SIST EN ISO 18472:2006

SLOVENSKI STANDARD
SIST EN ISO 18472:2006
01-julij-2006
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Sterilization of health care products - Biological and chemical indicators - Test equipment
(ISO 18472:2006)
Sterilisation von Produkten für die Gesundheitsfürsorge - Biologische und chemische
Indikatoren - Prüfausrüstung (ISO 18472:2006)
Stérilisation des produits de santé - Indicateurs biologiques et chimiques - Appareillage
d'essai (ISO 18472:2006)
Ta slovenski standard je istoveten z: EN ISO 18472:2006
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 18472:2006 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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EUROPEAN STANDARD
EN ISO 18472
NORME EUROPÉENNE
EUROPÄISCHE NORM
June 2006
ICS 11.080.01

English Version
Sterilization of health care products - Biological and chemical
indicators - Test equipment (ISO 18472:2006)
Stérilisation des produits de santé - Indicateurs biologiques Sterilisation von Produkten für die Gesundheitsfürsorge -
et chimiques - Appareillage d'essai (ISO 18472:2006) Biologische und chemische Indikatoren - Prüfausrüstung
(ISO 18472:2006)
This European Standard was approved by CEN on 19 May 2006.
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 Central Secretariat 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 Central Secretariat has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, 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
© 2006 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 18472:2006: E
worldwide for CEN national Members.

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EN ISO 18472:2006 (E)





Foreword


This document (EN ISO 18472:2006) 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 December 2006, and conflicting national
standards shall be withdrawn at the latest by December 2006.

According to the CEN/CENELEC Internal Regulations, the national standards organizations of
the following countries are bound to implement this European Standard: Austria, Belgium,
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.


Endorsement notice

The text of ISO 18472:2006 has been approved by CEN as EN ISO 18472:2006 without any
modifications.

2

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INTERNATIONAL ISO
STANDARD 18472
First edition
2006-06-01

Sterilization of health care products —
Biological and chemical indicators —
Test equipment
Stérilisation des produits de santé — Indicateurs biologiques et
chimiques — Appareillage d'essai




Reference number
ISO 18472:2006(E)
©
ISO 2006

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ISO 18472:2006(E)
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ii © ISO 2006 – All rights reserved

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ISO 18472:2006(E)
Contents Page
Foreword. iv
Introduction . v
1 Scope. 1
2 Normative references. 1
3 Terms and definitions. 2
4 Performance requirements for resistometers . 4
4.1 Intended use. 4
4.2 Measurement and control capabilities . 4
4.3 Test methods. 4
4.4 Leak test. 4
4.5 Steam resistometer performance requirements. 4
4.6 Ethylene oxide resistometer performance requirements. 7
4.7 Dry heat (heated air) resistometer performance requirements . 9
4.8 Vaporized hydrogen peroxide process resistometer performance requirements. 11
5 Recording systems. 12
5.1 Measurement systems. 12
5.2 Calibration. 12
6 Documentation. 12
6.1 General. 12
6.2 Minimum information . 13
Annex A (informative) Additional performance characterization — Steam . 14
Annex B (informative) Additional performance characterization — Ethylene oxide. 17
Annex C (informative) Additional performance characterization – Dry heat . 20
Annex D (informative) Resistometer documentation and derivations. 22
Bibliography . 28

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ISO 18472:2006(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 18472 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.
This first edition of ISO 18472 partially replaces ISO 11140-2.
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ISO 18472:2006(E)
Introduction
To test the performance of chemical and biological indicators, specific test equipment is required. This
International Standard specifies the performance requirements for the test equipment to be used in order to
establish the response of chemical and biological indicators to critical process variables. This International
Standard does not apply to test equipment for irradiation indicators or low temperature steam and
formaldehyde indicators.
Resistometers constitute test equipment designed to create precise and repeatable sterilizing environments,
allowing the evaluation of their effect on biological inactivation kinetics, chemical reactions, material
degradation and product bioburden. Resistometers allow precise variation of the environmental conditions and
cycle sequences in order to produce controlled physical studies. When used with the defined test methods
given in ISO 11138 for biological indicators and ISO 11140 for chemical indicators, the results of these studies
can be used to demonstrate conformance of biological indicators and chemical indicators to these standards.
Resistometers differ from conventional sterilizers. Instrumentation selection and control requirements for
resistometers are based upon mathematical models in which rates of reaction, measurement accuracy and
process control requirements are evaluated to quantify the effects induced by test equipment-controlled
variables. The requirements for accurate measurement, precise control, and rapid rates of change approach
limits of commercially available process control and calibration instrumentation accuracy. The measurement
and control requirements often prohibit practical validation of a resistometer using procedures that might be
employed in a conventional heat or chemical sterilization system. Resistometers are considered test
equipment rather than sterilizers; therefore, an understanding of instrumentation and process design is critical
in clarifying requirements on precision and accuracy. Practical design has to consider the following:
⎯ achievable measurement and control;
⎯ acceptable equipment induced variation in test results;
⎯ economic design (utilizing tight process controls only where required);
⎯ test method correlation with intended use;
⎯ historical knowledge applied to test procedures and an understanding of micro-environmental physical
phenomena;
⎯ testing and analysis alternatives, when accurate quantitative determinations exceed physical
measurement/control limits.

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INTERNATIONAL STANDARD ISO 18472:2006(E)

Sterilization of health care products — Biological and chemical
indicators — Test equipment
1 Scope
1.1 This International Standard specifies the requirements for test equipment to be used to test chemical
and biological indicators for steam, ethylene oxide, dry heat and vaporized hydrogen peroxide processes for
conformity to the requirements given in ISO 11140-1 for chemical indicators, or the requirements given in the
ISO 11138 series for biological indicators. This International Standard also provides informative methods
useful in characterizing the performance of biological and chemical indicators for intended use and for routine
quality control testing.
ISO 11138-2, ISO 11138-3, ISO 11138-4, and ISO 11140-1 require the use of resistometers specified in this
International Standard, and these resistometers are used in conjunction with the test methods specified in the
appropriate parts of ISO 11138 and ISO 11140.
NOTE Resistometers for formaldehyde indicators are not included in this International Standard. Test methods using
laboratory apparatus for steam-formaldehyde are included in ISO 11138-5, ISO 11140-3 and ISO 11140-4.
1.2 This International Standard does not address the methods used to demonstrate compliance of
biological or chemical indicators to ISO 11138 and ISO 11140, as these are covered in the appropriate parts
of these standards. Indicators used with combination processes, such as washer-disinfection, are not covered
by this International Standard.
NOTE Test equipment and methods necessary for ISO 11140-3, ISO 11140-4 or ISO 11140-5 are specified in those
standards.
1.3 This International Standard does not address safety aspects of the test equipment because these are
usually covered by specific regional, national or local regulations.
2 Normative references
The following referenced documents are indispensable for the application 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 11138-2, Sterilization of health care products — Biological indicators — Part 2: Biological indicators for

ethylene oxide sterilization processes
ISO 11138-3, Sterilization of health care products — Biological indicators — Part 3: Biological indicators for
moist heat sterilization processes
ISO 11138-4, Sterilization of health care products — Biological indicators — Part 4: Biological indicators for
dry heat sterilization processes
ISO 11140-1, Sterilization of health care products —Chemical indicators — Part 1: General requirements
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ISO 18472:2006(E)
1)
ISO 11140-4 , Sterilization of health care products —Chemical indicators — Part 4: Class 2 indicators as an
alternative to Bowie and Dick test for detection of steam penetration
ISO 17665-1, Sterilization of health care products — Moist heat — Part 1: Requirements for the development,
validation and routine control of a sterilization process for medical devices
IEC 60584 (all parts), Thermocouples
IEC 60751:1983, Industrial platinum resistance thermometer sensors
3 Terms and definitions
For the purpose of this document, the terms and definitions given in ISO 11138, ISO 11140 and the following
apply.
3.1
biological indicator
test system containing viable microorganisms providing a defined resistance to a specified sterilization
process
[ISO/TS 11139:2006, definition 2.3]
3.2
calibration
set of operations that establish, under specified conditions, the relationship between values indicated by a
measuring instrument or measuring system, or values represented by a material measure or a reference
material, and the corresponding values realized by standards
[VIM 1993, definition 6.11]
3.3
chemical indicator
non-biological indicator
system that reveals change in one or more predefined process variables based on a chemical or physical
change resulting from exposure to a process
[ISO/TS 11139:2006, definition 2.6]
3.4
come-up period
time elapsed from the introduction of the sterilizing agent to the attainment of the minimum specified exposure
conditions
3.5
come-down period
time elapsed from the termination of the exposure period to an established null reaction point
3.6
exposure period
time from the initial attainment of the minimum specified exposure conditions to the termination of the
exposure period
NOTE This phase of the cycle includes the stabilization period and the steady state period

1) To be published. (Revision of ISO 11140-4:2001)
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ISO 18472:2006(E)
3.7
measurement accuracy
closeness of the agreement between the result of a measurement and the true value of the measurement
NOTE 1 “Accuracy” is a qualitative concept.
NOTE 2 The term “precision” should not be used for “accuracy”.
3.8
null reaction point
terminating set of conditions that are either specified in the document or have been established and
demonstrated to produce no significant effect on the indicators
3.9
precision
degree of reproducibility of a measurement
3.10
reference standard
standard, generally having the highest metrological quality available at a given location or in a given
organization, from which measurements are derived
3.11
resistometer
test equipment designed to create defined combinations of the physical and/or chemical variables of a
sterilization process
NOTE Resistometers were formerly referred to as a Biological Indicator Evaluator Resistometer (BIER) or Chemical
Indicator Evaluator Resistometer (CIER) test systems.
3.12
response time
time required for a 90 % change in sensor output when exposed to a step change in the variable being
measured
NOTE It may be necessary to determine the sensor response time using a faster data sampling rate than the
minimum for the equipment specified in this International Standard. Documentary evidence from the sensor
manufacturer's stated response time is equally acceptable as proof of conformance.
3.13
saturated steam
water vapour in a state of equilibrium between condensation and evaporation
3.14
stabilization period
elapsed time from the attainment of the minimum specified exposure conditions until the end of the defined
time to achieve steady state conditions
3.15
steady state period
that portion of the exposure period which begins after the stabilization period and terminates at the end of the
exposure period, during which time all control parameters are within the specified limits
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ISO 18472:2006(E)
4 Performance requirements for resistometers
4.1 Intended use
The resistometer is intended to be used to expose test samples under stated test conditions, and therefore
shall be capable of producing cycle sequences as required for specific test methods. Depending upon the test
methods defined in ISO 11138-2, ISO 11138-3, ISO 11138-4 and ISO 11140-1, the resistometer utilized need
only verify those limits necessary to characterize the chemical or biological indicators.
NOTE The following specifications define the conditions to be achieved in the vessel in which the sample is to be
placed, but the means by which these conditions are to be controlled are not addressed.
4.2 Measurement and control capabilities
The following performance requirements define the measurement and control capabilities for steam, ethylene
oxide, dry heat, and vaporized hydrogen peroxide resistometers.
4.3 Test methods
The equipment specified in this International Standard shall be used with the detailed test methods given in
the appropriate parts of ISO 11138 and ISO 11140.
NOTE The claimed performance tolerances for chemical and biological indicators are based on the specified
exposure conditions without allowance for the operational tolerances of the test equipment.
4.4 Leak test
4.4.1 With the temperature stabilized and the chamber empty (except for fixed furniture and necessary
monitoring sensors) start the test cycle. When the pressure in the chamber has reached or is below the value
corresponding to the lowest operating vacuum of the test cycle air removal stages, close all the valves
connected to the chamber and stop the vacuum pump. Observe and record the time, t , and the absolute
1
pressure, p . Allow evaporation of condensation in the chamber for 300 s ± 10 s and then observe and record
1
the absolute pressure, p , in the chamber and the time, t . After a further 600 s ± 10 s, again observe and
2 2
record the absolute pressure, p , and the time, t .
3 3
The resistometer may be fitted with a test cycle for air leakage that will carry out this procedure automatically
and display the air leakage in kPa/min (mbar/min).
4.4.2 At the end of the test calculate the rate of pressure rise for the 600 s period.
NOTE 1 If the value of (p − p ) is greater than 2 kPa (20 mbar), this could be due to the initial presence of excessive
2 1
condensate in the sterilizer chamber.
NOTE 2 In a closed vessel at 4 kPa pressure, the pressure changes by approximately 0,1 kPa (1 mbar) for each 10 °C
change in temperature; over the range 20 °C to 140 °C; at 7 kPa (70 mbar) the change is approximately 0,2 kPa (2 mbar).
The test can be compromised if the temperature changes by more than 10 °C during the period in which the chamber
pressure is monitored.
4.5 Steam resistometer performance requirements
4.5.1 Measurement accuracy
The sensors used to measure temperature, vacuum and pressure from within the steam resistometer shall
have a response time as specified in Table 1. The system used to record time, temperature, vacuum and
pressure from within the steam resistometer shall be capable of operation with a resolution and accuracy
within the scale range specified in Table 1.
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ISO 18472:2006(E)
The measurement systems used may operate beyond the scale range specified as long as the limiting values
within the scale range specified in Table 1 are attained.
Requirements shall apply to complete measurement chains including sensors and data processing.
Table 1 — Steam resistometer instrumentation requirements
Sensor
a response time
Measurement Unit Scale range Resolution Accuracy (+/−)
ms
Time HH:MM:SS Selectable 00:00:01 00:00:01 —
Temperature °C 110 to 145 0,1 0,5 u 500
Vacuum kPa 0 to 100 0,1 1,0 u 30
Pressure kPa 100 to 420 0,1 3,5 u 30
a
Accuracy over the test condition range (see 4.1).
4.5.2 Recording interval
The measurement system shall have a recording interval for each of the measurements specified in Table 1 of
not less than one data point per second.
The data may be electronically archived and the print interval can be at the user's discretion.
4.5.3 Process control
The steam resistometer process control shall be capable of producing the conditions given in Table 2.
Table 2 — Steam resistometer physical design/control specifications
Parameter Unit Range Tolerance (+/−)
Time HH:MM:SS Selectable 00:00:01
a
°C 110 to 145 0,5
Temperature
a
Pressure kPa 100 to 420 3,5
Vacuum kPa 3 to 100 1,0
b
Time to achieve vacuum set-point HH:MM:SS u 00:02:00 –
HH:MM:SS u 00:00:10 –
Come-up period
Come-down period HH:MM:SS u 00:00:10 –
Stabilization period u 00:00:10 HH:MM:SS 1,0 °C
a
During steady state period (see Figure 1).
b
Some indicators can be adversely affected by prolonged exposure to dry heat and vacuum. The minimum practicable settings for
evacuation should be used. The time taken should be as consistent as possible in order to minimize potential variability (e.g.,
desiccation can occur).


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ISO 18472:2006(E)

Key
PS stabilization period PNR null reaction point
PSS steady state period SP set point
PE exposure period TS stabilization tolerance
PCU come-up period TSS steady state tolerance
Figure 1 — Stabilization time for temperature for steam resistometer
4.5.4 General steam resistometer requirements
4.5.4.1 The chamber shall be supplied with saturated steam from a source external to the chamber. The
steam supply shall meet the requirements of ISO 11140-4. Means shall be provided to ensure that the test
items are not wetted by entrained water droplets in the steam supply.
4.5.4.2 Air admitted at the end of the cycle shall be filtered through a filter having the capability of
removing not less than 99,5 % of 0,5 µm particles.
4.5.4.3 The sample holder shall allow the indicator to be exposed to the test conditions in the manner
intended by the indicator manufacturer.
The various types of indicator may require customized sample holders. Sample holders might have to be
constructed to hold test items in different vertical and horizontal attitudes to test performance differences.
Consult the indicator manufacturer for guidance when verifying label claim performance.
4.5.5 Air leakage test
When determined by the method given in 4.4, the air leakage rate shall not be greater than
0,13 kPa/min × (54,8/V ) where V is the chamber volume in litres.
c c
4.5.6 Operation of steam resistometer
4.5.6.1 The chamber shall be designed such that the formation of condensate during any stage of the
operating cycle does not affect the required test conditions. In order to avoid excessive condensate formation
during the operating cycle it might be necessary to provide thermostatic control of the inner surfaces of the
resistometer so that they can be maintained at a specified temperature (e.g. the exposure phase temperature).
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ISO 18472:2006(E)
4.5.6.2 Before initiating a test cycle, the inner surface of the chamber shall be heated to the test
temperature.
4.5.6.3 The equipment shall be provided with means to evacuate the chamber to the vacuum set point to
permit adequate air removal prior to admission of steam.
NOTE Steam admission to the chamber should not be used to effect air removal.
4.5.6.4 Temperature and absolute pressure shall be monitored, recorded and verified to be within the
limits required in Table 2 for the selected exposure conditions as given in ISO 11138-3 or ISO 11140-1
(see 4.1).
4.6 Ethylene oxide resistometer performance requirements
4.6.1 Measurement accuracy
The EO resistometer shall be capable of measuring the variables listed in Table 3 within the limits there given.
Table 3 — EO resistometer instrumentation requirements (measurement and recording)
Response time
a
Measurement Unit Scale range Resolution
Accuracy (+/−)
ms
Time constant HH:MM:SS Selectable 00:00:01 00:00:01 —
Temperature °C 25 to 80 0,1 0,5 u 500
Vacuum kPa 0 to 100 0,1 1,0 u 30
Pressure kPa 100 to 200 0,1 3,5 u 30
b
Relative humidity % RH 20 to 90 1 5 15 000
5 % of the
Sterilizing agent
mg/l 25 to 1 200 — concentration —
concentration
targeted
a
Accuracy over the test condition range (see 4.1).
b
If relative humidity is not determined by partial pressure.
4.6.2 Recording interval
The measurement system shall have a recording interval for each of the measurements specified in Table 3,
of not less than one data point every 10 s.
The percentage relative humidity and sterilizing agent concentration shall be measured by direct
measurement using a suitable sensor, or determined from pressure measurements during steady state stages
of the operating cycle.
4.6.3 Process control
The EO resistometer process control shall be capable of producing the conditions given in Table 4.
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ISO 18472:2006(E)
Table 4 — EO resistometer physical design/control specifications
Parameter Units Range Tolerance
...