SIST EN ISO 14937:2001

SLOVENSKI STANDARD
SIST EN ISO 14937:2001
01-november-2001
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Sterilization of health care products - General requirements for characterization of a
sterilizing agent and the development, validation and routine control of a sterilization
process for medical devices (ISO 14937:2000)
Sterilisation von Produkten für die Gesundheitsfürsorge - Allgemeine Anforderungen an
die Charakterisierung eines Sterilisiermittels und an die Entwicklung, Validierung und
Routineüberwachung eines Sterilisationsverfahrens für Medizinprodukte (ISO
14937:2000)
Stérilisation des produits de santé - Exigences générales pour la caractérisation d'un
agent stérilisant et pour le développement, la validation et la vérification de routine d'un
processus de stérilisation pour dispositifs médicaux (ISO 14937:2000)
Ta slovenski standard je istoveten z: EN ISO 14937:2000
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 14937:2001 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

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INTERNATIONAL ISO
STANDARD 14937
First edition
2000-12-15
Sterilization of health care products —
General requirements for characterization
of a sterilizing agent and the development,
validation and routine control of a
sterilization process for medical devices
Stérilisation des produits de santé — Exigences générales pour la
caractérisation d'un agent stérilisant et pour le développement, la validation
et la vérification de routine d'un processus de stérilisation pour dispositifs
médicaux
Reference number
ISO 14937:2000(E)
©
ISO 2000

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ISO 14937:2000(E)
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ii © ISO 2000 – All rights reserved

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ISO 14937:2000(E)
Contents Page
Foreword.v
Introduction.vi
1 Scope .1
2 Normative references .1
3 Terms and definitions .2
4 Quality system elements.5
4.1 General.5
4.2 Assignment of responsibilities .5
4.3 Documentation and records.5
4.4 Design control.6
4.5 Calibration .6
5 Sterilizing agent characterization .6
5.1 General.6
5.2 Sterilizing agent .6
5.3 Microbicidal effectiveness .6
5.4 Material effects.7
5.5 Safety and the environment.7
6 Process and equipment characterization .7
6.1 General.7
6.2 Process characterization .8
6.3 Equipment characterization.8
7 Product definition .8
8 Process definition.9
9 Validation.10
9.1 General.10
9.2 Installation qualification.10
9.3 Operational qualification.11
9.4 Performance qualification.11
9.5 Review and approval of validation.12
10 Routine monitoring and control.12
11 Product release from sterilization.12
12 Maintaining process effectiveness .12
12.1 General.12
12.2 Maintenance of equipment .13
12.3 Requalification .13
12.4 Assessment of change.13
Annex A (normative) Factors to be considered in selection of microorganisms for demonstrating
microbicidal effectiveness.14
Annex B (normative) Approach 1 — Process definition based on inactivation of the microbial
population in its natural state.16
Annex C (normative) Approach 2 — Process definition based on inactivation of reference
microorganisms and knowledge of bioburden on product items to be sterilized.17
Annex D (normative) Approach 3 — Conservative process definition based on inactivation of
reference microorganisms.18
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ISO 14937:2000(E)
Annex E (informative) Guidance on application of this International Standard .20
Annex ZA (informative) Corresponding International and European Standards.33
Bibliography .34
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ISO 14937:2000(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 3.
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 International Standard may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights.
International Standard ISO 14937 was prepared by Technical Committee ISO/TC 198, Sterilization of health care
products.
Annexes A, B, C and D form a normative part of this International Standard. Annexes E and ZA are for information
only.
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ISO 14937:2000(E)
Introduction
A sterile medical device is one which is free of viable microorganisms. When it is necessary to supply a sterile medical
device, International Standards specifying requirements for validation and routine control of sterilization processes
require that adventitious microbiological contamination of a medical device prior to sterilization be minimized. Even so,
medical devices produced under standard manufacturing conditions in accordance with the requirements for quality
systems (see, for example, ISO 13485 and ISO 13488) or which have been subjected to a cleaning process as part of
their reprocessing in a health care establishment may, prior to sterilization, have microorganisms on them, albeit in low
numbers. Such products are non-sterile. The purpose of sterilization is to inactivate the microbiological contaminants
and thereby transform the non-sterile products into sterile ones.
The kinetics of inactivation of a pure culture of microorganisms by physical and/or chemical agents used to sterilize
medical devices can generally best be described by an exponential relationship between the numbers of
microorganisms surviving and the extent of treatment with the sterilizing agent. Inevitably this means that there is
always a finite probability that a microorganism may survive regardless of the extent of treatment applied. For a given
treatment, the probability of survival is determined by the number and resistance of microorganisms and by the
environment in which the organisms exist during treatment. It follows that the sterility of any one product in a population
subjected to sterilization processing cannot be guaranteed, and the sterility of a processed population has to be defined
in terms of the probability of there being a viable microorganism present on a product.
This International Standard describes requirements which will enable sterilizer manufacturers, medical device
manufacturers and health care facilities to demonstrate that a process intended to sterilize medical devices has
appropriate microbicidal activity, and that this activity is both reliable and reproducible, such that the relationship for the
inactivation of microorganisms can be extrapolated with reasonable confidence to low levels of probability of there
being a viable microorganism present on a product after sterilization processing. This International Standard does not
specify the maximal value to be taken by this probability; specification of this probability is a matter for regulatory
authorities and may vary from country to country (see, for example, EN 556 and AAMI ST67).
Generic requirements of the quality system for design/development, production, installation and servicing are given in
the ISO 9000 series and particular requirements for quality systems for medical device production in ISO 13485 and
ISO 13488. The standards for quality systems recognize that, for certain processes used in manufacturing or
reprocessing, the effectiveness of the process cannot be fully verified by subsequent inspection and testing of the
product. Sterilization is an example of such a process. For this reason, sterilization processes are validated for use, the
performance of the sterilization process monitored routinely and the equipment maintained.
Exposure to a properly validated, accurately controlled sterilization process is not the only factor associated with the
provision of reliable assurance that the product is sterile and, in this respect, suitable for its intended use. Attention is
given to a number of factors, including:
a) for a manufacturing process, the microbiological status of incoming raw materials and/or components;
b) the validation and routine control of the cleaning and disinfection procedures used during reprocessing;
c) the control of the environment in which the product is manufactured, assembled and packaged, together with
control of personnel and their hygiene; and,
d) the manner in which the items are packaged and the conditions under which the sterilized items are stored.
The type of contamination on a product to be sterilized varies, and this impacts upon the effectiveness of a sterilization
process. Products that have been used in a health care setting, and are being presented for resterilization in
accordance with the manufacturer's instructions, should be regarded as a special case. There is the potential for such
products to possess a wide range of contaminating microorganisms and residual inorganic and/or organic
contamination, in spite of the application of a cleaning process. Hence, particular attention is given to the validation and
control of the cleaning and disinfection processes used during reprocessing.
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ISO 14937:2000(E)
Sterilization technology is at several levels of development and application. There are processes which are developed
and have been in use for appreciable periods, and there are processes which are being developed and introduced
either for sterilization of specific products or for general application. Furthermore, there may be processes which have
yet to be discovered. Experience has identified the requirements which are appropriate for existing sterilization
technologies, and these requirements have been specified in International Standards specific to each established
process. The intention in developing this International Standard is to use this experience to provide, for suppliers of
sterilization technologies, to their users and to regulatory authorities, a knowledge of the relevant general requirements
that will allow development of additional sterilization technologies to continue within a broad framework until sufficient
experience, confidence and demand exist to justify the preparation of a specific International Standard.
This International Standard has three distinct applications:
� for manufacturers of health care products who wish to apply to their products a sterilization process for which a
specific International Standard does not exist; and,
� for manufacturers and users of sterilization systems in health care settings for which a specific International
Standard does not exist; and,
� to provide a framework for the preparation or revision of standards for specific sterilization processes.
The responsibility for carrying out the activities required by this International Standard will vary from case to case. This
International Standard requires that the responsibilities of the various parties be defined (see 4.1.1) but does not
specify to whom the responsibilities are allocated. Annex E provides guidance on allocation of responsibility.
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INTERNATIONAL STANDARD ISO 14937:2000(E)
Sterilization of health care products — General requirements for
characterization of a sterilizing agent and the development,
validation and routine control of a sterilization process for medical
devices
1 Scope
1.1 This International Standard specifies general requirements for the characterization of a sterilizing agent, and
for the development, validation and routine control of a sterilization process for medical devices.
1.2 This International Standard applies to sterilization processes in which microorganisms are inactivated by
physical and/or chemical means.
1.3 This International Standard does not apply to processes that rely solely on physical removal of
microorganisms (for example, filtration).
1.4 This International Standard does not describe detailed test procedures for assessing microbial inactivation.
1.5 This International Standard is intended to be applied by process developers, manufacturers of sterilization
equipment, manufacturers of medical devices to be sterilized and the organization with responsibility for sterilizing
the medical device.
1.6 This International Standard does not supersede or modify published International Standards for particular
sterilization processes.
NOTE 1 Although the scope of this International Standard is limited to medical devices, the principles described may also be
applied to other health care products.
NOTE 2 Sterilization processes validated and controlled in accordance with the requirements of this International Standard
should not be assumed to be effective in inactivating the causative agents of spongiform encephalopathies such as scrapie,
bovine spongiform encephalopathy and Creutzfeld-Jakob disease. Specific recommendations have been produced in particular
countries for the processing of materials potentially contaminated with these agents.
2 Normative references
The following normative documents contain provisions which, through reference in this text, constitute provisions of
this International Standard. For dated references, subsequent amendments to, or revisions of, any of these
publications do not apply. However, parties to agreements based on this International Standard are encouraged to
investigate the possibility of applying the most recent editions of the normative documents indicated below. For
undated references, the latest edition of the normative document referred to applies. Members of ISO and IEC
maintain registers of currently valid International Standards.
ISO 10012-1, Quality assurance requirements for measuring equipment — Part 1: Metrological confirmation system
for measuring equipment.
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing.
ISO 10993-17, Biological evaluation of medical devices — Part 17: Establishment of allowable limits for leachable
substances using health-based risk assessment.
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ISO 14937:2000(E)
ISO 11138-1, Sterilization of health care products — Biological indicators — Part 1: General.
ISO 11140-1, Sterilization of health care products — Chemical indicators — Part 1: General requirements.
ISO 11737-1, Sterilization of medical devices — Microbiological methods — Part 1: Estimation of population of
microorganisms on products.
ISO 11737-2, Sterilization of medical devices — Microbiological methods — Part 2: Tests of sterility performed in
the validation of a sterilization process.
ISO 13485, Quality systems — Medical devices — Particular requirements for the application of ISO 9001.
ISO 13488, Quality systems — Medical devices — Particular requirements for the application of ISO 9002.
IEC 61010-1, Safety requirements for electrical equipment for measurement, control and laboratory use — Part 1:
General requirements.
3 Terms and definitions
For the purposes of this International Standard, the following terms and definitions apply.
3.1
bioburden
population of viable microorganisms on a product and/or a package
3.2
biological indicator
microbiological test system providing a defined resistance to a specified sterilization process
3.3
change control
formal assessment and determination of the appropriateness of a proposed alteration to product or procedure
3.4
chemical indicator
system that reveals a change in one or more predefined process variables based on a chemical or physical change
resulting from exposure to a process
3.5
development
act of elaborating a specification in preparation for validation
3.6
establish
determine by theoretical evaluation and confirm by experimentation
3.7
fault
one or more of the process parameters which lies outside of its/their specified tolerance(s)
3.8
health care product
medical device, medicinal product (pharmaceuticals and biologics) or in vitro diagnostic medical device
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ISO 14937:2000(E)
3.9
installation qualification
IQ
obtaining and documenting evidence that equipment has been provided and installed in accordance with its
specification
3.10
material safety data sheet
document specifying the properties of a material, its potential hazardous effects for humans and the environment,
and the precautions necessary to handle and dispose of the material safely
3.11
medical device
any instrument, apparatus, appliance material or other article, whether used alone or in combination, including the
software necessary for its proper application intended by the manufacturer to be used for human beings for the
purpose of:
� diagnosis, prevention, monitoring, treatment or alleviation of disease;
� diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap;
� investigation, replacement or modification of the anatomy or of a physiological process;
� control of conception;
and which does not achieve its principal intended action in or on the human body by pharmacological,
immunological or metabolic means, but which may be assisted in its function by such means
3.12
operational qualification
OQ
process of obtaining and documenting evidence that installed equipment operates within predetermined limits when
used in accordance with its operational procedures
3.13
parametric release
declaration that a product is sterile, based on the records demonstrating that the process parameters were
delivered within specified tolerances
3.14
performance qualification
PQ
process of obtaining and documenting evidence that the equipment, as installed and operated in accordance with
operational procedures, consistently performs in accordance with predetermined criteria and thereby yields product
meeting its specification
3.15
process challenge device
item designed to simulate product to be sterilized and to constitute a defined challenge to the sterilization process,
and used to assess the effective performance of the process
3.16
process parameter
specified value for a process variable
NOTE The specification for a sterilization process includes the process parameters and their tolerances.
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ISO 14937:2000(E)
3.17
process variable
condition associated with a sterilization process, changes in which alter microbicidal effectiveness
NOTE Process variables may include, for example, time, temperature, pressure, concentration, humidity, wavelength.
3.18
recognized culture collection
international depository authority under the Budapest Treaty on ‘The International Recognition of the Deposit of
Microorganisms for the Purpose of Patent and Regulation’
3.19
reference microorganism
microbial strain obtained from a recognized culture collection
3.20
requalification
repetition of part of validation for the purpose of confirming the continued acceptability of a specified process
3.21
services
supplies from an external source, necessary for the correct functioning of sterilizing equipment
NOTE Examples of services are electricity, water, compressed air, and drainage.
3.22
specify
stipulate in detail within an approved document
3.23
sterile
free from viable microorganisms
3.24
sterility
state of being free from viable microorganisms
3.25
sterilization
validated process used to render a product free from viable microorganisms
3.26
sterilization load
product to be, or that has been, sterilized together using a given sterilization process
3.27
sterilization process
series of actions or operations to achieve the specified requirements for sterility
NOTE This series of actions or operations includes pre-treatment (if necessary), exposure to the sterilizing agent under
defined conditions and any necessary post-treatment. It does not include any cleaning, disinfection or packaging operations that
precede the sterilization process.
3.28
sterilizing agent
physical or chemical entity, or combination of entities, that have sufficient microbicidal activity to achieve sterility
under defined conditions
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ISO 14937:2000(E)
3.29
survivor curve
graphical representation of the inactivation of a population of microorganisms with increasing exposure to a
microbicidal agent under stated conditions
3.30
test for sterility
test defined in an official Pharmacopoeia for product release following exposure to a sterilization process
3.31
test of sterility
test performed as part of development, validation or requalification to establish the presence or absence of viable
microorganisms on product units, or portions thereof
3.32
validation
documented procedure for obtaining, recording and interpreting the results required to establish that a process will
consistently yield product complying with predetermined specifications
4 Quality system elements
4.1 General
The purpose of the quality system is to define and document procedures, the implementation of which control all
stages of development, application and use of the sterilization process. It is not a requirement of this International
Standard to have a complete quality system during design/development and production, but certain elements of a
quality system are required and these are normatively referenced at appropriate places in the text. Attention is
drawn to ISO 9001 and ISO 13485 which describe a quality system. This International Standard does not require
third party assessment of the specified quality system elements.
4.2 Assignment of responsibilities
4.2.1 The responsibility for performing each element of the procedures in this International Standard shall be
defined and documented. Responsibility for each element may vary from case to case and this International
Standard does not allocate responsibility for each element to particular parti
...