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This document was prepared by Technical Committee ISO/TC 198, Sterilization of health care products, in collaboration with the European Committee for Standardization (CEN) Technical Committee CEN/TC 204, Sterilization of medical devices, in accordance with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).

This second edition cancels and replaces the first edition (ISO 11137-1:2006), which has been technically revised.

The main changes are as follows:

addition of ISO 13004 as a normative reference;
addition of ISO/ASTM 52628 as a normative reference for dosimetry in radiation processing and alignment of terminology across the document to ASTM standards terminology;
update of Clause 4 to align with ISO/TC 198 documents;
increase of the allowable limits above which the potential induced radioactivity shall be assessed to 11 MeV for electrons and 7,5 MeV for X-rays (see 5.1.2);
addition of a requirement to ensure that failure of a control function does not lead to a failure in recording process parameters such that an ineffective process appears effective (see 6.1);
simplification of content on transference of verification dose or sterilization dose based on published data that demonstrates that differences in operating conditions of the two radiation sources have no effect on microbicidal effectiveness for product that does not promote microbial growth (see 8.4.2);
clarification on the use of dose measurements and the recording of process variables for process control (see 10.6 and 10.7);
clarification has been provided on the allowable interval of time for quarterly dose audits, allowing for an interval of four months provided there are four dose audits per year (see 12.1.2);
addition of references for all VD_max^SD dose levels contained in both ISO 11137-2 and ISO 13004 (see 8.2.2 and 12.1.2);
additional information has been included on bioburden determination for products with very low bioburden (see 12.1.2.2 and A.12.1.2.2);
addition of guidance related to new or modified normative content;
addition of references to the Bibliography.

A list of all parts in the ISO 11137 series can be found on the ISO website.

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Introduction

A sterile medical device is one that is free of viable microorganisms. International Standards, which specify requirements for validation and routine control of sterilization processes, require, when it is necessary to supply a sterile medical device, 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 management systems (see, for example, ISO 13485) can have microorganisms on them prior to sterilization. Such medical devices are non-sterile. The purpose of sterilization is to inactivate microbiological contaminants and thereby transform the non-sterile medical devices into sterile ones.

The kinetics of inactivation of a pure culture of microorganisms by either physical or chemical agents, or both, used to sterilize medical devices can be described as an exponential relationship between the number 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 can 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 microorganisms exist during treatment. It follows that the sterility of any one medical device in a population subjected to sterilization processing cannot be guaranteed and the sterility of a processed population is defined in terms of the probability of there being a viable microorganism present on a medical device.

This document describes requirements that, if met, will provide a radiation sterilization process, intended to sterilize medical devices. Furthermore, conformance with the requirements ensures that this activity is both reliable and reproducible so that predictions can be made, with reasonable confidence, that there is a low level of probability of there being a viable microorganism present on product after sterilization. Specification of this probability is a matter for regulatory authorities and can vary from country to country (see, for example, EN 556-1 and ANSI/AAMI ST67).

Generic requirements of the quality management system for design and development, production, installation and servicing are given in ISO 9001, while specific requirements for quality management systems for medical device production are given in ISO 13485. The standards for quality management systems recognize that, for certain processes used in manufacturing, 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 is monitored routinely and the equipment is maintained.

Exposure to a properly validated, accurately controlled sterilization process is not the only factor associated with the provision of reliable assurance that the medical devices are sterile and suitable for its intended use. Attention is therefore given to a number of considerations, including:

the microbiological quality (microorganism numbers and characterization) of incoming raw materials and components;
the validation and routine control of any cleaning and disinfection procedures used on the product;
the control of the environment in which the product is manufactured, assembled and packaged;
the control of equipment and processes;
the control of personnel and their hygiene;
the manner and materials in which the product is packaged;
the conditions under which product is stored.

This document describes the requirements for ensuring that the activities associated with the process of radiation sterilization are performed properly. These activities are described in documented work programmes designed to demonstrate that the irradiation process will consistently yield sterile medical devices on treatment with doses falling within the predetermined limits.

The requirements are the normative parts of this document with which conformance is claimed. The guidance given in Annex A is informative and is not provided as a checklist for auditors. The guidance provides explanations and methods that are an example of suitable means for conforming with the requirements. Methods other than those given in the guidance may be used, if they are effective in achieving conformance with the requirements of this document.

The development, validation and routine control of a sterilization process comprise a number of discrete but interrelated activities, e.g. calibration, maintenance, product definition, process definition, installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ). The activities required by this document do not need to be performed in the order in which they are presented. The activities required are not necessarily sequential, as the programme of development and validation may be iterative. It is possible that performing these different activities will involve a number of separate individuals or organizations, or both, each of whom undertake one or more of these activities. This document does not specify the particular individuals or organizations to carry out the activities.

1 Scope

1.1

This document specifies requirements for the development, validation and routine control of a radiation sterilization process for medical devices.

NOTE Although the scope is limited to medical devices, this document can be applicable to other products and equipment.

This document covers radiation processes employing irradiators using:

the radionuclide ⁶⁰Co or ¹³⁷Cs;
a beam from an electron generator; or
a beam from an X-ray generator.

1.2

This document is not applicable to processes for inactivating viruses or the causative agents of spongiform encephalopathies, such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease.

NOTE For information on such processes, see ISO 22442-1, ISO 22442-2, ISO 22442-3, ISO 13022 and ICH Q5A.

1.2.1

This document does not specify requirements for designating a medical device as sterile.

NOTE Regional and national requirements can designate medical devices as sterile. See, for example, EN 556-1 or ANSI/AAMI ST67.

1.2.2

This document does not specify a quality management system for the control of all stages of production of medical devices.

NOTE It is not a requirement of this document to have a complete quality management system during manufacture, but the elements of a quality management system that are the minimum necessary to control the sterilization process are normatively referenced at appropriate places in the text (see, in particular, Clause 4). Attention is drawn to the standards for quality management systems (see ISO 13485) that control all stages of production of medical devices, including the sterilization process. Regional and national regulations for the provision of medical devices can require implementation of a complete quality management system and the assessment of that system by a third party.

1.2.3

This document does not require that biological indicators be used for validation or monitoring of radiation sterilization, nor does it require that a pharmacopoeial test for sterility be carried out for product release.

1.2.4

This document does not specify requirements for occupational safety associated with the design and operation of irradiation facilities.

NOTE Regulations on safety requirements for occupational safety related to radiation can exist in some countries.

1.2.5

This document does not specify requirements for the sterilization of used or reprocessed devices.

2 Normative references

3 Terms and definitions

4 General

4.1

4.2

4.3

5 Sterilizing agent characterization

5.1 Sterilizing agent

5.2 Microbicidal effectiveness

5.3 Material effects

5.4 Environmental considerations

6 Process and equipment characterization

6.1 Process

6.2 Equipment

7 Product definition

7.1

7.2

7.3

7.4

7.5

8 Process definition

8.1 Establishing the maximum acceptable dose, D_max,acc

8.2 Establishing the sterilization dose, D_ster

8.3 Specifying the maximum acceptable dose and the sterilization dose

8.4 Transference of maximum acceptable, verification or sterilization dose between radiation sources

9 Validation

9.1 Installation qualification (IQ)

9.2 Operational qualification (OQ)

9.3 Performance qualification (PQ)

9.4 Review and approval of validation

10 Routine monitoring and control

10.1

10.2

10.3

10.4

10.5

10.6

10.7

10.8

10.9

10.10

10.11

11 Product release from sterilization

11.1

11.2

12 Maintaining process effectiveness

12.1 Demonstration of continued effectiveness

12.2 Recalibration

12.3 Maintenance of equipment

12.4 Requalification of equipment

12.5 Assessment of change

Bibliography

ISO 11137-1:2025

Sterilization of health care products. Radiation - Requirements for the development, validation and routine control of a sterilization process for medical devices

Current

Published:

2 Apr 2025