EN ISO 15882:2008

SLOVENSKI STANDARD
01-november-2008
1DGRPHãþD
SIST EN ISO 15882:2003
Sterilizacija izdelkov za zdravstveno oskrbo - Kemijski indikatorji - Navodilo za
izbiro, uporabo in predstavitev rezultatov (ISO 15882:2008)
Sterilization of health care products - Chemical indicators - Guidance for selection, use
and interpretation of results (ISO 15882:2008)
Sterilisation von Produkten für die Gesundheitsfürsorge - Chemische Indikatoren -
Leitfaden für die Auswahl, Verwendung und Interpretation von Ergebnissen (ISO
15882:2008)
Stérilisation des produits de santé - Indicateurs chimiques - Directives pour la sélection,
l'utilisation et l'interprétation des résultats (ISO 15882:2008)
Ta slovenski standard je istoveten z: EN ISO 15882:2008
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EUROPEAN STANDARD
EN ISO 15882
NORME EUROPÉENNE
EUROPÄISCHE NORM
September 2008
ICS 11.080.01 Supersedes EN ISO 15882:2003
English Version
Sterilization of health care products - Chemical indicators -
Guidance for selection, use and interpretation of results (ISO
15882:2008)
Stérilisation des produits de santé - Indicateurs chimiques - Sterilisation von Produkten für die Gesundheitsfürsorge -
Directives pour la sélection, l'utilisation et l'interprétation Chemische Indikatoren - Leitfaden für die Auswahl,
des résultats (ISO 15882:2008) Verwendung und Interpretation von Ergebnissen (ISO
15882:2008)
This European Standard was approved by CEN on 24 August 2008.
CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European
Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national
standards may be obtained on application to the CEN Management Centre or to any CEN member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by translation
under the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the same status as the
official versions.
CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland,
France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2008 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 15882:2008: E
worldwide for CEN national Members.

Contents Page
Foreword.3

Foreword
This document (EN ISO 15882:2008) has been prepared by Technical Committee ISO/TC 198 "Sterilization of
health care products" in collaboration with Technical Committee CEN/TC 102 “Sterilizers for medical
purposes” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an identical
text or by endorsement, at the latest by March 2009, and conflicting national standards shall be withdrawn at
the latest by March 2009.
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent
rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 15882:2003.
According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Cyprus, Czech
Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia,
Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,
Sweden, Switzerland and the United Kingdom.
Endorsement notice
The text of ISO 15882:2008 has been approved by CEN as a EN ISO 15882:2008 without any modification.

INTERNATIONAL ISO
STANDARD 15882
Second edition
2008-09-01
Sterilization of health care products —
Chemical indicators — Guidance for
selection, use and interpretation of
results
Stérilisation des produits de santé — Indicateurs chimiques —
Directives pour la sélection, l'utilisation et l'interprétation des résultats

Reference number
ISO 15882:2008(E)
©
ISO 2008
ISO 15882:2008(E)
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ii © ISO 2008 – All rights reserved

ISO 15882:2008(E)
Contents Page
Foreword. iv
Introduction . v
1 Scope . 1
2 Terms and definitions. 1
3 General considerations. 3
4 Classes of chemical indicator . 5
4.1 General. 5
4.2 Class 1: Process indicators. 5
4.3 Class 2: Indicators for use in specific tests. 6
4.4 Class 3: Single variable indicators . 6
4.5 Class 4: Multi-variable indicators. 8
4.6 Class 5: Integrating indicators . 8
4.7 Class 6: Emulating indicators . 9
5 Selection of chemical indicators. 10
6 Use of chemical indicators . 10
6.1 Class 1 process indicators . 10
6.2 Class 2 indicators . 11
6.3 Class 3, 4, 5 and 6 indicators. 11
6.4 Indicators for use with process challenge devices. 11
7 Interpretation of results from chemical indicators. 12
7.1 General. 12
7.2 Chemical indicator responses. 12
7.3 Chemical indicators showing “fail” response . 12
8 Chemical indicators in sterility assurance procedures. 12
8.1 General. 12
8.2 Record keeping . 13
9 Personnel training . 13
10 Storage and handling . 14
11 Labelling . 14
11.1 General. 14
11.2 Indicator marking. 14
11.3 Process marking. 14
11.4 Package marking . 14
Annex A (informative) Background on the Bowie and Dick test . 16
Annex B (informative) Explanation of the terms “parameter” and “variable” . 19
Annex C (informative) Rationale for the requirements for integrating indicators and the link to the
requirements for biological indicators (BIs) specified in the ISO 11138 series and
microbial inactivation (derived from ISO 11140-1) . 20
Annex D (informative) Specifications for porosity. 27
Annex E (informative) Figure showing relationship of indicator components. 29
Bibliography . 30

ISO 15882:2008(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies
(ISO member bodies). The work of preparing International Standards is normally carried out through ISO
technical committees. Each member body interested in a subject for which a technical committee has been
established has the right to be represented on that committee. International organizations, governmental and
non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the
International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
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.
ISO 15882 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.
This second edition cancels and replaces the first edition (ISO 15882:2003) which has been technically
revised.
iv © ISO 2008 – All rights reserved

ISO 15882:2008(E)
Introduction
This International Standard provides guidance for users regarding the selection, use and interpretation of
results of chemical indicators intended for use with sterilization processes employing steam, dry heat,
ethylene oxide, γ or β radiation, low temperature steam and formaldehyde (LTSF), or vapourized hydrogen
[13] [12], [13], [14], [15], [16]
peroxide as documented in ISO 11140-1 . The ISO 11140 series of standards specifies
performance requirements for chemical indicators. These standards are intended primarily for the use of
manufacturers of chemical indicators. The guidance in this document is of a general nature; chemical
indicators do not, of themselves, constitute a comprehensive monitoring programme with regard to the
sterilization of health care products. Users' attention is drawn to the requirements for validation of sterilization
[18] [19], [20]
processes specified in ISO 14937 for general processes, the ISO 17665 series for moist heat
[5], [6] [7]
sterilization, the ISO 11135 series for ethylene oxide sterilization, ISO 11137-1 for radiation
[22]
sterilization and ISO 20857 for dry heat sterilization.
The actual use/frequency of chemical indicators might be regulated by international and or national standards
as well as by local regulatory authorities.
The need for convenient and rapid means of detecting sterilization problems occurring during sterilization
processes has brought about the development of sterilization process monitors generally referred to as
“chemical indicators.” In this International Standard, users will find guidance on selection of the correct
chemical indicator for their particular sterilization process and critical parameters as well as guidance on its
appropriate use. The complexity of modern medical technology and the wide variety of sterilization processing
techniques and equipment available have made effective sterility assurance programmes more challenging
than ever before.
INTERNATIONAL STANDARD ISO 15882:2008(E)

Sterilization of health care products — Chemical indicators —
Guidance for selection, use and interpretation of results
1 Scope
1.1 This International Standard provides guidance for the selection, use and interpretation of results
of chemical indicators used in process definition, validation and routine monitoring and overall control
of sterilization processes. This International Standard applies to indicators that show exposure to
sterilization processes by means of physical and/or chemical change of substances, and which are
used to monitor one or more of the variables required of a sterilization process. These chemical
indicators are not dependent for their action on the presence or absence of a living organism.
1.2 This International Standard does not consider indicators for use in those processes that rely on
physical removal of microorganisms, e.g. filtration.
1.3 This International Standard is not intended to apply to indicators for use in combination
processes, for example, washer disinfectors or CIP (cleaning in place) and SIP (sterilization in place).
2 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
[11]
NOTE A vocabulary of terms used for sterilization of health care products is provided in ISO/TS 11139 .
2.1
chemical indicator
non-biological indicator
test system that reveals change in one or more pre-defined process variables based on a chemical or
physical change resulting from exposure to a process
[ISO/TS 11139, definition 2.6]
2.2
endpoint
point of the observed change as defined by the manufacturer occurring after the indicator has been
exposed to specified stated values
[ISO 11140-1, definition 3.3]
2.3
indicator
combination of the indicator agent and its substrate in the final form in which it is intended to be used
[ISO 11140-1 definition 3.5]
NOTE 1 An indicator system in combination with a specific test load is also termed an indicator.
NOTE 2 See Annex E.
ISO 15882:2008(E)
2.4
indicator agent
indicator reagent
active substance(s) or combination of substances
[ISO 11140-1, definition 3.6]
NOTE See Annex E.
2.5
process challenge device
PCD
item designed to constitute a defined resistance to a sterilization process and used to assess
performance of the process
[ISO/TS 11139, definition 2.33]
2.6
process challenge location
PCL
site which represents “worst case” conditions as they are given for sterilizing agent(s) in the goods to
be sterilized
2.7
process parameter
specified value for a process variable
[ISO/TS 11139, definition 2.34]
NOTE 1 The specification for a sterilization process includes the process parameters and their tolerances.
NOTE 2 See Annex B.
2.8
process variable
condition within a sterilization process, changes in which alter microbicidal effectiveness
[ISO/TS 11139, definition 2.35]
EXAMPLES Time, temperature, pressure, concentration, humidity, wavelength.
NOTE See Annex B.
2.9
resistometer
test equipment designed to create defined combinations of the physical and/or chemical parameters of a
sterilization process
2.10
saturated steam
water vapour in a state of equilibrium between condensation and evaporation
[ISO 11140-1 definition 3.11]
2.11
stated value
SV
value or values of a critical variable at which the indicator is designed to reach its endpoint as defined by the
manufacturer
[ISO 11140-1, definition 3.12]
2 © ISO 2008 – All rights reserved

ISO 15882:2008(E)
2.12
visible change
change defined by the manufacturer, which can be seen in the indicator after exposure to one or more critical
variables of the process
NOTE Visible change is used to describe the response of class 1 process indicators.
[ISO 11140-1, definition 3.15]
3 General considerations
3.1 All chemical indicators are intended to provide information about conditions at the location of the
indicator within the sterilizer, sterilizer load or PCD. This can alert the user to potential sterilization process
failures.
3.2 The value of the information provided by a chemical indicator is dependent upon the class of indicator,
number and location of the indicators, being representative of the conditions throughout the sterilizer chamber
or load. Representative locations for a load configuration should be identified during process validation studies.
3.3 The basic performance descriptors of any chemical indicator are its visible change, graduated response
or “endpoint” response. The endpoint response can, for example, involve either the melting of a chemical
substance or a chemical reaction resulting in a specified colour change.
3.4 A number of different classes of chemical indicators have been developed to suit different monitoring
needs and to provide information about the sterilization process. Some types are sensitive to certain specific
problems, such as a failure to attain a required temperature. Others might not respond only to a single
process variable, but might simultaneously respond to several process variables during the sterilization cycle.
Selection of the classes of chemical indicators that are best suited to a particular application should be made
only in the context of:
⎯ What characterizes effective sterilization?
⎯ Which problems could prevent sterilization?
⎯ What are the performance characteristics of the indicator(s)?
⎯ What constitutes effective sterility assurance activities during product release?
Once an indicator is selected, it will be of value in sterility assurance only if it is used and interpreted correctly,
and if the user takes appropriate action in response to the results.
3.5 Chemical indicators of the same class can differ in response characteristics and their means of
[13]
detecting exposure conditions. Chemical indicator classification in ISO 11140-1 is based on defined
performance characteristics (see, e.g., different stated values in that document) rather than on chemical or
physical changes as related to specific sterilization processes. For example, in a steam process, some
indicator types must be exposed to steam for a minimum length of time to achieve the endpoint, some must
be exposed to a minimum temperature, some are affected by a combination of temperature and time of
exposure, and still others are affected by time, temperature and saturated steam. In all cases, the user
compares the response of the chemical indicator to an endpoint described by the manufacturer.
If a chemical indicator fails to reach its endpoint, the facility should follow a documented protocol to investigate
the cause of the problem which could include, but not be limited to, the following items.
a) Was there a sterilizer malfunction that could account for the failure to achieve the endpoint?
b) Has there been a change(s) in the product and/or sterile barrier system?
ISO 15882:2008(E)
c) Has the loading density increased or decreased within the sterile barrier system?
d) Has the sterilization processing container/configuration changed (e.g. number of cartons has increased or
decreased, or the configuration was not the same as that used during validation)?
e) Was sterilizer calibration and/or routine maintenance conducted appropriately?
f) Was the correct sterilizer process chosen for the product sterilized?
g) Was the chemical indicator handled under manufacturer's recommended practices?
h) Have there been changes in the utilities supplied to the sterilizer that could materially affect cycle
execution (pressure, flow rate, non-condensable gases in the steam supply, etc.)?
NOTE For more information, the requirements and guidance provided in the specific process standards,
[20] [22] [7] [24] [25]
ISO/TS 17665-2 , ISO 20857 , ISO 11137-1 , EN 14180 and EN 15424 is valid.
[13]
3.6 Although other factors can influence the efficacy of a sterilization process, ISO 11140-1 identifies the
variables for each sterilization process in Table 1. A specific chemical indicator can respond to one, some, or
all of the variables, as indicated by its class (see Clause 5) and manufacturer's instructions for use.
If the use of the indicator is limited to a specific sterilization cycle, this information is stated or coded on the
product. For example, “STEAM 15 min 121 °C” means that the indicator is for use in a 15 min, 121 °C steam
sterilization cycle. The box around the word “STEAM” signifies that the indicator can only be used in the steam
sterilization process.
Table 1 — Variables for sterilization processes
a
Process Symbol Variables
Steam STEAM Time, temperature and water (as delivered by saturated steam)
Dry heat DRY Time and temperature
Ethylene oxide EO Time, temperature, humidity, and EO concentration
Irradiation IRRAD Total absorbed dose
Low temperature steam and FORM Time, temperature, water (as delivered by saturated steam) and
formaldehyde (LTSF) formaldehyde concentration
Vapourized hydrogen peroxide VH2O2 Time, temperature, hydrogen peroxide concentration, and, if
applicable, plasma
a
These are symbols and are not intended to be translated.
3.7 Class 3, 4, 5 and 6 indicators will have one or more stated value (SV) identified by the manufacturer.
These stated values identify the parameters that the indicator is designed to react to, and the level of
exposure required to achieve the stated visible change, graduated response or endpoint. Details of the SV will
be provided on the indicator, on the indicator packaging, or in information provided with the product. Visible
change is used to describe the response of class 1 process indicators. Graduated response is the progressive
observable change occurring on exposure to one or more process variables allowing assessment of the level
achieved.
The SV's are based on the outcome of tests carried out in a resistometer by a manufacturer.
[21]
The resistometer (ISO 18472 gives further information) is a test vessel that is designed for very rapid
attainment of the particular critical parameters of the sterilization process. These parameters are very closely
controlled during the exposure phase. Because sterilizers typically do not have the same response
4 © ISO 2008 – All rights reserved

ISO 15882:2008(E)
characteristics or accuracy of exposure conditions as found in resistometers, it is very difficult for a user to
replicate manufacturer label claims using a sterilizer. Third party independent laboratories with resistometers
may be used to verify manufacturers' label claims. Since chemical indicators are tested at specific conditions,
inadvertent or intentional exposure to parameters (for example longer time, lower temperature and/or lower
sterilant concentration) outside of those specified by the manufacturer can lead to misleading results.
All chemical indicators in classes 3, 4, 5 and 6 have SV(s) at which they will reach their endpoints. A
sterilization process is defined by a minimum value with an upper limit, e.g. for a moist heat process a
minimum temperature is specified with an upper limit of + 3 °C. The SV(s) of the chemical indicator will
normally be linked to the minimum sterilization parameters for the process employed to process health care
products.
The response of the chemical indicator to a fail condition is verified by exposing the chemical indicators to
conditions lower than the SVs as specified in the accompanying tables.
4 Classes of chemical indicator
4.1 General
[13]
Chemical indicators are classified by their intended use. The chemical indicators described in ISO 11140-1
are classified into six groups. The chemical indicators within each of these classifications are further
subdivided by the sterilization process for which they are designed to be used. The classification structure is
used solely to denote the characteristics and intended use of each type of indicator when used as defined by
the manufacturer. This classification has no hierarchical significance.
Chemical indicators are used to detect whether or not certain critical process variables have reached a
predetermined level in a given sterilization process. The classification denotes the performance characteristics
and intended use of the indicator only.
The performance characteristics of each class enable the respective chemical indicators to convey different
types of information and therefore perform different functions.
All chemical indicators are based on either a chemical and/or physical change that results in a colour change
or in the migration of a chemical.
The following descriptions for each class of chemical indicator will start with an italicized quote taken directly
[13]
from ISO 11140-1 , which has been used to define that specific class of chemical indicator.
4.2 Class 1: Process indicators
Process indicators are intended for use with individual units (e.g. packs, containers) to indicate that the unit
has been directly exposed to the sterilization process, and to distinguish between processed and unprocessed
units. They shall be designed to react to one or more of the critical process variables (ISO 11140-1:2005, 4.2).
This class of indicator is used to identify packs yet to be processed, i.e., identifying packs yet to be processed
versus those processed and ready for distribution if the sterilization cycle ran correctly and if indicators of a
higher class show that the conditions required for sterilization were met. A “pass” response of a class 1
process indicator is not intended to indicate attainment of the conditions required for sterilization.
Process indicators are typically applied to, or visible from, the outside of packages. Examples of process
indicators include indicator tape and packaging material with a chemical indicator printed on it. These
chemical indicators are typically external and exposed directly to the sterilizating agent without the
interference imposed by packaging, and will typically “fail” only when there is gross malfunction. Process
indicators are intended to exhibit a visual change after exposure to what could be a sub-optimal sterilization
cycle.
ISO 15882:2008(E)
[13]
For the irradiation process ISO 11140-1 only describes process indicators for use in γ and β irradiation. For
example, Table 1 from ISO 11140-1:2005, Clause 8 contains the tolerances (upper and lower limits of
performance acceptability for the steam process indicator, when tested by the manufacturer) that need to be
met for each critical parameter. That table is reproduced below.
Table 2 — Test and performance requirements for class 1 process indicators for STEAM
No change or a change that is
Visible change as
markedly different from the visible
Test environment Test time Test temperature specified by the
change as specified by the
manufacturer
manufacturer
Saturated steam 3,0 min ± 5 s 121 °C (+3/0 °C) Acceptable result Unacceptable result
Saturated steam 10,0 min ± 5 s 121 °C (+3/0 °C) Unacceptable result Acceptable result
Saturated steam 0,5 min ± 5 s 134 °C (+3/0 °C) Acceptable result Unacceptable result
Saturated steam 2 min ± 5 s 134 °C (+3/0 °C) Unacceptable result Acceptable result
Dry heat 30 min ± 1 min 140 °C (+2/0 °C) Acceptable result Unacceptable result
NOTE The dry heat test is designed to ensure that process indicators for steam require the presence of steam in order to respond.
4.3 Class 2: Indicators for use in specific tests
Class 2 indicators are intended for use in specific test procedures as defined in relevant sterilizer/sterilization
standards (ISO 11140-1:2005, 4.3).
Chemical indicators widely recognised in class 2 are used to perform the Bowie and Dick-type test. This can
[14]
be carried out using test sheets specified in ISO 11140-3 in combination with the standard textile pack
[23]
specified in EN 285 . Chemical indicators for conducting the alternative Bowie and Dick-type steam
[15]
penetration test are specified in ISO 11140-4 . Chemical indicators for conducting the Bowie and Dick-type
[16]
air removal test are specified in ISO 11140-5 and either used in combination with a standard textile test
pack or alternatively as a ready-to-use pack. Also see Annex A.
The presence of moisture is critical to the effectiveness of the steam sterilization process. The presence of
residual air will impede steam penetration and therefore the presence of moisture on the surfaces to be
sterilized. Class 2 Bowie and Dick-type indicators are intended to demonstrate the rapid and even penetration
of steam and by implication the adequacy of air removal. This condition is generally demonstrated by a
uniform colour change on the indicator sheet. Causes of failure could include the presence of non-
condensable gases in the steam (for example fabric conditioning agents used in the laundering of the textile
pack) or inadequate air removal or air leaks.
Because Bowie and Dick-type indicators are designed to react to a specified exposure that could be different
from those required to achieve effective sterilization, they are not appropriate for use as routine sterilization
cycle indicators. Extending the exposure time for the Bowie and Dick-type test, or disregarding the
manufacturer's recommendations for how to conduct the Bowie and Dick-type test will entirely defeat the
purpose of the test by causing misleading results.
For background information on the Bowie and Dick test, see Annex A.
4.4 Class 3: Single variable indicators
A single variable indicator shall be designed to react to one of the critical variables and is intended to indicate
exposure to a sterilization process at a stated value (SV) of the chosen variable (ISO 11140-1:2005, 4.4).
A single variable indicator is intended to respond to only one critical process variable of the sterilization
process. The variable and its stated value will be provided by the indicator manufacturer and that indicator can
only be used to monitor that process variable.
6 © ISO 2008 – All rights reserved

ISO 15882:2008(E)
For example, a single variable indicator for temperature can only indicate the attainment of a stated value for
temperature, and will not provide reliable information for other process variables such as exposure time or the
presence of steam. The indicator can reveal whether a specific minimum temperature was attained at a
particular location within the sterilizer chamber or the load. The indicator must be correctly selected for the
minimum temperature of the process.
Single variable indicators should be supplemented by other means of monitoring the sterilization process.
Care should be taken when interpreting the results obtained from single variable indicators. Process
parameters (and their tolerances) for chemical indicators share no relationship with process parameters (and
their tolerances) for sterilization processes. Most sterilization processes have more than one process
parameter which must be attained if sterilization is to occur. Table 3 (adopted from Table 7 from ISO 11140-
1:2005) contains tolerances (upper and lower limits of performance acceptability for the chemical indicator,
when tested by the indicator manufacturer) that need to be met for each critical parameter.
The stated values are the predetermined conditions that the manufacturer shall maintain during testing.
Table 3 — Test and performance requirements for class 3 and class 4 indicators
RH
Sterilizing agent
a
Sterilization process Test point Test time Test temperature
concentration mg/l
%
1 SV* + 0 % SV + 0 °C
Steam Not applicable Not applicable
2 SV − 25 % SV − 2 °C
1 SV + 0 % SV + 0 °C
Dry heat Not applicable Not applicable
2 SV − 25 % SV − 5 °C
1 SV + 0 % SV + 0 °C SV + 0 % > 30
Ethylene oxide
2 SV − 25 % SV − 5 °C SV – 25 % > 30
Low temperature steam
1 SV + 0 % SV + 0 °C SV + 0 %
and formaldehyde Not applicable
2 SV − 25 % SV − 3 °C SV − 20 %
(LTSF)
[13]
NOTE For examples of testing multi-variable (class 4) indicators, see 11140-1 .
*SV = Stated value.
a
Test point 1: the indicator, when tested at the SV, shall reach its endpoint.
Test point 2: the indicator, when tested at all SVs minus the combined tolerances, shall not reach its endpoint.
Example
Steam sterilization indicator (class 3: Single variable indicator).
Stated value: 121 °C.
Table 3 provides the test points at which the class 3 indicator must show a “pass” response (test point 1) and a “fail”
[21]
response (test point 2) when tested by the manufacturer using the equipment specified in ISO 18472 .
Test point 1 for this indicator is 121 °C, i.e., the stated value.
Test point 2 for this indicator is (121 °C minus 2 °C), i.e., 119 °C.
Therefore the indicator tested at 121 °C shall give a “pass” response (test point 1) and when tested at 119 °C shall give a
“fail” response (test point 2).
ISO 15882:2008(E)
4.5 Class 4: Multi-variable indicators
A multi-variable indicator shall be designed to react to two or more of the critical variables and is intended to
indicate exposure to a sterilization cycle at stated values (SVs) of the chosen variables (ISO 11140-1:2005,
4.5).
The manufacturer states the conditions under which multi-variable chemical indicators reach their endpoint.
These indicators typically provide more information than either process (class 1) or single variable (class 3)
indicators. Chemical indicators are designed to reach their endpoint when the stated values of the critical
variables have been achieved.
[13]
ISO 11140-1 contains tolerances (upper and lower limits of performance acceptability for the chemical
indicator, when tested by the manufacturer) that need to be met for each critical variable. See Table 3.
An example of multi-variable indicator performance is given below. Although all parameters have been altered
simultaneously in the example, in practice when manufacturers test the indicators, they may vary one or more
parameters while holding the remaining parameters at the stated value.
EXAMPLE Ethylene oxide sterilization indicator (class 4: multi-variable indicator).
Stated values: 60 min at 900 mg/l.
Table 3 provides the tolerances and limiting values (upper and lower limits of performance) for this class 4 indicator. The
tolerances from this table are 60 +0/−25 % min and 900 +0/−25 % mg/l when tested at a relative humidity greater than
30 %. Therefore, the indicator will not reach its endpoint if the time is less than 45 min [i.e., 60 − (60 × 0,25)], the gas
concentration is less than 675 mg/l [i.e., 900 − (900 × 0,25)] and the relative humidity is greater than 30 %. If the time is
60 min or longer, and the EO concentration is 900 mg/l or higher, and the relative humidity is greater than 30 %, the
indicator must reach its endpoint.
An indicator with the above stated values will respond as follows when exposed to the conditions below:
Exposed to the following conditions Based on Table 2 an acceptable indicator
u 44 min at u 650 mg/l must show fail
W 60 min at W 900 mg/l must show pass
In this example, the indicator might not respond to temperature or relative humidity. If temperature and/or relative humidity
have an influence on the indicator performance, the indicator manufacturer should provide this information.
4.6 Class 5: Integrating indicators
Integrating indicators shall be designed to react to all critical variables. The stated values (SVs) are generated
[8][9][10]
to be equivalent to, or exceed the performance requirements given in the ISO 11138 series for BIs
(ISO 11140-1:2005, 4.6). The stated values for steam class 5 integrating indicators are required over the
typical temperature ranges of the steam sterilization process.
Viable microorganisms are affected by all the complex interrelationships of the critical sterilization process
variables. Chemical indicators might not be affected in the same way, but they do provide information about
the specified process variables. This does not necessarily allow accurate assessment of microbial inactivation.
A steam class 5 integrating indicator shall have stated values for time at 135 °C, 121 °C, and at one
temperature between these; the 121 °C stated value for time must be greater than 16,5 min.
A dry heat class 5 integrating indicator shall have stated values for time at 160 °C and 180 °C and an
additional time at either 140 °C or 170 °C.
8 © ISO 2008 – All rights reserved

ISO 15882:2008(E)
An ethylene oxide class 5 integrating indicator shall have stated values for time at 54 °C and 37 °C with
600 mg/l of EO and 60 % RH; the 54 °C stated value shall be greater than 30 min and the 37 °C stated value
shall be greater than 90 min.
An integrating indicator, by definition, will be affected simultaneously by a number of critical process variables.
Because the effects of the critical variables on the integrating indicator are simultaneous, a failure to reach the
“endpoint” might or might not be assignable to a specific variable.
[11]
The performance requirements for a class 5 Integrating indicator are given in ISO 11140-1 .
To understand the rationale for the requirements for class 5 integrating indicators and the link to the
[8][9][10]
and microbial inactivation,
requirements for biological indicators specified in the ISO 11138 series
see Annex C.
4.7 Class 6: Emulating indicators
Emulating indicators are cycle verification indicators which shall be designed to react to all critical variables for
specified sterilization cycles. The stated values (SVs) are generated from the critical variables of the specified
sterilization process (ISO 11140-1:2005, 4.7).
Table 4 — Test and performance requirements for class 6 indicators
Test time RH
Sterilization Gas concentration
a
Test point Test temperature
process mg/l
min %
1 SV* + 0 % SV + 0 °C
Steam Not applicable Not applicable
2 SV − 6 % SV − 1 °C
1 SV + 0 % SV + 0 °C
Dry heat Not applicable Not applicable
2 SV − 20 % SV − 1 °C
1 SV + 0 % SV + 0 °C SV + 0 % > 30
Ethylene oxide
2 SV − 10 % SV − 2 °C SV − 15 % > 30
NOTE For an example of testing emulating (class 6) indicators, see ISO 11140-1:2005, Annex B.

*SV = Stated value.
a
Test point 1: The indicator, when tested at the SV, shall reach its endpoint (pass condition).
Test point 2: The indicator, when tested at all SVs minus the combined tolerances, shall not reach its endpoint (fail condition).
The tolerances defined in Table 4 are the most stringent of the different classes of chemical indicators. These
test conditions can only be achieved in a resistometer and would be virtually impossible to reproduce in a
hospital sterilizer. Emulating indicators can therefore offer a high level of assurance in demonstrating that
critical parameters of a specified cycle have been met. Unless the cycle parameters tested match exactly the
SV stated for an emulating indicator, the results can be seriously erroneous and misleading.
An emulating indicator, by definition, will be affected simultaneously by a number of critical process variables.
...