SIST EN ISO 14160:2000
(Main)Sterilization of single-use medical devices incorporating materials of animal origin - Validation and routine control of sterilization by liquid chemical sterilants (ISO 14160:1998)
Sterilization of single-use medical devices incorporating materials of animal origin - Validation and routine control of sterilization by liquid chemical sterilants (ISO 14160:1998)
Sterilisation von Medizinprodukten für den einmaligen Gebrauch mit Bestandteilen tierischer Herkunft - Validierung und Routineüberwachung der Sterilisation mit flüssigen chemischen Sterilisiermitteln (ISO 14160:1998)
Diese Internationale Norm legt Anforderungen an die Entwicklung, die Validierung sowie die Verfahrensregelung und -überwachung der chemischen Flüssigkeits-Sterilisation von Medizinprodukten für den einmaligen Gebrauch, die ganz oder teilweise aus Materialien tierischen Ursprungs bestehen, fest. Diese Internationale Norm gilt nicht für Materialien menschlicher Herkunft. Diese Internationale Norm beschreibt kein Qualitätssicherungssystem zur Überwachung aller Stufen des Herstellungsverfahrens.
Stérilisation des dispositifs médicaux non réutilisables contenant des matieres d'origine animale - Validation et contrôle de routine de la stérilisation par agents stérilisants chimiques liquides (ISO 14160:1998)
Sterilizacija medicinskih pripomočkov za enkratno uporabo, ki vsebujejo materiale živalskega izvora - Validacija in redni nadzor sterilizacije s tekočimi kemijskimi sredstvi za sterilizacijo (ISO 14160:1998)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
SIST EN ISO 14160:2000
01-januar-2000
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åLYDOVNHJDL]YRUD9DOLGDFLMDLQUHGQLQDG]RUVWHULOL]DFLMHVWHNRþLPLNHPLMVNLPL
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Sterilization of single-use medical devices incorporating materials of animal origin -
Validation and routine control of sterilization by liquid chemical sterilants (ISO
14160:1998)
Sterilisation von Medizinprodukten für den einmaligen Gebrauch mit Bestandteilen
tierischer Herkunft - Validierung und Routineüberwachung der Sterilisation mit flüssigen
chemischen Sterilisiermitteln (ISO 14160:1998)
Stérilisation des dispositifs médicaux non réutilisables contenant des matieres d'origine
animale - Validation et contrôle de routine de la stérilisation par agents stérilisants
chimiques liquides (ISO 14160:1998)
Ta slovenski standard je istoveten z: EN ISO 14160:1998
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
SIST EN ISO 14160:2000 en
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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INTERNATIONAL ISO
STANDARD 14160
First edition
1998-03-15
Sterilization of single-use medical devices
incorporating materials of animal origin —
Validation and routine control of
sterilization by liquid sterilants
Stérilisation des dispositifs médicaux non réutilisables contenant des
matières d’origine animale — Validation et contrôle de routine de la
stérilisation par agents stérilisants chimiques liquides
A
Reference number
ISO 14160:1998(E)
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ISO 14160:1998(E)
Contents Page
1 Scope . 1
1
2 Normative references .
2
3 Definitions .
4 General. 4
5 Validation . 5
6 Process control and monitoring . 7
7 Product release from sterilization . 9
Annexes
A Guidance . 10
B References to European Standards with their relevant equi-
valents . 19
C Bibliography . 21
© ISO 1998
All rights reserved. Unless otherwise specified, 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 permission in writing from the publisher.
International Organization for Standardization
Case postale 56 • CH-1211 Genève 20 • Switzerland
Internet central@iso.ch
X.400 c=ch; a=400net; p=iso; o=isocs; s=central
Printed in Switzerland
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ISO 14160:1998(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.
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 ISO 14160 was prepared by Technical Committee
ISO/TC 198, Sterilization of health care products.
Annexes A, B and C of this International Standard are for information only.
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Introduction
A sterile product item is one which is free of viable microorganisms.
International Standards require, when it is necessary to supply a sterile
product item, that adventitious microbiological contamination of a medical
device from all sources prior to sterilization be minimized by all practical
means. Even so, product items produced under defined manufacturing
conditions in accordance with the requirements for quality systems for
medical devices (see ISO 13485 and ISO 13488) can, prior to sterilization,
have microorganisms on them, albeit in low numbers. Such product items are
non-sterile. The purpose of sterilization processing is to inactivate the
microbiological contaminants and thereby transform the non-sterile items into
sterile ones.
The inactivation of a pure culture of microorganisms by physical and/or
chemical agents used to sterilize medical devices often approximates an
exponential relationship; inevitably this means that there is always a finite
probability that a microorganism can survive regardless of the extent of
treatment applied. For a given treatment, the probability of survival is
determined by the number and types of microorganisms and by the
environment in which the organisms exist during treatment. It follows that the
sterility of any one item in a population of items subjected to sterilization
processing cannot be guaranteed and the sterility of the processed
population of items has to be defined in terms of the probability of there being
a viable microorganism present on the device.
Generic requirements for the quality system for the design/development,
production, installation and servicing are given in the ISO 9000 family of
standards and in ISO 13485 and ISO 13488. The ISO 9000 series of
standards designates certain processes used in manufacture as "special" if
the results cannot be fully verified by subsequent inspection and testing of
the product. Sterilization is an example of a special process because process
efficacy cannot be verified by inspection and testing of the product. For this
reason, sterilization processes have to be validated before use, the
performance of the process monitored routinely and the equipment
maintained.
It is important to be aware that the exposure to a properly validated and
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 has also to be given to a
number of factors, including the microbiological status (bioburden) of
incoming raw materials and/or components, their subsequent storage, and to
the control of the environment in which the product is manufactured,
assembled and packaged.
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The agents for sterilization used most frequently for medical devices are
moist heat, dry heat, irradiation and ethylene oxide. While some devices
containing animal tissues may be compatible with these commonly applied
methods of sterilization (for example catgut sutures are usually sterilized by
irradiation), other devices, such as biological heart valves or tissue patches,
are not compatible with conventional sterilization processes. It has been
recognized that other sterilizing agents might have to be used in these
exceptional circumstances. Liquid chemical sterilants have been widely used
in such instances and, in common with the other sterilization methods, the
efficacy of the process needs to be demonstrated and recorded before it is
adopted for routine use.
This International Standard contains requirements for the validation and
routine monitoring of sterilization of single-use medical devices containing
materials of animal origin by exposure to liquid chemical sterilants; guidance
on the application of this International Standard is given in annex A.
Manufacturing processes for medical devices containing animal tissues
frequently include exposure to chemical agents which can in themselves
reduce significantly the bioburden on the medical device. Following the
manufacturing process, a medical device is exposed to a defined sterilization
process; the requirements for validation and routine control described in this
International Standard apply only to this defined sterilization process and do
not take account of the lethal effects of other bioburden reduction steps.
NOTE — The guidance given in annex A is not obligatory and it is not provided as a
check list for auditors.
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INTERNATIONAL STANDARD ISO ISO 14160:1998(E)
Sterilization of single-use medical devices incorporating materials
of animal origin — Validation and routine control of sterilization by
liquid chemical sterilants
1 Scope
This International Standard specifies requirements for the development, validation, process control and monitoring of
the sterilization, by the use of liquid chemical sterilants, of single-use medical devices comprising, in whole or in part,
materials of animal origin.
This International Standard does not apply to material of human origin.
This International Standard does not describe a quality assurance system for the control of all stages of manufacture.
NOTE 1 Attention is drawn to the standards for quality systems (see ISO 9001 and ISO 13485 or ISO 9002 and ISO 13488) which
can be used in the control of all stages of manufacture including the sterilization process.
This International Standard does not describe tests to establish the effects of any chosen sterilization method upon the
fitness for use of the medical device.
NOTE 2 Such testing is a crucial part of the design and development of a medical device.
This International Standard does not describe methods for the validation of the inactivation of viruses.
NOTE 3 In developing a method for processing medical devices containing materials of animal origin, consideration of the effects
of liquid chemical sterilization on potential viral contaminants will also be necessary because of the source of materials used in the
manufacture of these particular medical devices. The importance of validation of viral inactivation for processes within the scope of
this International Standard is recognized. This aspect is excluded from this International Standard; a separate European Standard
is in preparation (EN 12442-3).
NOTE 4 Liquid chemical sterilants traditionally employed to sterilize animal tissues in medical devices may not be effective in
inactivating the causative agents of transmissable spongiform encephalopathies such as bovine spongiform encephalopathy
(BSE), or scrapie. Satisfactory validation in accordance with this International Standard should not be assumed to demonstrate
inactivation of infective agents of this type.
This International Standard does not cover the level of residual sterilant within medical devices.
NOTE 5 ISO 14538 is concerned with this issue.
2 Normative references
The following standards contain provisions which, through reference in this text, constitute provisions of this
International Standard. At the time of publication, the editions indicated were valid. All standards are subject to revision,
agreements based on this International Standard are encouraged to investigate the possibility of applying the most
recent editions of the standards indicated below. Members of IEC and ISO maintain registers of currently valid
International Standards.
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ISO 9001:1994, Quality systems — Model for quality assurance in design, development, production, installation and
servicing.
ISO 9002:1994, Quality systems — Model for quality assurance in production, installation and servicing.
ISO 11138-1:1994, Sterilization of health care products— Biological indicators — Part 1: General.
ISO 11737-1:1995, Sterilization of health care products — Microbiological methods — Part 1: Estimation of the
population of microorganisms on product.
NOTE — The relationship between International Standards and European Standards is given in annex B.
3 Definitions
For the purposes of this International Standard, the following definitions apply.
3.1
batch
defined quantity of bulk, intermediate, or finished product that is intended or purported to be uniform in character
and quality, and which has been produced during a defined cycle of manufacture
3.2
bioburden
population of viable microorganisms on a product and/or a package
3.3
carrier
supporting material on which test organisms are deposited
3.4
commissioning
obtaining and documenting evidence that equipment has been provided and installed in accordance with its
specifications and that it functions within predetermined limits when operated in accordance with operational
instructions
3.5
decimal reduction value
D-value
time (expressed in minutes) or irradiation dose (expressed in kilograys) required to achieve inactivation of 90 % of a
population of the test organism under stated exposure conditions
3.6
exposure time
time for which the medical device is exposed at the specified temperature and sterilant concentration
3.7
inactivation
process resulting in the loss of the ability of microorganisms to grow and/or multiply
NOTE — For the purpose of this International Standard, microorganisms comprise sporing and non-sporing bacteria, viruses, fungi
and protozoa.
3.8
inoculated carrier
carrier on which a defined number of test organisms has been deposited
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3.9
liquid chemical sterilant
defined formulation of chemicals in a solution or liquid form which is applied to achieve sterility
3.10
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
3.11
performance qualification
obtaining and documenting evidence that the equipment as commissioned will produce acceptable product when
operated in accordance with the process specification
3.12
presterilization count
viable count obtained prior to sterilization
3.13
product compatibility
ability of the sterilization process to achieve the intended results without detrimental effect on the product
3.14
process development
documented programme of studies which are performed in order to define the sterilization process based upon the
product/packaging/loading pattern and/or equipment limitations
3.15
revalidation
repetition of part or all of the validation test requirements for the purpose of reconfirming process reliability
3.16
sterility
state of being free from viable microorganisms
NOTE — In practice no such absolute statement regarding the absence of microorganisms can be proven (see 3.18 sterilization).
3.17
sterile
free from viable microorganisms
NOTE — In practice no such absolute statement regarding the absence of microorganisms can be proven (see 3.18 sterilization).
3.18
sterilization
validated process used to render a product free of all forms of viable microorganisms
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NOTE — In a sterilization process, the nature of microbial death is described by an exponential function. Therefore, the presence
of viable microorganisms on any individual item can be expressed in terms of probability. While this probability may be reduced to a
very low number, it can never be reduced to zero. The probability can be expressed as a sterility assurance level (SAL), normally
-n
expressed in the form 10
3.19
storage solution
liquid in which a medical device in its final form is presented for use
3.20
validation
documented procedure for obtaining, recording and interpreting the data required to show that a process will
consistently yield product complying with predetermined specifications
NOTE — For sterilization by liquid chemical sterilants, validation is considered as a total programme which consists of
commissioning and performance qualification.
3.21
viable count
number of microorganisms estimated by growth of discrete colonies under the stated culture condition
NOTE — A discrete colony may not necessarily originate from a single viable microorganism.
4 General
4.1 Control of manufacturing
The manufacturing process shall be established and controlled to maintain the presterilization count below a
specified limit.
NOTE 1 Employing a quality system complying with ISO 13485 or ISO 13488 meets this requirement.
A documented system shall be established and maintained to control the sourcing of raw materials of animal origin.
NOTE 2 A European Standard on sourcing, controls, collection and handling (EN 12442-2) is under preparation.
The documented procedures and instructions required by this International Standard shall be implemented
effectively. Documentation and records shall be reviewed and approved by designated personnel (see 4.2).
4.2 Personnel
Responsibility for the maintenance of equipment (see 4.4), for the validation (see clause 5) and routine control (see
clause 6) of sterilization by exposure to liquid chemical sterilants and for the release of product shall be assigned to
qualified personnel as specified in ISO 9001 or in ISO 9002.
4.3 Calibration
An effective system shall be established, documented and maintained for the calibration of all controlling, indicating and
recording instruments used for validation and routine control of the sterilization process. This system shall comply with
the requirements of either ISO 9001 or ISO 9002.
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4.4 Maintenance of equipment
Preventative maintenance shall be planned and performed in accordance with documented procedures. The
procedure for each planned maintenance task and the frequency at which it is to be carried out shall be specified
and documented.
Equipment shall not be used to process medical devices unless all maintenance tasks have been satisfactorily
completed and recorded.
Records of maintenance shall be retained as specified in ISO 9001 or ISO 9002.
The maintenance scheme, maintenance procedures and maintenance records shall be reviewed periodically by a
designated person (see 4.2).
4.5 Process development and product compatibility
4.5.1 Prior to the introduction of a new or altered product, package, loading pattern or sterilization process, the
sterilization process to be validated shall be defined and documented.
A demonstration of equivalence to previously validated product, package or loading pattern shall be considered to meet
this requirement. Any demonstration of equivalence shall be documented.
NOTE — The specified sterilization process may comprise separate treatments with more than one liquid chemical sterilant.
4.5.2 Product and packaging shall be designed to allow contact with liquid chemical sterilant and so that residues
of the liquid chemical sterilant are below levels as specified by the manufacturer. The location within the product at
which sterilization is most difficult to achieve shall be identified.
4.5.3 It shall have been demonstrated and documented that the sterilization process does not affect adversely the
fitness for use of the product or its packaging. If resterilization is to be permitted, the effects of such processing shall
be evaluated and documented.
5 Validation
5.1 General
Procedures for validation shall be documented and records of each validation shall be retained (see 5.4.1).
5.2 Commissioning
Commissioning shall demonstrate that the specifications for equipment used for the sterilization process are met.
5.3 Performance qualification
5.3.1 The performance qualification shall demonstrate that the sterilization process has:
a) appropriate lethal activity against a representative range of microorganisms (see 5.3.5, 5.3.6 and A.5);
b) defined processing parameters (e.g., time, temperature, liquid chemical sterilant concentration, pH) which are
capable of control throughout the process.
5.3.2 For the performance qualification, the part of the product which is most difficult to sterilize, as defined according
to 4.5.2, shall be taken into consideration during the performance qualification.
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5.3.3 The presterilization count of the product shall be established as described in ISO 11737-1.
5.3.4 Before performance qualification is undertaken, a method shall be validated for the neutralization of the liquid
chemical sterilant prior to culturing survivors. The method shall not in itself adversely influence the ability to interpret the
results.
5.3.5 The combination of conditions with the lowest microbicidal activity within the process specification shall be
identified and this combination of conditions shall be used in the performance qualification.
5.3.6 Microbiological performance qualification shall include the following three stages:
a) A screening test to identify microorganisms with a high resistance to the process (see A.4.2.3).
b) Determination of inactivation kinetics.
This consists of the construction of log survival curves for the microorganisms identified as having a high
resistance to the process. The inactivation curve shall include a minimum of 5 points covering at least a thousand-
fold reduction in numbers (see also A.4.2.4.1 and A.4.2.5). If the product does not allow the above-mentioned
procedure, the MPN method as specified in A.4.2.4.2 may be used. This shall be rationalized and documented.
Microorganisms shall be presented to the process on carrier material(s) representative of the medical device.
c) Assessment of inactivation of the microorganisms from the presterilization count as they are induced to grow onto
carriers of tissue.
The range of microorganisms employed, in addition to isolates from the bioburden, shall include microorganisms with a
known high resistance to the sterilization process and, in any event, resistance equivalent to spores of Bacillus subtilis
(see table A.2) complying with ISO 11138-1.
NOTE — In the design of such experiments, consideration should be given to the level of organic and/or inorganic contamination
and variation between replicate experiments.
5.3.7 Within the sterilization process, the exposure time shall not be less than D[6 + log (100 + B)] where D is the D-
10
value of the most resistant microorganism identified during performance qualification and B is the value of the
bioburden estimated as described in ISO 11737-1.
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NOTE — The extended treatment specified by this clause provides a probability of at least 1 3 10 of microorganisms surviving
treatment. EN 556 specifies this is a requirement for terminally sterilized devices labelled sterile (see annex C).
5.3.8 If the medical device is subjected to an aseptic transfer following the completion of sterilization process:
a) processes used for the sterilization of components for manufacture (e.g. containers, storage solutions) shall be
validated and routinely controlled in accordance with the appropriate International Standard;
b) transfer procedures after exposure to the liquid chemical sterilant shall be validated in accordance with
ISO 13408 (see A.4.2.7).
5.4 Certification of validation
5.4.1 A validation report containing the results of all validation exercises shall be documented. The report shall be
signed by persons designated as responsible for preparing, reviewing and accepting this report. The validation
report shall be retained as specified in ISO 9001 or in ISO 9002.
5.4.2 The validation report shall contain or reference the documented process specification for liquid chemical
sterilization. The process specification shall specify the medical device for which the validation has been performed
and shall detail, including values and tolerances where appropriate, the following:
a) frequency and method(s) for bioburden estimations, together with action limits;
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b) specification for the environment in which the liquid chemical sterilant and containers are prepared, and aseptic
transfers (see 5.3.8) are undertaken;
c) training and certification criteria for approval of personnel to be authorized to undertake aseptic transfers (see
5.3.8);
d) method of ensuring the absence of viable microorganisms from the liquid chemical sterilant solution(s) (see
A.6);
e) formulation of the liquid chemical sterilant, including the specification of its constituents;
f) pH of the liquid chemical sterilant;
g) residual activity required for the liquid chemical sterilant after the sterilization process in terms of chemical
concentration and/or microbicidal activity;
h) specification of the exposure vessel in which products come into contact with the liquid chemical sterilant,
including materials of construction, size, and details of any pretreatment to be applied;
i) number of products to be sterilized per unit volume of liquid chemical sterilant;
j) exposure time;
k) temperature to be used for sterilization;
l) any other critical process variable(s) determined during process development;
m) method of sterilizing any storage solution in which the product is presented after sterilization (see 5.3.8).
5.4.3 In cases where a validation for a specific device is also judged valid for other devices, the justification for this
shall be documented.
5.5 Revalidation
5.5.1 The validation and any subsequent revalidation data shall be reviewed at least annually and a rationale shall
be prepared and documented whether or not revalidation is required.
A revalidation exercise shall be undertaken unless sufficient data have been generated to demonstrate the continued
appropriateness of the sterilization process. Procedures for the review of validation and revalidation data shall be
documented and records of revalidation shall be retained.
5.5.2 A revalidation report shall be documented. The report shall be signed by the persons designated by the
same functions/organizations that prepared, reviewed and accepted the original validation report (see 5.4.1).
6 Process control and monitoring
6.1 At stipulated intervals, the bioburden shall be estimated as described in ISO 11737-1. If a microorganism that
has not been studied in the original performance qualification is isolated during routine estimation of the
presterilization count, the exercise in 5.3.5 shall be performed with this microorganism.
6.2 Data shall be recorded and retained for each batch of sterilized product to demonstrate that the sterilization
process specification has been met. These data shall include at least the following:
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a) variables monitored during sterilization of final container(s), if appropriate;
b) variables monitored during sterilization of storage solution, if appropriate;
c) initial chemical concentration(s) and pH of liquid chemical sterilant;
d) parameters monitored during preparation of liquid chemical sterilant;
e) results of integrity tests on any filters used to sterilize solutions, if appropriate;
f) exposure time;
g) temperature during the exposure time;
h) results of environmental monitoring during aseptic transfer, if appropriate;
i) identities of personnel who are:
1) preparing storage solutions and liquid chemical sterilant solutions;
2) controlling the sterilization process; and
3) performing aseptic transfer, if appropriate;
j) numbers (or other unique identification) of products processed.
6.3 For each batch of medical devices subjected to liquid chemical sterilization, the following shall be examined for
the presence of viable microorganisms:
a) chemical sterilant solutions;
b) storage solutions, if applicable;
c) at least one of the following:
1) finished product;
2) product which has been rejected but subjected to the complete manufacturing process; or
3) isolated pieces of animal tissue, justified as being representative of the medical device, which have been
subjected to the complete manufacturing process.
6.4 For each batch of medical devices, a portion of either:
a) liquid chemical sterilant solution, or
b) liquid chemical sterilant solution remaining following the sterilization process
shall be challenged under the same conditions as the batch of medical devices by a carrier of the animal tissue
6
inoculated with a microorganism complying with ISO 11138-1 and containing at least 10 organisms with a known high
resistance to the sterilization process, as identified during performance qualification (see 5.3).
NOTE — When performing the test, appropriate precautions should be taken t
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