ISO 11737-3:2004
(Main)Sterilization of medical devices — Microbiological methods — Part 3: Guidance on evaluation and interpretation of bioburden data
Sterilization of medical devices — Microbiological methods — Part 3: Guidance on evaluation and interpretation of bioburden data
ISO 11737-3:2004 provides guidance on evaluating and interpreting the data generated during routine monitoring of the microbiological quality of medical devices. ISO 11737-3:2004 is not applicable to the use of bioburden data generated for establishing the extent of treatment to be applied in a sterilization process. ISO 11737-3:2004 is not applicable to microbiological data generated from sampling the environment in manufacturing areas.
Stérilisation des dispositifs médicaux — Méthodes microbiologiques — Partie 3: Lignes directrices sur l'évaluation et l'interprétation de données de charge biologique
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Standards Content (Sample)
INTERNATIONAL ISO
STANDARD 11737-3
First edition
2004-07-01
Sterilization of medical devices —
Microbiological methods —
Part 3:
Guidance on evaluation and interpretation
of bioburden data
Stérilisation des dispositifs médicaux — Méthodes microbiologiques —
Partie 3: Lignes directrices sur l'évaluation et l'interprétation de données
de charge biologique
Reference number
ISO 11737-3:2004(E)
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ISO 2004
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ISO 11737-3:2004(E)
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ISO 11737-3:2004(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
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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 11737-3 was prepared by Technical Committee ISO/TC 198, Sterilization of health care products.
ISO11737 consists of the following parts, under the general title Sterilization of medical devices —
Microbiological methods:
— Part 1: Estimation of population of microorganisms on products
— Part 2: Tests of sterility performed in the validation of a sterilization process
— Part 3: Guidance on evaluation and interpretation of bioburden data
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ISO 11737-3:2004(E)
Introduction
International standards for the validation and routine control of sterilization processes have been published
(ISO 11134, ISO 11135, ISO 11137, ISO 14160 and ISO 14937). These standards specify that the bioburden,
i.e. the population of microorganisms present on product, be estimated during validation and that the routine
control of the sterilization process include a programme of bioburden monitoring. These requirements are
specified because it is important that the microbiological quality of product presented for sterilization is
consistent over time, and that the level of microbiological contamination is as low as practicable taking into
account the nature of the raw materials, the product itself and the processes involved in manufacture.
ISO 11737-1 specifies requirements for the estimation of bioburden.
The natural microbial population on and/or in product items is the challenge to the sterilization process.
Bioburden estimations, performed as part of validation, provide information about this challenge. The results of
performing bioburden estimations may be used in the determination of the extent of treatment to be applied in
the sterilization process (see, for example, ISO 11137). However, such application of bioburden data is
particular to the method of sterilization and, therefore, is not considered in this part of ISO 11737.
The estimations performed as part of routine control are intended to detect changes in bioburden in terms of the
number of contaminating microorganisms and/or the types of microorganisms present. Bioburden data are an
element of the system of monitoring the effectiveness of controls applied to manufacturing processes and to the
environment in which medical devices are manufactured; as such, bioburden data are part of the quality records
within the quality management system (see ISO 13485). In the context of a quality management system,
bioburden estimations may be an element of one or more of the following:
— an overall environmental monitoring system;
— an assessment of the effectiveness of a cleaning process in removing microorganisms;
— a programme for monitoring a manufacturing process for product supplied non-sterile but for which a level of
microbiological cleanliness is specified;
— a programme of monitoring the microbiological quality of raw materials, components or packaging.
This part of ISO 11737 is intended to provide guidance only on the evaluation and interpretation of bioburden
data in routine control and monitoring. The guidance given here is additional to that provided in
ISO 11737-1:1995, Annex A.
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INTERNATIONAL STANDARD ISO 11737-3:2004(E)
Sterilization of medical devices — Microbiological methods —
Part 3:
Guidance on evaluation and interpretation of bioburden data
1Scope
This part of ISO 11737 provides guidance on evaluating and interpreting the data generated during routine
monitoring of the microbiological quality of medical devices.
This part of ISO 11737 is not applicable to the use of bioburden data generated for establishing the extent of
treatment to be applied in a sterilization process.
This part of ISO 11737 is not applicable to microbiological data generated from sampling the environment in
manufacturing areas.
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 11737-1:1995, Sterilization of medical devices — Microbiological methods — Part1: Estimation of
population of microorganisms on products
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 11737-1 apply.
NOTE The term bioburden as used in this document may include pre-sterilization count, viable count, or bioburden
estimate.
4 Origins of bioburden and bioburden control
4.1 Origins of bioburden
4.1.1 Contributors to bioburden include
— raw materials (of synthetic or natural origin),
— manufacturing of components (e.g. moulding, casting or hand cutting),
— assembly process (manual, automated or a combination of these),
— manufacturing environment,
— assembly/manufacturing aids (e.g. compressed air, water, lubricants),
— cleaning process, and
— packaging of finished products (manual or automated).
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ISO 11737-3:2004(E)
4.1.2 In some cases, the most significant contributor to product or component bioburden is a raw material.
Raw materials of natural origin often have a high bioburden exhibiting a great deal of variability. A raw material
of natural origin can also introduce microorganisms that generally are not present on medical devices. Synthetic
raw materials usually have lower and less variable bioburden. If the raw material can support microbial growth,
this can significantly influence the bioburden.
4.1.3 The method of manufacture of components can have an impact on their bioburden. The hand cutting of
material into components or the manual handling of materials contributes to bioburden and may increase
variability. Moulding under high temperature and pressure on the other hand can produce components that
have low bioburden. Bioburden on such moulded components is usually the result of handling or exposure to
the environment. If this is controlled, the bioburden will remain low with little variability.
4.1.4 Product and component handling during assembly and other production activities, such as inspection,
have been identified as being a major contributor to product bioburden. Automated assembly processes have
been shown to produce products with lower bioburden, and less variable bioburden than manual assembly
processes. Manual assembly results not only in higher bioburden but also in greater variability. If the assembly
process is complex, the bioburden can increase, due to the length of exposure to the manufacturing
environment and the number of steps in which bioburden could be introduced.
4.1.5 The manufacturing environment and the extent of control of that environment can have an impact on
bioburden. Prolonged exposure of components or products to an uncontrolled environment can be a significant
contributor to high levels of bioburden. If the manufacturing environment and practices do not provide barriers
between the product and an uncontrolled environment, the product bioburden can show shifts in numbers and
types (e.g. genus, and species or morphological state, such as vegetative versus spores) due to climatic and
seasonal changes. Work surfaces in the manufacturing environment can also accumulate microorganisms that
can be transferred to components and products during assembly.
4.1.6 Assembly aids, such as compressed gasses, water, lubricants, etc., can be a source of bioburden, and
their use can result not only in increased levels but also in large variability. If these assembly aids support
microbial growth, the level of bioburden and its variability can increase. A final cleaning step prior to packaging
can reduce both the overall level of bioburden and the variability. If the cleaning process leaves a residue in/on
the product, however, the opposite effect can occur, resulting in increased bioburden and variability.
4.1.7 Just as with automated assembly, automated packaging will contribute fewer organisms and there will be
less variability than with manual packaging. Packaging components of plastics or nonwoven synthetic materials
are generally not substantial contributors of bioburden. However, if paper products are part of the primary
package, they may have a higher bioburden than the product being packaged.
4.2 Nature of bioburden data
4.2.1 The examination of estimates of bioburden derived from a wide range of products illustrates the
variability of bioburden data. Estimates obtained from a group of items will vary within the group of items, and,
therefore, analyses of bioburden data generally use means. Clearly, these means may take high, intermediate
or low values, and mean values will vary over time. Furthermore, the types of microorganism that comprise the
bioburden can also vary.
4.2.2 A commonly observed characteristic of the frequency distributions of bioburden data is that distributions
are extremely skewed and frequently show extremely long tails. For low or intermediate bioburden data, the
modal value is zero. In these circumstances, the bioburden estimate is generally low but there may be
occasional high estimates, even though the control measures are effectively applied.
4.2.3 The extreme asymmetry of these skewed frequency distributions means that the established techniques
of quality control based on symmetric distributions are not always appropriate. If statistical analysis of bioburden
data is carried out, special statistical techniques may have to be developed for individual cases, either
a) using transformation techniques to make the distribution of the data symmetrical and applying standard
techniques, or
b) developing a new technique specifically suited to a skewed distribution.
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ISO 11737-3:2004(E)
4.3 Monitoring of bioburden
4.3.1 A bioburden monitoring programme does not control the bioburden on raw materials, components or
products. Generally, control is obtained through implementation of appropriate operational measures. A
monitoring programme is a means of assessing the effectiveness of the control measures in place. In order to
implement effective measures, it is necessary to know the bioburden contributors in a process. A bioburden
monitoring programme that identifies the major contributors to bioburden can provide meaningful data on where
to apply control measures. Once the control measures are in place, their continued effectiveness can be
confirmed by periodic monitoring of products and/or components.
4.3.2 The monitoring programme should inclu
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