Standards Development

Scope

Specifies the requirements and the relevant tests for sterilizers intended to be used for the terminal sterilization of health care products (medical devices or medicinal products) presented as aqueous liquid in sealed containers. The container can be rigid, semi rigid or flexible. The sterilizing agent, moist heat, is created internally from the product, heating being achieved by use of saturated steam, mixtures of steam and a pressure ballasting non-condensing gas such as air or super-heated water in the sterilizer chamber. The sterilizers can be used in both a health care and industrial setting. This standard does not apply to sterilizers using saturated steam for the sterilization of the surfaces of medical devices or sterilizers used in laboratories.

NOTE 1 Sterilizers using saturated steam for sterilizing the surfaces of medical devices are covered by EN 285 and EN 13060. Laboratory sterilizers are covered by some national standards.

NOTE 2 Sterilizers conforming to NWIP ISO XXXXX can also be used for the sterilization of other aqueous liquid in sealed containers such as veterinary products or some foodstuffs.

Note 3 Sterilizers conforming to NWIP ISO XXXXX can also be used for the sterilization of a contained product enclosed within a sterile barrier system conforming to the EN ISO 11607 series of standards.

Purpose

Many health care products consist of sterile aqueous liquids packaged in sealed containers. These products, often pharmaceutical in nature (i.e. medicinal products) range in size from small volume (eg 1ml) sealed glass ampoules to large volume (eg >1 litre) sealed plastic bottles or flexible pouches. Examples of products are water for injection for the reconstitution of freeze-dried injectable products or sterile water for irrigation for irrigating body cavities during surgery or rinsing medical devices prior to implantation or use in surgery. Such products are usually produced in an industrial setting but in some countries, health care settings, such as larger hospitals providing services to a significant geographic area, can also have production facilities for sterile fluids. Wherever produced, sterile aqueous liquids in sealed containers, which can be rigid, semi-rigid or flexible, require the use of a sterilizer. Such sterilizers usually employ high temperature, pressurised saturated steam, mixtures of saturated steam and a pressure ballasting non-condensing gas such as air or superheated water in order to heat the contained product to sterilizing temperatures.

ISO/TS 22421:2021, Sterilization of health care products – Common requirements for sterilizers for terminal sterilization of medical devices in health care facilities was developed within ISO/TC 198 in order to create a generic standard for any sterilizer used for the terminal sterilization of medical devices. During development, many national and regional standards and guidance documents were consulted in order to ensure the content of the new standard was comprehensive reflecting the content of currently published documents. Furthermore, during development and in order to respect the various opinions and comments expressed, clauses were made sufficiently generic to allow a degree of interpretation by document users. Upon completion, it was generally agreed that this new technical specification could form the basis of a series of documents covering sterilizers for specific sterilization modalities, thereby acting as a template for the future development of specific sterilizer standards. In the United Kingdom, the British Standards Institution published BS 3970 Part 2 in 1991 which covered steam sterilizers for aqueous fluids in sealed rigid containers. As part of the normal review process, BSI decided to place BS 3970-2 into revision. The BSI technical committee CH/198 (Sterilization and Associated Equipment and Processes) is responsible for mirroring the work of ISO/TC 198 (Sterilization of Health Care Products). The revision of BS 3970 therefore fell within the remit of CH/198. CH/198 is constituted from many organisations and individuals who have an interest in the sterilization of health care products. A subcommittee was established from the membership of CH/198 who had a particular interest in the sterilization of contained products. It was agreed at the onset of the process that the revision of BS 3970 should follow the format of ISO/TS 22421. However, after several meetings it became clear that the developing standard spanned a variety of application areas and had an international “flavour”. Therefore, a recommendation was made to CH/198 that the new document should be submitted to ISO as an NWIP.

Sterilizers used for the terminal sterilization of aqueous liquid containing health care products in sealed containers are used both in health care and industrial settings. Such sterilizers might be used in a large hospital which has a sterile fluids production unit associated with the pharmacy department. Similarly such sterilizers are used extensively within the pharmaceutical and biotechnology industries where aqueous based sterile pharmaceuticals are produced on a large scale. In the medical device industry combination products can also be found. An example might be disposable contact lenses immersed in an aqueous carrier liquid sealed in an extruded plastic container. Unlike sterilizers in which the steam entering the chamber eventually forms the sterilizing agent, moist heat (saturated steam sterilizers), the steam (or mixtures thereoff) used in contained product sterilizers acts as a heating medium which heats the aqueous liquid sealed within the container to a suifficiently high temperature to create the sterilizing agent internally. Whilst there are similarities to saturated steam sterilizers which are covered by national and regional standards (e.g. EN 285 on large steam sterilizers), contained product sterilizers are different in terms of construction and operation thus warranting the need for a separate standard.

SO/TC 198 has working groups covering a variety of sterilization and disinfection modalities. Whilst originally established to deal with standards for the development, validation and routine control of sterilization, it has now evolved into a technical committee which deals with both processes (e.g. ISO 14937) and equipment (e.g. ISO/TS 22421). ISO/TC 198/WG 3 has thus far been responsible for the development of ISO 17665 Moist heat sterilization. However, there are experts who have experience in specifying, manufacturing, validating and routinely managing moist heat sterilizers and so this would be an ideal working group to develop the new work item proposal. The publication of a standard for contained product moist heat sterilizers would undoubtedly complement the current moist heat sterilization process standard, ISO 17665.

Market Relevance

Sterilizers used for the terminal sterilization of health care products containing aqueous liquid in sealed containers are used globally in both health care and industrial settings yet there are, to date, no internationally agreed standards for such sterilizers. ISO/TS 22421 can be used as a template for locally produced standards and guidance. Similarly ISO 17665 contains sections which deal with requirements for equipment characterisation and validation (installation and operational qualification). The national and regional Pharmacopoeias (e.g. United States Pharmacopoeia, European Pharmacopoeia) contain monographs very briefly covering sterilizers as does the European guidance document, Rules and Guidance for Pharmaceutical Manufacturers and Distributors, 2022. Within the pharmaceutical and biotechnology sectors, there are a number of guidance documents published by professional associations which are often referred to by industry (e.g. Parenteral Drug Association guidance, TR 48 Moist heat sterilizer systems, design, commissioning, operation, qualification and maintenance). Similarly within individual corporate bodies, design departments will specify sterilizers in very fine detail. The publication of an international standard for sterilizers used for the terminal sterilization of health care products containing aqueous liquid in sealed containers would provide a global commonly agreed approach both for manufacturers and users of such sterilizers.

Stakeholder Engagement

During the revision of BS 3970 within BSI’s CH/198 committee and subsequent development of NWIP XXXXX, representation from the health care sector, the pharmaceutical and biotechnology industries and the manufacturing organisations was sought, several of whom had direct representation on the responsible working group. Many of the members belonged to larger corporate bodies who have international operations. Whilst further direct stakeholder engagement could take place, the authors of this Form 4 NWIP do not believe that additional information above and beyond that outlined above would change the overall impression that a new standard is required. The ballot on the Form 4 enquiry will ascertain interest at the national standards bodies level.