ISO 11134:1994
(Main)Sterilization of health care products — Requirements for validation and routine control — Industrial moist heat sterilization
Sterilization of health care products — Requirements for validation and routine control — Industrial moist heat sterilization
Specifies requirements for the use of moist heat in sterilization process development, validation of the sterilization process and control of routine sterilization. Covers all moist heat processes, including saturated steam and air-steam mixtures, and applies to all industrial manufacturers and all others who perform contract moist heat sterilization. Although moist heat sterilization in non-industrial health care facilities is not specifically covered, the principles outlined may be useful to the user of moist heat sterilization in these facilities.
Stérilisation des produits de santé — Prescriptions pour la validation et le contrôle de routine — Stérilisation industrielle à la vapeur d'eau
General Information
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Standards Content (Sample)
INTERNATIONAL IS0
11134
STANDARD
First edition
1994-02-01
Sterilization of health care products -
Requirements for validation and routine
control - Industrial moist heat
sterilization
St&ilisa tion des produits sanitaires - Prescriptions pour la validation et
le contrdle de routine - St&ilisa tion indus trielle par chaleur humide
Reference number
IS0 11134:1994(E)
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IS0 11134:1994(E)
Contents
Page
1
1 Scope . . . . . . . . . . . . . . . . . . .~.*.*.*.~
1
.~.,,.,.,,,.,~.~.~.
2 Normative references
1
. . . . . . . . . . .*.*.
3 Definitions
2
4 General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3
5 Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .*.*.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
6 Sterilization process development
..,....,,.,.,,,..,.,,............................. 5
7 Sterilization process validation
6
. . . . . . . . . . . . . . . . . . . . . . . . . . . .*.
8 Routine moist heat sterilization
Annexes
A Guidance for validation and routine control of industrial moist heat
8
sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
18
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .*.
B Sterilization cycles
22
C Bibliography .,.,,,.,.,.,,,,,.,,,.,.,.,.
0 IS0 1994
All rights reserved. No part of this publication may be reproduced or utilized in any form or
by any means, electronic or mechanical, including photocopying and microfilm, without per-
mission in writing from the publisher.
International Organization for Standardization
Case Postale 56 l CH-1211 Geneve 20 l Switzerland
Printed in Switzerland
ii
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IS0 11134:1994(E)
Foreword
IS0 (the International Organization for Standardization) is a worldwide
federation of national standards bodies (IS0 member bodies). The work
of preparing International Standards is normally carried out through IS0
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. IS0
collaborates closely with the International Electrotechnical Commission
(IEC) on all matters of electrotechnical standardization.
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.
International Standard IS0 11134 was prepared by Technical Committee
lSO/TC 198, Sterilization of health care products.
Annexes A, B and C of this International Standard are for information only.
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IS0 11134:1994(E)
Introduction
The manufacture of a safe and sterile health care product requires atten-
tion to product characteristics and to sterilization methods and controls.
This International Standard provides the essential elements of good
manufacturing practice for moist heat sterilization of health care products.
A sterile product is one that is free of viable microorganisms. Even items
produced under controlled manufacturing conditions may, prior to steril-
ization, have microorganisms on them. Such products are, by definition,
non-sterile. The purpose of sterilization processing is to destroy the
microbiological contaminants on these non-sterile products.
The destruction of microorganisms by physical and chemical agents fol-
lows an exponential law. Accordingly, one can calculate a finite probability
of a surviving microorganism regardless of the magnitude of the delivered
sterilization dose or treatment.
The probability of survival is a function of the number and types (species)
of microorganisms present on the product, the sterilization process
lethality, and, in some instances, the environment in which the organisms
exist during treatment.
It follows that the sterility of individual items in a population of products
sterilized cannot be guaranteed in the absolute sense. The probability of
non-sterility of each individual product unit is derived mathematically. For
example, with a probability of 10w6, the likelihood of a non-sterile product
unit is less than or equal to one in a million.
Requirements for the quality system for the design, development, pro-
duction, supply, installation and servicing of health care products are given
in the IS0 9000 series of Standards.
The IS0 9000 series of Standards designates certain processes used in
the manufacture of health care products as “special” in that the result
cannot be fully verified by subsequent inspection or testing of the product.
Sterilization is an example of a special process because efficacy cannot
be verified by inspection or testing of the product. For this reason, steril-
ization processes must be validated before use, the process routinely
monitored and the equipment maintained.
iv
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INTERNATIONAL STANDARD IS0 11134:1994(E)
Sterilization of health care products - Requirements
- Industrial moist
for validation and routine control
heat sterilization
IS0 9001: 1987, Quality systems - Model for quality
1 Scope
assurance in design/development, production, instal-
la tion and servicing.
This International Standard specifies requirements for
the use of moist heat in sterilization process devel-
IS0 9002:1987, Quality systems - Model for quality
opment, validation of the sterilization process and
assurance in production and ins talla tion.
control of routine sterilization.
IS0 9003: 1987, Quality systems - Model for quality
It covers all moist heat processes, including saturated
assurance in final inspection and test.
steam and air-steam mixtures, and applies to all in-
dustrial manufacturers and all others who perform
IS0 11138-I: -1) Sterilization of health care products
contract moist heat sterilization. Although moist heat
- Biological indi’cators - Part I: General.
sterilization in non-industrial health care facilities is not
specifically covered in this International Standard, the
I EC 101 O-l : 1990, Safety requirements for electrical
principles outlined may be useful to the user of moist
equipment for measurement, control, and labora tory
heat sterilization in these facilities.
use - Part I: General requirements.
NOTE 1
While the general requirements of this Inter-
I EC 101 o-2-041 , Safety requirements for electrical
national Standard may apply to the sterilization of pharma-
ceuticals, other technical or regulatory requirements may equipment for measurement, control, and labora tory
also apply.
use - Part 2-04 1: Particular requirements for
autoclaves using steam for the treatment of medical
This International Standard does not cover the quality materials and for labora tory purposes.
assurance system which is necessary to control all
stages of manufacture, including the sterilization pro-
cess.
3 Definitions
For the purposes of this International Standard, the
following definitions apply.
2 Normative references
The following standards contain provisions which, 3.1 air-steam mixture: Uniform mixture of air and
through reference in this text, constitute provisions saturated steam used for sterilization.
of this International Standard. At the time of publi-
NOTE 2 Air is used to compensate for pressures gener-
cation, the editions indicated were valid. All standards
ated within sealed containers that exceed saturated steam
are subject to revision, and parties to agreements
pressures.
based on this International Standard are encouraged
to investigate the possibility of applying the most re-
cent editions of the standards indicated below. 3.2 bioburden: Population of viable microorganisms
Members of IEC and IS0 maintain registers of cur- on a raw material, component, a finished product
rently valid International Standards. and/or a package.
1) To be published.
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IS0 11134:1994(E)
3.3 certification: Documented review and approval functions within predetermined limits when operated
process carried out as a final step in the validation in accordance with operational instructions.
programme to permit product release.
3.17 recommissioning: Repetition of part or all of
the commissioning test requirements for the purpose
3.4 D value: Exposure time required under a defined
of reconfirming process reliability.
set of conditions to cause a l-logarithm or 90 % re-
duction in the population of a particular microorgan-
3.18 revalidation: Repetition of part or all of the
ism.
validation test requirements for the purpose of re-
confirming process reliability.
35 electromechanical control: Control system that
uses mechanical means (e.g. cams or punch cards) to
3.19 saturated steam: Water vapour at a tempera-
time and initiate the electrical control signals.
ture corresponding to the boiling point of the source
liquid.
36 . environmental controls: Controls established
in the product manufacturing areas to control biobur-
3.20 simulated product load: Load that is used as
den.
an alternative to the actual product load and that rep-
resents an equal or greater challenge to the process.
NOTE 3 These may include air and fluid filters, surface
disinfection, personnel uniforms and administrative pro-
3.21 sterile: State of being free from viable micro-
cedures.
organisms.
.
37 F ’ value: Measure of the micro lb1 ological inacti-
NOTE 6 In practice no such absolute statement regarding
v&i0 in capability of a heat sterilization recess.
P
the absence of microorganisms can be proven (see steril-
ization).
3.8 FO value: F value calculated at 121,l “C
(250 “F) with a z value of 10 K and a D value of
3.22 sterilization: Validated process used to render
1 min.
a product free of all forms of viable microorganisms.
3.9 materials of construction: Materials used in
NOTE 7 In a sterilization process, the nature of micro-
the sterilization equipment composition.
biological death is described by an exponential function.
Therefore, the presence of microorganisms on any individ-
ual item may be expressed in terms of probability. While
3.10 microbiological challenge: Biological indi-
this probability may be reduced to a very low number, it can
cators, biological-indicator test packs, or inoculated
never be reduced to zero.
product that contain known populations of micro-
organisms and can be used in testing sterilization cy-
3.23 sterilization cycle: Automatic sequence of op-
cles.
erating stages performed in the sterilizer.
3.11
moist heat: Heat that is derived from water,
3.24 sterilization process development: Studies
either as a liq uid or as steam under pressure.
conducted to develop a reproducible process by
which the product may be sterilized to the desired
3.12 moist heat sterilization: Process of using
probability of a non-sterile unit without damage.
moist heat to produce a sterile product.
3.25 validation: Documented procedure for obtain-
3.13 primary packaging: Element of the packaging
ing, recording and interpreting the results required to
system that maintains the sterility of the product.
establish that a process will consistently yield product
complying with predetermined specifications.
3.14 process lethality: Capability of the sterilization
process to destroy microorganisms.
NOTE 8 Validation covers three activities: commission-
ing, verification of process specification and performance
NOTE 4 This may be determined by measurements of qualification.
microbial death or by establishing and measuring the re-
quired physical parameters.
3.26 z value: Number of degrees of temperature
required for a l-logarithm change in the D value.
3.15 product carrier system: Mechanism used to
hold the product and its packaging for sterilization.
4 General
NOTE 5 The carrier system should prevent product dam-
age and allow uniform access by the sterilizing agent. 4.1 Responsibilities and training of
personnel
3.16 commissioning: Obtaining and documenting
evidence that equipment has been provided and in- Responsibility for the installation and maintenance of
stalled in accordance with its specification and that it moist heat sterilizers, for the validation and routine
2
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IS0 11134:1994(E)
control of moist heat sterilization, and for the release 5.1.2 Safety
of sterilized product shall be assigned to qualified
all be provided to demon-
personnel as specified in IS0 9001 or IS0 9002. Documen taty evidence sh
strate tha t the sterilization system compli es with the
safety requirements specified in IEC 1010-l and
4.2 Product considerations
IEC 1010-2 and any other standards or regulatory re-
quirements applicable in the country of use.
The product shall be designed to comply with its
specification and requirements for safety and efficacy
following exposure to the maximum number of steril-
5.1.3 Manuals and instructions
ization cycles specified for the product. If any treat-
ment is required prior to sterilization (for example,
As a minimum, the following information shall be
cleaning) this shall also be validated as part of the re-
available for each identified sterilizer in the language
sterilization procedure. The product shall be designed
agreed to by the user:
and materials shall be selected to be compatible with
environmental changes occurring in the sterilization
a) instructions for the installation of the sterilization
chamber during the sterilization cycle.
system sufficient to ensure safe and effective op-
eration of the equipment;
43 . Packaging considerations
b) a list of materials of construction exposed to the
sterilant or to inadvertent contact with the product;
4.3.1 General
c) instructions for safe and effective operation, in-
The packaging shall consist of at least a primary
cluding recommendations for vessel temperature
package and a secondary package.
and pressure limits as well as safety precautions;
The primary package and, if present at the time of
SC hedu les for rou-
d) instr ,uctions and recommended
sterilization, the secondary package shall comply with
tine preventive maintenance;
its specification following sterilization.
e) a repair manual including a list of recommended
4.3.2 Packaging permeability
replacement parts;
The packaging shall permit the attainment of steriliz-
f) chamber drawings sufficient to define configur-
ing, conditions on or within the product either by the
ation and hardware, pipe-work and control system
removal of air and penetration of steam or, for non-
schematic drawings, recommended installation
permeable packaging (e.g. for vials containing liquids),
drawings, and a parts list defining all significant
by heat transfer.
system components;
g) process-control logic and/or software documen-
5 Equipment
tation necessary to operate and maintain the
equipment control system (see 5.2.6). Any soft-
5.1 Documentation
ware supplied shall be accompanied by proof of
validation of its release and revision level.
5.1 .I Identification
5.1.4 Additional information
Each sterilization system shall have one or more in-
formation plates, permanently fastened and marked,
The specifications for a sterilizer to be used for moist
that provide the following information in the language
heat sterilization, including its installation and instal-
agreed to by the user:
lation tests, shall be documented.
name and address of the manufacturer;
a)
b) serial number or other system identification; 5.2 Sterilizer performance, utilities,
components, accessories and controls
c) chamber design pressure and maximum working
temperature;
5.2.1 Performance
d) jacket pressure rating (if applicable);
Sterilization systems used to process health care
e) stamp of inspe ction authority and identif i- products by moist heat shall be provided in accord-
cation ma rk; ance with regulations or standards for sterilization
equipment performance applying in the country of
f) date of primary construction of the vessel. use.
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IS0 11134:1994(E)
5.2.2 Utilities 5.2.6 Control programmes
Programmes used to execute and control the steril-
5.2.2.1 Steam purity and quality shall be specified
ization process, whether microprocessor or electro-
and demonstrated to be adequate for its intended
mechanically based, shall be validated. The
documented control programme shall be evaluated by
procedures designed to demonstrate the correctness
5.2.2.2 The purity of the compressed air used in the
of the programme logic in both process simulated
sterilization chamber shall be such that the safety of
conditions and actual sterilizer use. Any subsequent
the product is not impaired.
changes shall be similarly documented, be evaluated
to assess whether revalidation is required and be ap-
proved by the user.
5.2.2.3 Ambient air admitted to the chamber to re-
lieve the vacuum shall pass through a
microbiological-retentive filter for all products with
5.3 Performance of instruments
packaging that is permeable by air.
5.3.1 Instrument accuracy
5.2.2.4 Water used in the sterilizer as a means of
direct cooling of product shall be specified and verified
5.3.1.1 Accuracy of instruments used for validation
to meet the requirements established during product
shall exceed the accuracy of the controller and re-
development. This shall be documented.
corder system.
5.2.2.5 Electrical power supplied to the sterilization
5.3.1.2 Temperature and pressure sensors shall be
system shall comply with the manufacturer’s specifi-
selected, installed and used in a manner which will
cation.
ensure that the stated accuracy is maintained.
5.2.3 Components 5.3.2 Calibration standards
The materials and components used in the con- The accuracy of standards used to calibrate process
struction of the sterilization system shall be selected measurement instruments shall be specified and cali-
to minimize the potential for microbiological or bration shall be traceable to a national reference
chemical contamination. standard as specified in IS0 9003.
5.3.3 Sterilizer reference instruments
5.2.4 Accessories
The sterilizer shall be equipped with a separate
The system designed to support the product in the
measuring system to verify that values measured by
chamber shall be designed to allow uniform steam
controlling instruments are within the specified tem-
penetration and/or heat transfer. The carrier system
perature and pressure limits during each cycle.
shall also allow drainage of condensate and/or cooling
water, prevent damage to the product and retain the
integrity of the load.
5.3.4 Calibration programme
An effective procedure shall be established, docu-
5.2.5 Control and recording systems
mented and maintained for the calibration of all
controlling, indicating and recording instruments used
The following process paramete rs shall be au toma ti-
for validation and routine control of the sterilization
tally controlled and recorded:
cycle. The procedure shall comply with the require-
ments of IS0 9001, IS0 9002 and, for instruments
a) temperature;
used for validation, IS0 9003.
b) time;
5.4 Maintenance
c) pressure;
5.4.1 A sterilizer shall be maintained in accordance
d) rate of change of temperature and pressure, if re-
with a documented planned preventive maintenance
quired for product integrity.
scheme.
The recorder and process control systems shall either
be independent or designed in a manner that will
5.4.2 Person(s) carrying out maintenance shall have
cause a warning to occur should the difference be- documentary evidence to demonstrate successful
tween a controlled and recorded variable exceed
training in the skills needed to maintain the specified
specified limits. sterilizer(s).
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IS0 11134:1994(E)
5.4.3 The procedure for each planned maintenance
7 Sterilization process validation
task and the frequency with which it is carried out
shall be specified and documented.
7.1 The validation programme shall be performed
using an approved protocol that conforms to the prin-
5.4.4 A sterilizer shall not be used to process health
ciples outlined in IS0 9002.
care products until scheduled and unscheduled main-
tenance tasks have been satisfactorily completed and
recorded accordingly.
7.2 Each production sterilizer shall be commissioned
upon installation. New products and new sterilization
equipment or process conditions shall be validated.
5.4.5 Records of maintenance shall be retained in
an equipment file.
7.3 Validation activities shall be assigned to a des-
5.4.6 The maintenance scheme, maintenance pro-
ignated person experienced in this task.
cedures and maintenance records shall be reviewed
periodically by a designated person.
7.4 The process validation shall consist of a com-
missioning of the systems, a performance quali-
6 Sterilization process development
fication, and certification.
6.1 Except where compliance with the product
7.4.1 The commissioning shall include:
specification would be compromised, sterilization by
saturated steam shall be used. Where other methods
demonstration of compliance with design per-
a)
are to be used (e.g. air-steam mixtures) reproducibility
formance specifications;
of the environment within the chamber shall be dem-
onstrated.
documentation of the equipment (see 5.1.3);
b)
Air-steam mixtures shall only be used in combination
d demonstration of conformance of the quality and
with effective circulation that creates a uniform heat-
capacity of utilities;
ing medium throughout the sterilizer. Where air-steam
mixtures are used and steam penetration is required,
calibration of both operating and test instrumen-
d)
the circulation system shall create a uniform air-steam
tation; and
mixture within the load.
when applicable, demonstration of efficacy of air
e)
6.2 The sterilization cycle shall be developed to be
removal.
reproducible during routine processing.
7.4.2 The performance qualification shall include:
6.3 The attainment of sterilizing conditions in the
product processed in newly-developed moist heat
demonstration of process reproducibility (through
a)
sterilization cycles shall be demonstrated.
the use of sufficient cycles);
6.4 Any product handling or storage after steril- demonstration of uniformity within specified limits
b)
ization at the site of sterilization shall not compromise throughout the chamber and load (through the use
the qualities of the product. of sufficient cycles and sensors);
d demonstration of the relationship between control
6.5 The probability of a non-sterile product unit shall
and load parameters;
be selected to ensure that the sterile health care
product has a sufficiently low probability of a surviving
demonstration of the correlation of physical par-
d)
microorganism to be safe for its intended use.
ameters to microbiological lethality by data taken
from established literature or from original re-
6.6 If indicator microorganisms are used, they shall
search;
be selected with reference to the sterilization process
and shall meet the requirements of IS0 11138-I.
e) demonstration that both maximum and minimum
loading (or specified product mix) are compatible;
6.7 Data generated during cycle development shall
demonstrate that the required probability of survival
if simulated product loads are used, demonstration
f )
of the bioburden has been achieved.
that the simulated product loads are represen-
tative of actual products;
6.8 For sterilization processes based upon biobur-
den, there shall be a bioburden programme which demonstration that qualification loads that will be
9)
determines the numbers and resistance of the bio- re-used have returned to specified conditions be-
burden prior to sterilization. fore re-use; and
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IS0 11134:1994(E)
h) demonstration that the product and packaging d) operator identification and signature;
comply with the specification after sterilization
and, where applicable, resterilization. e) cycle start time (real time);
f) chamber pressure throughout the cycle;
7.4.3 The number of temperature sensors to be
used for performance qualification and performance
g) chamber temperature throughout the cycle;
requalification shall be specified. Documented evi-
dence shall be provided to demonstrate that this
h) timing of critical process parameters.
number is sufficient to establish that the process
conforms to specifications generated during process
development.
8.2 Change control
7.4.4 The calibration of temperature measurement
There shall be documented procedures in place to
systems used for validation shall be verified before
ensure that no changes take place in equipment, pro-
and after each programme of sequential tests. cess or materials that could affect the sterilization
process. If such changes do occur as a planned event,
the new sterilization cycle shall be validated. Process
7.5 At the completion of the validation there shall
failures that cannot be attributed to lack of adherence
be a formal review and approval of the recorded data.
to process specifications shall be examined to deter-
mine the need for requalification.
7.6 Revalidation shall be done whenever there has
been a major repair to the sterilization system that
8.3 Periodic testing
could affect the efficacy of the process. Revalidation
shall also be performed at least once every
Steri lizers shall be tested periodically in accordance
12 months.
with a documen ted plan.
7.7 Procedures for revalidation, review and im-
8.4 Microbiological testing
plementation of changes to the process, sterilization
system (hardware and software), product or packag-
If the efficacy of the process cycle is based on a study
ing shall be documented. The procedures shall include
or estimate of the bioburden on the product,
the assignment of responsibility for determining the
necessity and extent of repeating elements of the
the method used to determine the bioburden or
original validation studies. a)
the estimate of the bioburden shall be validated
Modifications to equipment or control systems shall
and documented;
be evaluated to confirm that the process conditions
delivered to the product load are comparable to those
means shall be provided to ensure that the limits
b)
originally qualified.
specified for bioburden are not exceeded; and
a continuing programme of product bioburden
d
8 Routine moist heat sterilization
monitoring shall be carried out at a prescribed fre-
quency and the rationale documented.
8.1 Steam sterilization process control
8.5 Release of sterilized products
8.1.1 The accuracy and reliability of instrumentation
To release the product, the process parameters
used to monitor each production cycle shall be
monitored during routine sterilization shall be within
periodically checked for compliance with their specifi-
the validated limits. A system to differentiate between
cation.
processed and unprocessed items shall be used. Only
authorized persons shall release products after steril-
8.1.2 Documented procedures for the routine moni-
ization.
toring of the sterilization cycle shall be provided.
8.6 Audit of operations
8.1.3 For each cycle, a record shall be retained of
the following:
Production and quality control procedures and records
shall be reviewed in accordance with IS0 9001 at
a) date;
least annually. Competent personnel not directly in-
volved in these procedures shall ensure that the pro-
b) sterilizer identification;
cess specifications established during qualification
testing are followed and remain valid.
c) cycle identification;
6
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IS0 11134:1994(E)
reviewed by a designated person to determine the
8.7 Corrective action
proper steps and corrective action required.
Procedures and documentation for corrective action
shall comply with IS0 9001. Any deviations from
8.8 Records
specifications or procedures uncovered during oper-
ations, audits, calibrations or maintenance shall be
Records to demonstrate that the product has been
sterilized in accordance with all specifications shall be
produced and maintained as specified in IS0 9001.
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IS0 11134:1994(E)
Annex A
(informative)
Guidance for validation and routine control of industrial moist heat
sterilization
NOTE 9 The clauses in this annex provide guidance on A.4.2.2 Selection of materials
the related clause in the body of the Standard.
In selecting materials, the ability to withstand the
physical stresses inherent in moist heat sterilization is
A.1 Scope
essential. For some materials, it is also essential
...
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