BS EN ISO 14937:2009

BS EN ISO 14937:2009 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

BS EN ISO 14937 is the standard that specifies the general requirements for the characterization of a sterilizing agent and for the development, validation and routine monitoring and control of a sterilization process for medical devices.

Although BS EN ISO 14937’s scope is limited to medical devices, the requirements it specifies can also be applied to sterilization processes for other health care products.

BS EN ISO 14937 applies to sterilization processes in which microorganisms are inactivated by physical and/or chemical means. It is intended to be applied by process developers, manufacturers of sterilization equipment, manufacturers of medical devices to be sterilized, and organizations responsible for sterilizing medical devices.

BS EN ISO 14937 specifies the elements of a quality management system (QMS), that are necessary to assure the appropriate characterization of the sterilizing agent, development, validation and routine monitoring and control of a sterilization process.

• 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
• For manufacturers and users of sterilization processes in health care settings for which a specific International Standard does not exist
• As a framework for the preparation or revision of standards for specific sterilization processes.

BS EN ISO 1493 draws attention to the standards for quality management systems (see BS EN ISO 13485) that control all stages of production or reprocessing of medical devices. National and/or regional regulations for the provision of medical devices might require the implementation of a full quality management system and the assessment of that system by a third party.

A sterile medical device is one that is free of viable microorganisms. International Standards that 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) could, prior to sterilization, have microorganisms on them, albeit in low numbers. Such medical devices are non-sterile.

The purpose of sterilization is to inactivate the microbiological contaminants and thereby transform the nonsterile medical devices into sterile ones.

The kinetics of inactivation of a pure culture of microorganisms by physical and/or chemical agents used to sterilize medical devices generally can best be described by 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 might 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 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.

BS EN ISO 14937 describes requirements that, if met, will provide a sterilization process with appropriate microbicidal activity intended to sterilize medical devices. Furthermore, compliance with the requirements ensures that the sterilization process 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 a medical device 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 and particular requirements for quality management systems for medical device production are given in ISO 13485. The standards for quality management systems recognise 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 a processed medical device is sterile and, in this regard, suitable for its intended use. Attention is also given to a number of factors including:

• The microbiological status of incoming raw materials and/or components
• The validation and routine control of any cleaning and disinfection procedures used on the medical device
• The control of the environment in which the medical device 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 medical device is packaged
• The conditions under which the medical device is stored.

The type of contamination on a medical device to be sterilized varies, and this influences the effectiveness of a sterilization process. Medical devices that have been used in a health care setting and that are being presented for resterilization in accordance with the manufacturer's instructions (see ISO 17664) should be regarded as special cases. There is the potential for such medical devices 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 has to be given to the validation and control of the cleaning and disinfection processes used during reprocessing.

The development, validation and routine control of a sterilization process comprise a number of discrete but interrelated activities, for example, calibration, maintenance, product definition, process definition, installation qualification, operational qualification and performance qualification.

While the activities required by BS EN ISO 14937 have been grouped together and are presented in a particular order, this standard does not require that the activities be performed in the order that they are presented. The activities required are not necessarily sequential, as the programme of development and validation can be iterative. The responsibility for carrying out the activities required by BS EN ISO 14937 will vary from case to case.

• 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
• For manufacturers and users of sterilization processes in health care settings for which a specific International Standard does not exist
• As a framework for the preparation or revision of standards for specific sterilization processes.

Relationship between BS EN ISO 14937 and the Essential Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices

This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 90/385/EEC on active implantable medical devices.

This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 93/42/EEC on medical devices.

This European Standard has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association to provide a means of conforming to Essential Requirements of the New Approach Directive 98/79/EC on in vitro diagnostic medical devices.

• Scope
• Inclusions
• Exclusions
• Normative references
• Terms and definitions
• Quality management system elements
• Documentation
• Management responsibility
• Product realization
• Measurement, analysis and improvement — Control of non-conforming product
• Sterilizing agent characterization
• Sterilizing agent
• Microbicidal effectiveness
• Effects on materials
• Safety and the environment
• Process and equipment characterization
• Process characterization.
• Equipment characterization
• Product definition
• Process definition
• Validation
• Installation qualification
• Operational qualification
• Performance qualification
• Review and approval of validation
• Routine monitoring and control
• Product release from sterilization
• Maintaining process effectiveness
• Recalibration
• Maintenance of equipment
• Requalification
• Assessment of change
• Factors to be considered in selection of microorganisms for demonstrating microbicidal effectiveness
• Approach 1 — Process definition based on inactivation of the microbial

  population in its natural state

• Approach 2 — Process definition based on inactivation of reference

  microorganisms and knowledge of bioburden

• Approach 3 — Conservative process definition based on inactivation of reference microorganisms
• Guidance on application of this International Standard

  Bibliography