7 3,77 3,8
21 8,7 3,76 3,8
22 8,8 3,75 3,7
23 8,8 3,74 3,7
24 8,9 3,73 3,7
25 8,9 3,72 3,7
26 9,0 3,71 3,7
27 9,0 3,70 3,7
28 9,0 3,69 3,7
29 9,1 3,69 3,7
30 9,1 3,68 3,7
31 9,1 3,67 3,7
32 9,2 3,66 3,7
33 9,2 3,66 3,7
34 9,2 3,65 3,7
35 9,3 3,65 3,6
36 9,3 3,64 3,6
37 9,3 3,63 3,6
38 9,4 3,63 3,6
39 9,4 3,62 3,6
40 9,4 3,62 3,6
41 9,4 3,61 3,6
42 9,5 3,61 3,6
43 9,5 3,60 3,6
44 9,5 3,60 3,6
45 9,5 3,59 3,6
46 9,6 3,59 3,6
47 9,6 3,58 3,6
48 9,6 3,58 3,6
49 9,6 3,58 3,6
50 9,6 3,57 3,6
55 9,7 3,55 3,6
60 9,8 3,54 3,5
65 9,9 3,52 3,5
70 10,0 3,51 3,5
75 10,0 3,49 3,5
80 10,1 3,48 3,5
85 10,2 3,47 3,5

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SD = 27,5 kGy
Dose
Average bioburden
(kGy)
90 10,2 3,46 3,5
95 10,3 3,45 3,4
100 10,3 3,44 3,4
110 10,4 3,42 3,4
120 10,5 3,40 3,4
130 10,6 3,39 3,4
140 10,6 3,38 3,4
150 10,7 3,36 3,4
160 10,7 3,35 3,4
170 10,8 3,34 3,3
180 10,8 3,33 3,3
190 10,9 3,32 3,3
200 10,9 3,31 3,3
220 11,0 3,30 3,3
240 11,1 3,28 3,3
260 11,1 3,26 3,3
280 11,1 3,21 3,3
300 11,1 3,18 3,3
325 11,0 3,14 3,3
350 11,0 3,10 3,3
375 11,0 3,07 3,3
400 10,9 3,04 3,3
425 10,9 3,01 3,3
450 10,9 2,98 3,3
475 10,9 2,96 3,3
500 10,9 2,93 3,3
525 10,8 2,91 3,3
550 10,8 2,89 3,3
575 10,8 2,87 3,3
600 10,8 2,85 3,3
650 10,8 2,82 3,4
700 10,7 2,79 3,4
750 10,7 2,76 3,4
800 10,7 2,73 3,4
850 10,7 2,71 3,4
900 10,6 2,69 3,4
950 10,6 2,67 3,4
1 000 10,6 2,65 3,4
1 050 10,6 2,63 3,4
1 100 10,6 2,61 3,4
1 150 10,6 2,60 3,4

BS ISO 13004:2022
ISO 13004:2022

SD = 27,5 kGy
Dose
Average bioburden
(kGy)
1 200 10,5 2,58 3,4
1 250 10,5 2,57 3,4
1 300 10,5 2,55 3,4
1 350 10,5 2,54 3,4
1 400 10,5 2,53 3,4
1 450 10,5 2,51 3,4
1 500 10,5 2,50 3,4
1 550 10,4 2,49 3,4
1 600 10,4 2,48 3,4
1 650 10,4 2,47 3,4
1 700 10,4 2,46 3,4
1 750 10,4 2,45 3,4
1 800 10,4 2,44 3,4
1 850 10,4 2,43 3,4
1 900 10,4 2,42 3,4
1 950 10,4 2,41 3,4
2 000 10,4 2,41 3,4
2 100 10,3 2,39 3,4
2 200 10,3 2,37 3,4
2 300 10,3 2,36 3,4
2 400 10,3 2,35 3,4
2 500 10,3 2,34 3,4
2 600 10,3 2,32 3,4
2 700 10,3 2,31 3,5
2 800 10,2 2,30 3,5
2 900 10,2 2,29 3,5
3 000 10,2 2,28 3,5
3 200 10,2 2,26 3,5
3 400 10,2 2,24 3,5
3 600 10,2 2,23 3,5
3 800 10,1 2,21 3,5
4 000 10,1 2,20 3,5
4 200 10,1 2,19 3,5
4 400 10,1 2,17 3,5
4 600 10,1 2,16 3,5
4 800 10,1 2,15 3,5
5 000 10,1 2,14 3,5

BS ISO 13004:2022
ISO 13004:2022

is 23 000
SD = 30 kGy
Dose
(kGy)
0,15 1,0 NAa 5,8
0,20 1,7 NAa 5,7
0,25 2,2 NAa 5,6
0,30 2,6 NAa 5,5
0,35 2,9 NAa 5,4
0,40 3,2 NAa 5,4
0,45 3,5 NAa 5,3
0,50 3,7 NAa 5,3
0,60 4,0 NAa 5,2
0,70 4,3 NAa 5,1
0,80 4,6 NAa 5,1
0,90 4,8 NAa 5,0
1,0 5,0 5,00 5,0
2,0 6,2 4,76 4,8
3,0 6,8 4,63 4,6
4,0 7,3 4,54 4,5
5,0 7,6 4,48 4,5
6,0 7,9 4,43 4,4
7,0 8,1 4,38 4,4
8,0 8,3 4,35 4,3
9,0 8,4 4,31 4,3
10 8,6 4,29 4,3
11 8,7 4,26 4,3
12 8,8 4,24 4,2
13 8,9 4,22 4,2
14 9,0 4,20 4,2
15 9,1 4,18 4,2
16 9,2 4,16 4,2
17 9,3 4,15 4,1
18 9,3 4,13 4,1
19 9,4 4,12 4,1
20 9,5 4,11 4,1
21 9,5 4,10 4,1
22 9,6 4,09 4,1
23 9,6 4,08 4,1
24 9,7 4,06 4,1
25 9,7 4,06 4,1
26 9,8 4,05 4,0

BS ISO 13004:2022
ISO 13004:2022

SD = 30 kGy
Dose
(kGy)
27 9,8 4,04 4,0
28 9,9 4,03 4,0
29 9,9 4,02 4,0
30 9,9 4,01 4,0
31 10,0 4,00 4,0
32 10,0 4,00 4,0
33 10,0 3,99 4,0
34 10,1 3,98 4,0
35 10,1 3,98 4,0
36 10,1 3,97 4,0
37 10,2 3,96 4,0
38 10,2 3,96 4,0
39 10,2 3,95 4,0
40 10,3 3,95 3,9
41 10,3 3,94 3,9
42 10,3 3,94 3,9
43 10,3 3,93 3,9
44 10,4 3,92 3,9
45 10,4 3,92 3,9
46 10,4 3,92 3,9
47 10,4 3,91 3,9
48 10,5 3,91 3,9
49 10,5 3,90 3,9
50 10,5 3,90 3,9
55 10,6 3,88 3,9
60 10,7 3,86 3,9
65 10,8 3,84 3,8
70 10,9 3,82 3,8
75 11,0 3,81 3,8
80 11,0 3,80 3,8
85 11,1 3,78 3,8
90 11,1 3,77 3,8
95 11,2 3,76 3,8
100 11,3 3,75 3,8
110 11,3 3,73 3,7
120 11,4 3,71 3,7
130 11,5 3,70 3,7
140 11,6 3,68 3,7
150 11,7 3,67 3,7
160 11,7 3,66 3,7
170 11,8 3,65 3,6

BS ISO 13004:2022
ISO 13004:2022

SD = 30 kGy
Dose
(kGy)
180 11,8 3,63 3,6
190 11,9 3,62 3,6
200 11,9 3,61 3,6
220 12,0 3,60 3,6
240 12,1 3,58 3,6
260 12,2 3,57 3,6
280 12,2 3,55 3,6
300 12,3 3,54 3,5
325 12,4 3,52 3,5
350 12,4 3,51 3,5
375 12,5 3,50 3,5
400 12,6 3,49 3,5
425 12,6 3,48 3,5
450 12,7 3,47 3,5
475 12,7 3,46 3,5
500 12,8 3,45 3,4
525 12,8 3,44 3,4
550 12,8 3,43 3,4
575 12,9 3,42 3,4
600 12,9 3,42 3,4
650 13,0 3,40 3,4
700 13,0 3,39 3,4
750 13,1 3,38 3,4
800 13,2 3,37 3,4
850 13,2 3,35 3,4
900 13,1 3,32 3,4
950 13,1 3,30 3,4
1 000 13,1 3,27 3,4
1 050 13,1 3,25 3,4
1 100 13,1 3,23 3,4
1 150 13,0 3,21 3,4
1 200 13,0 3,19 3,4
1 250 13,0 3,18 3,4
1 300 13,0 3,16 3,4
1 350 13,0 3,14 3,4
1 400 13,0 3,13 3,4
1 450 13,0 3,11 3,4
1 500 13,0 3,10 3,4
1 550 12,9 3,09 3,4
1 600 12,9 3,07 3,4
1 650 12,9 3,06 3,4

BS ISO 13004:2022
ISO 13004:2022

SD = 30 kGy
Dose
(kGy)
1 700 12,9 3,05 3,4
1 750 12,9 3,04 3,4
1 800 12,9 3,03 3,4
1 850 12,9 3,02 3,4
1 900 12,9 3,01 3,4
1 950 12,9 3,00 3,4
2 000 12,9 2,99 3,4
2 100 12,8 2,97 3,4
2 200 12,8 2,95 3,4
2 300 12,8 2,93 3,4
2 400 12,8 2,92 3,4
2 500 12,8 2,90 3,4
2 600 12,8 2,89 3,4
2 700 12,8 2,88 3,5
2 800 12,7 2,86 3,5
2 900 12,7 2,85 3,5
3 000 12,7 2,84 3,5
3 200 12,7 2,82 3,5
3 400 12,7 2,80 3,5
3 600 12,7 2,78 3,5
3 800 12,6 2,76 3,5
4 000 12,6 2,74 3,5
4 200 12,6 2,73 3,5
4 400 12,6 2,71 3,5
4 600 12,6 2,70 3,5
4 800 12,6 2,69 3,5
5 000 12,6 2,67 3,5
5 300 12,5 2,65 3,5
5 600 12,5 2,63 3,5
5 900 12,5 2,62 3,5
6 200 12,5 2,61 3,5
6 500 12,5 2,59 3,5
6 800 12,5 2,58 3,5
7 100 12,4 2,56 3,5
7 400 12,4 2,55 3,5
7 700 12,4 2,54 3,5
8 000 12,4 2,53 3,5
8 500 12,4 2,52 3,5
9 000 12,4 2,50 3,5
9 500 12,4 2,48 3,5
10 000 12,4 2,47 3,5

BS ISO 13004:2022
ISO 13004:2022

SD = 30 kGy
Dose
(kGy)
10 500 12,3 2,46 3,5
11 000 12,3 2,44 3,5
11 500 12,3 2,43 3,5
12 000 12,3 2,42 3,5
13 000 12,3 2,40 3,5
14 000 12,3 2,38 3,6
15 000 12,2 2,36 3,6
16 000 12,2 2,35 3,6
17 000 12,2 2,33 3,6
18 000 12,2 2,32 3,6
19 000 12,2 2,31 3,6
20 000 12,2 2,29 3,6
21 000 12,1 2,28 3,6
22 000 12,1 2,27 3,6
23 000 12,1 2,26 3,6
is 100 000
SD = 32,5 kGy
Dose
(kGy)
0,15 1,1 NAa 6,3
0,20 1,8 NAa 6,1
0,25 2,4 NAa 6,0
0,30 2,8 NAa 5,9
0,35 3,2 NAa 5,9
0,40 3,5 NAa 5,8
0,45 3,8 NAa 5,7
0,50 4,0 NAa 5,7
0,60 4,4 NAa 5,6
0,70 4,7 NAa 5,6
0,80 5,0 NAa 5,5
0,90 5,2 NAa 5,5
1,0 5,4 5,42 5,4
2,0 6,7 5,16 5,2
3,0 7,4 5,02 5,0
4,0 7,9 4,92 4,9
5,0 8,2 4,85 4,9
6,0 8,5 4,79 4,8

BS ISO 13004:2022
ISO 13004:2022

SD = 32,5 kGy
Dose
(kGy)
7,0 8,8 4,75 4,7
8,0 9,0 4,71 4,7
9,0 9,1 4,67 4,7
10 9,3 4,64 4,6
11 9,4 4,62 4,6
12 9,5 4,59 4,6
13 9,7 4,57 4,6
14 9,8 4,55 4,5
15 9,9 4,53 4,5
16 9,9 4,51 4,5
17 10,0 4,49 4,5
18 10,1 4,48 4,5
19 10,2 4,47 4,5
20 10,2 4,45 4,5
21 10,3 4,44 4,4
22 10,4 4,43 4,4
23 10,4 4,41 4,4
24 10,5 4,40 4,4
25 10,5 4,39 4,4
26 10,6 4,38 4,4
27 10,6 4,37 4,4
28 10,7 4,36 4,4
29 10,7 4,36 4,4
30 10,8 4,35 4,3
31 10,8 4,34 4,3
32 10,8 4,33 4,3
33 10,9 4,32 4,3
34 10,9 4,32 4,3
35 11,0 4,31 4,3
36 11,0 4,30 4,3
37 11,0 4,29 4,3
38 11,1 4,29 4,3
39 11,1 4,28 4,3
40 11,1 4,28 4,3
41 11,2 4,27 4,3
42 11,2 4,26 4,3
43 11,2 4,26 4,3
44 11,2 4,25 4,3
45 11,3 4,25 4,2
46 11,3 4,24 4,2
47 11,3 4,24 4,2

BS ISO 13004:2022
ISO 13004:2022

SD = 32,5 kGy
Dose
(kGy)
48 11,3 4,23 4,2
49 11,4 4,23 4,2
50 11,4 4,22 4,2
55 11,5 4,20 4,2
60 11,6 4,18 4,2
65 11,7 4,16 4,2
70 11,8 4,14 4,1
75 11,9 4,13 4,1
80 11,9 4,11 4,1
85 12,0 4,10 4,1
90 12,1 4,09 4,1
95 12,1 4,07 4,1
100 12,2 4,06 4,1
110 12,3 4,04 4,0
120 12,4 4,02 4,0
130 12,5 4,01 4,0
140 12,6 3,99 4,0
150 12,6 3,98 4,0
160 12,7 3,96 4,0
170 12,8 3,95 3,9
180 12,8 3,94 3,9
190 12,9 3,93 3,9
200 12,9 3,92 3,9
220 13,0 3,90 3,9
240 13,1 3,88 3,9
260 13,2 3,86 3,9
280 13,3 3,85 3,8
300 13,3 3,83 3,8
325 13,4 3,82 3,8
350 13,5 3,80 3,8
375 13,5 3,79 3,8
400 13,6 3,78 3,8
425 13,7 3,77 3,8
450 13,7 3,76 3,8
475 13,8 3,75 3,7
500 13,8 3,74 3,7
525 13,9 3,73 3,7
550 13,9 3,72 3,7
575 13,9 3,71 3,7
600 14,0 3,70 3,7
650 14,1 3,69 3,7

BS ISO 13004:2022
ISO 13004:2022

SD = 32,5 kGy
Dose
(kGy)
700 14,1 3,67 3,7
750 14,2 3,66 3,7
800 14,2 3,65 3,7
850 14,3 3,64 3,6
900 14,4 3,63 3,6
950 14,4 3,62 3,6
1 000 14,4 3,61 3,6
1 050 14,5 3,60 3,6
1 100 14,5 3,59 3,6
1 150 14,6 3,59 3,6
1 200 14,6 3,58 3,6
1 250 14,6 3,57 3,6
1 300 14,7 3,57 3,6
1 350 14,7 3,56 3,6
1 400 14,7 3,55 3,6
1 450 14,8 3,55 3,5
1 500 14,8 3,54 3,5
1 550 14,8 3,54 3,5
1 600 14,8 3,53 3,5
1 650 14,9 3,53 3,5
1 700 14,9 3,52 3,5
1 750 14,9 3,52 3,5
1 800 14,9 3,51 3,5
1 850 15,0 3,51 3,5
1 900 15,0 3,50 3,5
1 950 15,0 3,50 3,5
2 000 15,0 3,49 3,5
2 100 15,1 3,49 3,5
2 200 15,1 3,48 3,5
2 300 15,1 3,47 3,5
2 400 15,2 3,46 3,5
2 500 15,2 3,46 3,5
2 600 15,2 3,45 3,5
2 700 15,3 3,44 3,5
2 800 15,2 3,43 3,5
2 900 15,2 3,41 3,5
3 000 15,2 3,40 3,5
3 200 15,2 3,37 3,5
3 400 15,2 3,35 3,5
3 600 15,2 3,33 3,5
3 800 15,1 3,31 3,5

BS ISO 13004:2022
ISO 13004:2022

SD = 32,5 kGy
Dose
(kGy)
4 000 15,1 3,29 3,5
4 200 15,1 3,27 3,5
4 400 15,1 3,25 3,5
4 600 15,1 3,23 3,5
4 800 15,1 3,22 3,5
5 000 15,1 3,20 3,5
5 300 15,0 3,18 3,5
5 600 15,0 3,16 3,5
5 900 15,0 3,14 3,5
6 200 15,0 3,13 3,5
6 500 15,0 3,11 3,5
6 800 15,0 3,09 3,5
7 100 14,9 3,08 3,5
7 400 14,9 3,07 3,5
7 700 14,9 3,05 3,5
8 000 14,9 3,04 3,5
8 500 14,9 3,02 3,5
9 000 14,9 3,00 3,5
9 500 14,9 2,99 3,5
10 000 14,9 2,97 3,5
10 500 14,8 2,95 3,5
11 000 14,8 2,94 3,5
11 500 14,8 2,93 3,5
12 000 14,8 2,91 3,5
13 000 14,8 2,89 3,5
14 000 14,8 2,87 3,6
15 000 14,7 2,85 3,6
16 000 14,7 2,83 3,6
17 000 14,7 2,81 3,6
18 000 14,7 2,79 3,6
19 000 14,7 2,78 3,6
20 000 14,7 2,76 3,6
21 000 14,6 2,75 3,6
22 000 14,6 2,74 3,6
23 000 14,6 2,73 3,6
24 000 14,6 2,72 3,6
25 000 14,6 2,70 3,6
26 000 14,6 2,69 3,6
27 000 14,6 2,68 3,6
28 000 14,6 2,67 3,6
29 000 14,6 2,66 3,6

BS ISO 13004:2022
ISO 13004:2022

SD = 32,5 kGy
Dose
(kGy)
30 000 14,6 2,66 3,6
32 000 14,5 2,64 3,6
34 000 14,5 2,62 3,6
36 000 14,5 2,61 3,6
38 000 14,5 2,60 3,6
40 000 14,5 2,58 3,6
42 000 14,5 2,57 3,6
44 000 14,5 2,56 3,6
46 000 14,4 2,55 3,6
48 000 14,4 2,54 3,6
50 000 14,4 2,53 3,6
54 000 14,4 2,51 3,6
58 000 14,4 2,50 3,6
62 000 14,4 2,48 3,6
66 000 14,4 2,47 3,6
70 000 14,3 2,45 3,6
75 000 14,3 2,44 3,6
80 000 14,3 2,42 3,6
85 000 14,3 2,41 3,6
90 000 14,3 2,40 3,6
95 000 14,3 2,39 3,6
100 000 14,3 2,38 3,6
is 440 000
SD = 35 kGy
Dose
(kGy)
0,15 1,2 NAa 6,8
0,20 2,0 NAa 6,6
0,25 2,6 NAa 6,5
0,30 3,0 NAa 6,4
0,35 3,4 NAa 6,3
0,40 3,8 NAa 6,2
0,45 4,0 NAa 6,2
0,50 4,3 NAa 6,1
0,60 4,7 NAa 6,1
0,70 5,1 NAa 6,0
0,80 5,4 NAa 5,9

BS ISO 13004:2022
ISO 13004:2022

SD = 35 kGy
Dose
(kGy)
0,90 5,6 NAa 5,9
1,0 5,8 5,83 5,8
2,0 7,2 5,55 5,6
3,0 8,0 5,40 5,4
4,0 8,5 5,30 5,3
5,0 8,9 5,22 5,2
6,0 9,2 5,16 5,2
7,0 9,4 5,11 5,1
8,0 9,6 5,07 5,1
9,0 9,8 5,03 5,0
10 10,0 5,00 5,0
11 10,1 4,97 5,0
12 10,3 4,94 4,9
13 10,4 4,92 4,9
14 10,5 4,90 4,9
15 10,6 4,88 4,9
16 10,7 4,86 4,9
17 10,8 4,84 4,8
18 10,9 4,82 4,8
19 11,0 4,81 4,8
20 11,0 4,79 4,8
21 11,1 4,78 4,8
22 11,2 4,77 4,8
23 11,2 4,75 4,8
24 11,3 4,74 4,7
25 11,3 4,73 4,7
26 11,4 4,72 4,7
27 11,5 4,71 4,7
28 11,5 4,70 4,7
29 11,5 4,69 4,7
30 11,6 4,68 4,7
31 11,6 4,67 4,7
32 11,7 4,66 4,7
33 11,7 4,66 4,7
34 11,8 4,65 4,6
35 11,8 4,64 4,6
36 11,8 4,63 4,6
37 11,9 4,62 4,6
38 11,9 4,62 4,6
39 11,9 4,61 4,6
40 12,0 4,60 4,6

BS ISO 13004:2022
ISO 13004:2022

SD = 35 kGy
Dose
(kGy)
41 12,0 4,60 4,6
42 12,0 4,59 4,6
43 12,1 4,59 4,6
44 12,1 4,58 4,6
45 12,1 4,57 4,6
46 12,2 4,57 4,6
47 12,2 4,56 4,6
48 12,2 4,56 4,6
49 12,2 4,55 4,6
50 12,3 4,55 4,5
55 12,4 4,52 4,5
60 12,5 4,50 4,5
65 12,6 4,48 4,5
70 12,7 4,46 4,5
75 12,8 4,44 4,4
80 12,9 4,43 4,4
85 12,9 4,41 4,4
90 13,0 4,40 4,4
95 13,1 4,39 4,4
100 13,1 4,38 4,4
110 13,2 4,35 4,4
120 13,3 4,33 4,3
130 13,4 4,31 4,3
140 13,5 4,30 4,3
150 13,6 4,28 4,3
160 13,7 4,27 4,3
170 13,7 4,25 4,3
180 13,8 4,24 4,2
190 13,9 4,23 4,2
200 13,9 4,22 4,2
220 14,0 4,20 4,2
240 14,1 4,18 4,2
260 14,2 4,16 4,2
280 14,3 4,14 4,1
300 14,4 4,13 4,1
325 14,4 4,11 4,1
350 14,5 4,10 4,1
375 14,6 4,08 4,1
400 14,7 4,07 4,1
425 14,7 4,06 4,1
450 14,8 4,04 4,0

BS ISO 13004:2022
ISO 13004:2022

SD = 35 kGy
Dose
(kGy)
475 14,8 4,03 4,0
500 14,9 4,02 4,0
525 14,9 4,01 4,0
550 15,0 4,00 4,0
575 15,0 4,00 4,0
600 15,1 3,99 4,0
650 15,1 3,97 4,0
700 15,2 3,96 4,0
750 15,3 3,94 3,9
800 15,3 3,93 3,9
850 15,4 3,92 3,9
900 15,5 3,91 3,9
950 15,5 3,90 3,9
1 000 15,6 3,89 3,9
1 050 15,6 3,88 3,9
1 100 15,6 3,87 3,9
1 150 15,7 3,86 3,9
1 200 15,7 3,85 3,9
1 250 15,8 3,85 3,8
1 300 15,8 3,84 3,8
1 350 15,8 3,83 3,8
1 400 15,9 3,83 3,8
1 450 15,9 3,82 3,8
1 500 15,9 3,81 3,8
1 550 16,0 3,81 3,8
1 600 16,0 3,80 3,8
1 650 16,0 3,80 3,8
1 700 16,0 3,79 3,8
1 750 16,1 3,79 3,8
1 800 16,1 3,78 3,8
1 850 16,1 3,78 3,8
1 900 16,1 3,77 3,8
1 950 16,2 3,77 3,8
2 000 16,2 3,76 3,8
2 100 16,2 3,75 3,8
2 200 16,3 3,75 3,7
2 300 16,3 3,74 3,7
2 400 16,3 3,73 3,7
2 500 16,4 3,72 3,7
2 600 16,4 3,72 3,7
2 700 16,4 3,71 3,7

BS ISO 13004:2022
ISO 13004:2022

SD = 35 kGy
Dose
(kGy)
2 800 16,5 3,70 3,7
2 900 16,5 3,70 3,7
3 000 16,5 3,69 3,7
3 200 16,6 3,68 3,7
3 400 16,6 3,67 3,7
3 600 16,7 3,66 3,7
3 800 16,7 3,65 3,7
4 000 16,8 3,65 3,6
4 200 16,8 3,64 3,6
4 400 16,9 3,63 3,6
4 600 16,9 3,62 3,6
4 800 16,9 3,62 3,6
5 000 17,0 3,61 3,6
5 300 17,0 3,60 3,6
5 600 17,0 3,59 3,6
5 900 17,1 3,58 3,6
6 200 17,1 3,57 3,6
6 500 17,2 3,57 3,6
6 800 17,2 3,56 3,6
7 100 17,2 3,55 3,6
7 400 17,3 3,55 3,5
7 700 17,3 3,54 3,5
8 000 17,3 3,53 3,5
8 500 17,4 3,52 3,5
9 000 17,4 3,51 3,5
9 500 17,4 3,49 3,5
10 000 17,4 3,47 3,5
10 500 17,3 3,45 3,5
11 000 17,3 3,44 3,5
11 500 17,3 3,42 3,5
12 000 17,3 3,41 3,5
13 000 17,3 3,38 3,5
14 000 17,3 3,35 3,6
15 000 17,2 3,33 3,6
16 000 17,2 3,31 3,6
17 000 17,2 3,29 3,6
18 000 17,2 3,27 3,6
19 000 17,2 3,25 3,6
20 000 17,2 3,24 3,6
21 000 17,1 3,22 3,6
22 000 17,1 3,20 3,6

BS ISO 13004:2022
ISO 13004:2022

SD = 35 kGy
Dose
(kGy)
23 000 17,1 3,19 3,6
24 000 17,1 3,18 3,6
25 000 17,1 3,17 3,6
26 000 17,1 3,16 3,6
27 000 17,1 3,14 3,6
28 000 17,1 3,13 3,6
29 000 17,1 3,12 3,6
30 000 17,1 3,11 3,6
32 000 17,0 3,09 3,6
34 000 17,0 3,08 3,6
36 000 17,0 3,06 3,6
38 000 17,0 3,04 3,6
40 000 17,0 3,03 3,6
42 000 17,0 3,02 3,6
44 000 17,0 3,00 3,6
46 000 16,9 2,99 3,6
48 000 16,9 2,98 3,6
50 000 16,9 2,97 3,6
54 000 16,9 2,95 3,6
58 000 16,9 2,93 3,6
62 000 16,9 2,91 3,6
66 000 16,9 2,90 3,6
70 000 16,8 2,88 3,6
75 000 16,8 2,86 3,6
80 000 16,8 2,85 3,6
85 000 16,8 2,83 3,6
90 000 16,8 2,82 3,6
95 000 16,8 2,80 3,6
100 000 16,8 2,79 3,6
110 000 16,7 2,77 3,7
120 000 16,7 2,75 3,7
130 000 16,7 2,73 3,7
140 000 16,7 2,71 3,7
150 000 16,7 2,70 3,7
160 000 16,7 2,68 3,7
170 000 16,6 2,67 3,7
180 000 16,6 2,66 3,7
190 000 16,6 2,65 3,7
200 000 16,6 2,63 3,7
220 000 16,6 2,61 3,7
240 000 16,6 2,60 3,7

BS ISO 13004:2022
ISO 13004:2022

SD = 35 kGy
Dose
(kGy)
260 000 16,5 2,58 3,7
280 000 16,5 2,56 3,7
300 000 16,5 2,55 3,7
320 000 16,5 2,54 3,7
340 000 16,5 2,52 3,7
360 000 16,5 2,51 3,7
380 000 16,5 2,50 3,7
400 000 16,5 2,49 3,7
420 000 16,5 2,48 3,7
440 000 16,4 2,47 3,7
9 Worked examples
9.1 Substantiation of a selected sterilization dose of 17,5 kGy (SIP less than 1,0)
Table 12 shows a worked example for Method VDmax17,5. The example is for a product with multiple
production batches and that was too large for testing so a defined portion of the product item (SIP less
than 1,0) was used.
Table 12 — Method VDmax17,5 substantiation (SIP less than 1,0)

Term Value Comment
Stage 1
SAL 10−6 This method substantiates 17,5 kGy as a sterilization dose to achieve
maximally an SAL of 10−6.
SIP 0,5 The product was too large for the ready performance of tests of sterility;
a 1/2 portion was selected for testing.
Number of 40 Ten from each of three independent batches for bioburden determination
product items plus 10 for the verification dose experiment.
Stage 2
Average 6 The SIP bioburden results from the three batches gave averages of 2, 3
bioburden and 4.
The average bioburden for the entire product item for each of the batches
was calculated:
2/0,5 = 4
3/0,5 = 6
4/0,5 = 8
The overall average bioburden was 6.
The highest batch average bioburden was 8.
The highest batch average bioburden of 8 is less than two times the over-
all average bioburden of 6. Therefore, 6 was used to obtain the SIP equal
to 1,0 VDmax17,5.
Stage 3
Selection of 17,5 kGy All three batch average bioburden values are less than or equal to 9,0, as
sterilization dose is the overall average bioburden.

BS ISO 13004:2022
ISO 13004:2022

Term Value Comment

Stage 4
SIP verification 2,7 kGy Table 5 was used to obtain values of SIP equal to 1,0 VDmax17,5 and SIP
dose dose reduction factor at an average bioburden of 6. The value of SIP
VDmax17,5 dose for an SIP of 0,5 was calculated using Formula (1):
SIP VDmax17,5 =
(SIP equal to 1,0 VDmax17,5) + (SIP dose reduction factor x log SIP)
[Formula (1)]
For the example:
SIP VDmax17,5 = 3,2 kGy + (1,79 kGy x log 0,5) = 2,7 kGy
Stage 5
Verification 2,3 to 2,9 kGy The dose to SIPs in the verification dose experiment ranged from 2,3
dose to 2,9 kGy. The highest dose to product items is less than the calculated
experiment upper limit (3,0 kGy) and the arithmetic mean of the highest and lowest
doses, 2,6 kGy, is not less than 90 % of the verification dose (90 % of
2,7 kGy is 2,4 kGy).
Stage 6
Interpretation 0 positives Doses are within the calculated limits and the results of tests of sterility
of results are acceptable (i.e. less than or equal to one positive); therefore, verifi-
cation was accepted and 17,5 kGy was substantiated as the sterilization
dose.
9.2 Substantiation of a selected sterilization dose of 30 kGy (SIP equal to 1,0)

Table 13 shows a worked example for Method VDmax30. The example is for a product with multiple
production batches and for which the entire product item (SIP equal to 1,0) was used for testing.
Table 13 — Method VDmax30 substantiation (SIP equal to 1,0)

Term Value Comment
Stage 1
SAL 10−6 This method substantiates 30 kGy as a sterilization dose to achieve max-
imally an SAL of 10−6.
SIP 1,0 The entire product was used for testing.
Number of 40 Ten from each of three independent batches for bioburden determination
product items plus 10 for the verification dose experiment.
Stage 2
Average 5 643 The bioburden results from the three batches gave averages of 5 030,
bioburden 5 700, and 6 200.
The highest batch average bioburden is 6 200.
The highest batch average bioburden of 6 200 was less than two times
the overall average bioburden of 5 643. Therefore, the overall average
bioburden of 5 643 was used to obtain the SIP equal to 1,0 VDmax30.
Stage 3
Selection of 30 kGy All three batch average bioburden values are less than or equal to
sterilization dose
23 000, as is the overall average bioburden.
Stage 4
Verification 12,5 kGy An average bioburden of 5 643 is not listed in Table 9 so the next greater
dose bioburden of 5 900 was used to obtain SIP equal to 1,0 VDmax30.
Stage 5

BS ISO 13004:2022
ISO 13004:2022

Term Value Comment

Verification 11,4 to 13,0 kGy The dose to product items in the verification dose experiment ranged
dose from 11,4 to 13,0 kGy. The highest dose to product items is less than the
experiment calculated upper limit (13,8 kGy) and the arithmetic mean of the highest
and lowest doses, 12,2 kGy, is not less than 90 % of the verification dose
(90 % of 12,5 kGy is 11,3 kGy).
Stage 6
Interpretation 0 positives Doses are within the calculated limits and the results of tests of sterility
of results are acceptable (i.e. less than or equal to one positive); therefore, verifi-
cation was accepted and 30 kGy was substantiated as the sterilization
dose.
9.3 Sterilization dose audit for a sterilization dose substantiated using
9.4 Method VDmax22,5

Table 14 shows the findings from a sterilization dose audit performed after a selected sterilization
dose of 22,5 kGy had been substantiated, the findings from which necessitated augmentation of the
sterilization dose.
Table 14 — Sterilization dose audit following which augmentation of the sterilization dose was
required (selected sterilization dose substantiated using Method VDmax22,5)
Term Value Comment
Sterilization dose audit
Stage 1
Number of 20 20 product items were obtained from a single production batch.
product items
Stage 2
SIP 0,5 The original substantiation of 22,5 kGy was conducted using an SIP of 0,5.
SIP average 99 The average bioburden for the 10 SIPs tested was 99.
bioburden
Average 198 The average bioburden for the entire product was calculated as follows: 99/0,5
bioburden = 198
Stage 3
Verification 5,2 to The original substantiation of 22,5 kGy was conducted at a verification dose of
dose 6,0 kGy 5,6 kGy. Ten SIPs were irradiated at this dose. The dose to SIPs in the verifica-
experiment tion dose experiment ranged from 5,2 to 6,0 kGy. The highest dose to SIPs is less
than the calculated upper limit (6,2 kGy) and the arithmetic mean of the highest
and lowest doses, 5,6 kGy, is not less than 90 % of the verification dose (90 % of
5,6 kGy is 5,0 kGy).
Stage 4
Interpretation 2 positives Doses are within the calculated limits but the occurrence of two positive tests
of results of sterility requires that a confirmatory sterilization dose audit be conducted.
Confirmatory sterilization dose audit
Stage 1
Number of 10 Ten product items were obtained from a single production batch.
product items
Stage 2

BS ISO 13004:2022
ISO 13004:2022

Term Value Comment

Confirmatory 5,1 kGy to The verification dose for the confirmatory sterilization dose audit is the same
verification dose 5,9 kGy as the original verification dose. Ten SIPs were irradiated at this dose. The dose
experiment to SIPs in the confirmatory verification dose experiment ranged from 5,1 kGy to
5,9 kGy. The highest dose to SIPs is less than the calculated upper limit (6,2 kGy)
and the arithmetic mean of the highest and lowest doses, 5,5 kGy, is not less
than 90 % of the verification dose (90 % of 5,6 kGy is 5,0 kGy).
Stage 3
Interpretation 1 positive Doses are within the calculated limits but the occurrence of one positive test of
of results sterility requires that the 22,5 kGy sterilization dose be augmented immediate-
ly and that the sterilization dose be re-established using another approach.
Sterilization dose augmentation
Average 198 The average bioburden for the entire product that was determined in perform-
bioburden ing the audit.
Dose 3,3 kGy The average bioburden and Table 7 are used to obtain the dose augmentation
augmentation value. A bioburden of 198 was not listed in the table, so the next greater tabulat-
value ed average bioburden of 200 is used.

BS ISO 13004:2022
ISO 13004:2022

Bibliography
[1] ISO 11137‑2:2013, Sterilization of health care products — Radiation — Part 2: Establishing the
sterilization dose
[2] ISO 11137‑3, Sterilization of health care products — Radiation — Part 3: Guidance on dosimetric
aspects of development, validation and routine control
[3] ISO 11139:2018, Sterilization of health care products — Vocabulary of terms used in sterilization
and related equipment and process standards
[4] NHB 5340.1A, October 1968, The Microbiological Examination of Space Hardware, National
Aeronautics and Space Administration, Washington, DC 20546
[5] Favero M. Microbiologic Assay of Space Hardware. Environ. Biol. Med. 1971, 1 pp. 27–36
[6] Herring C., Brandsberg J., Oxborrow G., Puleo J. Comparison of media for detection of
fungi on spacecraft. Appl. Microbiol. 1974, 27 (3) pp. 566–569
[7] Kowalski J.B., & Tallentire A. Substantiation of 25 kGy as a sterilization dose: A rational
approach to establishing verification dose. Radiat. Phys. Chem. 1999, 54 pp. 55–64
[8] Kowalski J.B., Aoshuang Y., Tallentire A. Radiation sterilization — Evaluation of a new
method for substantiation of 25 kGy. Radiat. Phys. Chem. 2000, 58 pp. 77–86
[9] Kowalski J.B. Field evaluations of the VDmax approach for substantiation of a 25 kGy
sterilization dose and its application to other preselected doses. Radiat. Phys. Chem. 2002,
64 pp. 411–416
[10] Kowalski J.B., & Tallentire A. VDmax — A new method for substantiating 25 kGy. Med.
Device Technol. 2000, 11 pp. 22–25
[11] Kowalski J.B., & Tallentire A. Aspects of putting into practice VDmax. Radiat. Phys. Chem.
2003, 67 pp. 137–141
[12] Kowalski J.B., Patel J., Arscott E., Tallentire A. Computer and field evaluations in support
of Method VDmax15. Radiat. Phys. Chem. 2006, 75 pp. 1107–1112
[13] Kowalski J.B., & Tallentire A. Computer and field evaluations in support of the VDmax
approach for selected doses greater than 25 kGy. Radiat. Phys. Chem. 2010, 79 pp. 1005–1011

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Sterilization of health care products —

Amendments/corrigenda issued since publication

Sterilization of health care products —

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ii ﻿ © ISO 2022 – All rights reserved

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

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Sterilization of health care products — Radiation —

3 Terms and definitions

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[SOURCE: ISO 11139:2018, 3.176, modified — Note 1 to entry was added.]

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[SOURCE: ISO 11139:2018, 3.217]

[SOURCE: ISO 11139:2018, 3.274]

[SOURCE: ISO 11139:2018, 3.275

[SOURCE: ISO 11139:2018, 3.277]

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[SOURCE: ISO 11139:2018, 3.315, modified — Note 1 to entry was added.]

4 Definition and maintenance of product families for sterilization dose

4.2 Defining product families

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a) geographic and/or climatic differences between locations;

4.3 Designation of product to represent a product family

4.3.1 Product to represent a product family

4.3.1.2 A product family shall be represented by:

a) a master product (see 4.3.2), or

a) number of microorganisms comprising the bioburden;

6 ﻿ © ISO 2022 – All rights reserved

4.3.2 Master product

4.3.3 Equivalent product

4.3.4 Simulated product

A simulated product may be:

4.4 Maintaining product families

4.4.1 Periodic review

© ISO 2022 – All rights reserved ﻿ 7

4.4.2 Modification to either product or manufacturing process, or both

4.5 Consequence of failure of sterilization dose substantiation or

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

5.1 Nature of product

5.1.1 Product for sterilization can consist of:

a) an individual health care product in its packaging system;

8 ﻿ © ISO 2022 – All rights reserved

Item for bioburden determination

5.2 Sample item portion (SIP)

Table 2 — Examples for calculation of SIP

© ISO 2022 – All rights reserved ﻿ 9

Basis for SIP Product

5.3 Manner of sampling

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5.4 Microbiological testing

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

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6.2 Procedure for Method VDmaxSD for multiple production batches

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