ISO/DIS 19253:2026(en)
ISO/TC 198
Secretariat: ANSI
Date: 2025-12-05
Sterilization of health care products — Moist heat — Requirements for sterilizers used for the terminal sterilization of aqueous liquid in sealed containers
© ISO 2026
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Contents
5 Equipment design and construction 9
5.1.2 Over pressure protection devices (OPPD) 10
5.1.3 Over temperature protection devices 10
5.1.4 Door release safety system 11
5.1.5 Chamber empty protection system. 11
5.2.3 Design of water dispersion systems within the chamber 12
5.2.7 Uniformity of conditions 16
5.2.8 Ancillary equipment and components 16
6 Indicating, monitoring, controlling and recording 22
6.3 Control and monitoring system 23
7 Service and local environment 32
7.2 Sterilizing agent and sterilant 33
8.1 Electromagnetic emissions 35
10 Performance and assessment 37
10.3 Attainment of conditions - Thermometric 38
10.4 Microbiological performance 41
11 Information to be supplied 41
11.2 Information to be available prior to purchase 42
11.3 Post delivery information to be provided 43
Annex A (informative) Background to the development of ISO 19253 47
Annex B (informative) Illustrations of the interrelationship between control and recording 49
Annex E (informative) Verification of the sterilizer’s F0 value accumulation system (if fitted) 62
Annex F (normative) Test methods and reference loads for contained product sterilizers 66
Annex H (normative) Test instrumentation 82
Annex I (informative) Test methods for determining steam quality 87
Foreword
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The procedures used to develop this document and those intended for its further maintenance are described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the different types of ISO documents should be noted. This document was drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
ISO draws attention to the possibility that the implementation of this document may involve the use of (a) patent(s). ISO takes no position concerning the evidence, validity or applicability of any claimed patent rights in respect thereof. As of the date of publication of this document, ISO had not received notice of (a) patent(s) which may be required to implement this document. However, implementers are cautioned that this may not represent the latest information, which may be obtained from the patent database available at www.iso.org/patents. ISO shall not be held responsible for identifying any or all such patent rights.
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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 102, Sterilizers and associated equipment for processing of medical devices, in accordance with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).
A list of all parts in the ISO 19253 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A complete listing of these bodies can be found at www.iso.org/members.html.
Introduction
Sterilizers designed to deliver moist heat sterilization processes are capable of reliable and effective inactivation of microbiological contaminants to provide sterile medical products. Validated moist heat sterilization processes can be utilized to sterilize porous loads or contained medical products (see ISO 17665). However, the moist heat sterilization processes and sterilizers used to deliver these processes can differ significantly for these two product types.
While saturated steam is used to sterilize porous load medical products, the heating medium (moist heat) used for contained products can consist of saturated steam, non-saturated steam, a mixture of steam and air or an inert gas, a mixture of steam and a pressurized water spray or water immersion. Saturated steam sterilization processes employ the use of a passive or active air removal stage followed by sterilization with saturated steam that directly contacts the product providing the required energy for heating and moisture for effective microbial inactivation. Conversely, sterilization of contained fluid products can be accomplished with energy from a heating medium containing steam or heated water that is transferred through the sealed product container materials with the sterilizing agent, moist heat, being generated from the heated aqueous formulation. Additionally, an overpressure ballasting, non-condensing gas such as air or nitrogen is often required to protect the integrity of the container closure system for contained products. Due to these and other sterilization process differences, this standard was developed to address the specific requirements for contained product sterilizers. This document is based on the content, format and structure of ISO/TS 22421 and provides specific requirements for the sterilizer used for the sterilization of medical products presented as aqueous formulations in sealed containers. The requirements for saturated steam sterilizers used for porous loads of medical products are covered in other standards such as EN 285.
Sterilizers conforming to the requirements of this document:
— can be used in a health care facility or in an industrial setting for sterilizing contained products such as pharmaceuticals, veterinary products or other aqueous sterile products in sealed containers;
— can be used to sterilize contained medical products including aqueous liquids, gels, a solution of a solute in water, a colloidal dispersion, a suspension of a solid substrate in water, or an oil in water emulsion;
— can be used to process sealed containers which can be rigid (e.g. glass ampoules, vials or bottles), semi-rigid (e.g. polypropylene bottles or syringes), or flexible intravenous infusion bags (e.g. polyvinyl chloride bags);
— can be designed to provide a sterilization cycle in which:
— the load is heated to a specified temperature and held for a specified time, then cooled;
— the load is exposed to specified parameters for the heating period, exposure period (i.e. time at a specified temperature or an accumulated F0 value), and a cooling period to meet physical microbiological lethality values i.e. a specified F0 value and FBIOLOGICAL requirements to support the required sterility assurance level (SAL) for the medical products;
NOTE For information about FBIOLOGICAL see ISO 17665.
— are designed for batch production but not for processes in which the product continually passes through a processing environment;
— can be designed so that the load remains static throughout the sterilization process or can provide a means of agitating the load by, for example, shaking or rotating, to enable the container contents to be mixed;
— can be of any usable chamber space.
Some sterilizers are designed to process vented containers which are those which are not sealed but rather allow free gaseous exchange in order to avoid pressure build up inside the container. Whilst sterilizers conforming to this document are designed for the terminal sterilization of sealed containers a process can be implemented in such a sterilizer to process vented containers.
The delivery of a validated and accurately controlled sterilization process is enabled by the use of sterilizing equipment that is designed, constructed, installed and qualified to deliver the sterilization process safely and reproducibly. Use of a sterilizer meeting the requirements of this standard and conformance with ISO 17665 for the development, validation and routine control of sterilization processes ensures the delivery of a reliable, reproducible, and accurately controlled sterilization process that can provide the required Sterility Assurance Level (e.g. ≤1 x 10-6) for contained medical products.
The tests described in this standard are reference tests intended for use in demonstrating conformity with the specified performance requirements. They can be used in type tests, works tests, in validation and re-validation tests, or in periodic and routine tests carried out by the user.
Sterilizers conforming to this document can be designed to perform separate contained product sterilization cycles and saturated steam sterilization cycles for porous products. In such cases, the requirements specified in this document and a standard which includes sterilizers for saturated steam sterilization processes (e.g. EN 285) should be considered.
This document does not specify requirements for equipment for inactivating the causative agents of spongiform encephalopathies such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease.
NOTE Specific regulations have been produced in particular countries for the processing of materials potentially contaminated with these agents. See also ISO 22442-1, ISO 22442-2 and ISO 22442-3.
Background to the development of this document is provided in Annex A.
Sterilization of health care products — Moist heat — Requirements for sterilizers used for the terminal sterilization of aqueous liquid in sealed containers
1.0 Scope
This document specifies the requirements and tests for moist heat sterilizers intended to be used for the terminal sterilization of batch produced health care products presented as aqueous liquid in sealed containers.
The aqueous liquid which the sterilizer is designed to process can be:
a) liquid water or solutions in which a solute is dissolved;
b) suspensions in which solid particles are suspended in an aqueous solvent;
c) oil in water emulsions in which oil droplets are suspended in an aqueous solvent.
The container which the sterilizer is designed to process can be rigid, semi rigid, or flexible and constructed from, for example, glass or polymeric materials.
The sterilizer is designed to operate with a moist heat heating medium introduced into or created within the chamber, which can consist of:
1. saturated steam;
2. non-saturated steam;
3. a mixture of steam and pressurized water spray; or
4. water immersion.
An over pressurising non-condensable gas such as air or nitrogen introduced into the chamber can be used to prevent container deformation or bursting and protect the integrity of the container closure system for steam-air mixtures, heated water as a spray or water immersion processes.
This document applies to sterilizers designed to allow the load to remain static throughout the sterilization cycle and sterilizers that have a means by which the load is mechanically agitated by, for example, shaking or rotation.
The sterilizer can be used in a health care facility or an industrial setting.
The reference loads described in this document are representative of a small load of low thermal capacity and a large load of high thermal capacity which can be used for establishing the basic performance of the sterilizer. The performance of the sterilizer when processing production loads will be established during validation using specified loads. Requirements for the development, validation and routine control of moist heat sterilization processes is described in ISO 17665.
This document is intended for sterilizers which are designed to process a defined load of product and not for those which are designed to sterilize a continuous flow of product through a processing environment.
Sterilizers conforming with this document can also be used for the sterilization of veterinary products.
Sterilizers conforming with this document can also be used for the sterilization of a contained product enclosed within a sterile barrier system conforming to the ISO 11607 series.
This document is not intended to be retrospectively applied to pre-existing sterilizer equipment.
NOTE 1 The sterilizing agent, moist heat, is produced within the contained product by use of a heating medium.
NOTE 2 Sterilizers using saturated steam for sterilizing the surfaces of medical devices are covered by other standards, e.g. EN 285, EN 13060, ANSI/AAMI ST8, ANSI/AAMI ST55, JIS T 7322 and JIS T 7324. Some moist heat / steam sterilizers can be designed to provide both saturated steam sterilization processes and contained fluid sterilization processes.
2.0 Normative references
The following documents are referred to in the text in such a way that some or all of their content constitutes requirements 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 228‑1:2000, Pipe threads where pressure-tight joints are not made on the threads — Part 1: Dimensions, tolerances and designation
ISO 3746:2010, Acoustics — Determination of sound power levels and sound energy levels of noise sources using sound pressure — Survey method using an enveloping measurement surface over a reflecting plane
ISO 4126‑1:2013+A2:2019, Safety devices for protection against excessive pressure — Part 1: Safety valves
ISO 8362‑1, Injection containers and accessories — Part 1: Injection vials made of glass tubing
ISO 8362‑2, Injection containers and accessories — Part 2: Closures for injection vials
ISO 8362‑3, Injection containers and accessories — Part 3: Aluminium caps for injection vials
ISO 8536‑1, Infusion equipment for medical use — Part 1: Infusion glass bottles
ISO 8573‑1, Compressed air — Part 1: Contaminants and purity classes
ISO 11138‑3, Sterilization of health care products — Biological indicators — Part 3: Biological indicators for moist heat sterilization processes
ISO 13408‑2:2018, Aseptic processing of health care products — Part 2: Sterilizing filtration
ISO 17665:2024, Sterilization of health care products — Moist heat — Requirements for the development, validation and routine control of a sterilization process for medical devices
ISO 20417, Medical devices — Information to be supplied by the manufacturer
IEC 60204‑1:2016+A1:2021, Safety of machinery — Electrical equipment of machines — Part 1: General requirements
IEC 60584‑1:2013, Thermocouples EMF specifications and tolerances
IEC 60751:2022, Industrial platinum resistance thermometers and platinum temperature sensors
IEC 61010‑1:2010+A1:2019, Safety requirements for electrical equipment for measurement, control, and laboratory use — Part 1: General requirements
IEC 61010‑2-040:2020, Safety requirements for electrical equipment for measurement, control, and laboratory use — Part 2-040: Particular requirements for sterilizers and washer-disinfectors used to treat medical materials
IEC 61326‑1:2020, Electrical equipment for measurement, control and laboratory use — EMC requirements — Part 1: General requirements
IEC 62828‑1, Reference conditions and procedures for testing industrial and process measurement transmitters — Part 1: General procedures for all types of transmitters
3.0 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 17665:2024 and ISO/TS 22421 and the following apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https://www.iso.org/obp
— IEC Electropedia: available at https://www.electropedia.org/
3.1
access device
means by which entry to restricted parts of equipment is controlled
Note 1 to entry: This can be by dedicated key, code, or tool.
Note 2 to entry: There is likely to be more than one access device all of which can be different depending on function.
Note 3 to entry: The equipment can be software in which case the access device can be a code.
[SOURCE: ISO 11139:2018, 3.4, modified — The term “achieved” has been replaced by “controlled” and Notes 2 and 3 to entry were added.]
3.2
aqueous liquid
liquid water or solutions in which liquid water is the solvent into which a solute is dissolved, is the fluid in which solids are suspended or is the aqueous phase of an oil in water emulsion in which oil droplets are emulsified.
EXAMPLE Water for injection, normal saline solution, sterile intravenous suspension, total parenteral nutrition emulsions.
3.3
contained product sterilization
<moist heat sterilization> validated process where indirect contact of a moist heat heating medium on the external surfaces of contained product is used to create moist heat internally to achieve the specified requirements for sterility within the contained product
Note 1 to entry: Often referred to as “aqueous liquid sterilization.”
[SOURCE: ISO 11139:2018/Amd 1:2024, 3.332, modified — The term “moist heat” added has been added to the definition and “aqueous” has been added to Note 1 to entry.]
3.4
cooling medium
fluid used during an operating cycle to remove thermal energy from a load of contained product
Note 1 to entry: The cooling medium can be a flow of cooled air, a cooled water spray or a body of cooled water in which product is immersed.
3.5
cooling period
time elapsed after the exposure period when the load of contained product is cooled to a specified temperature
Note 1 to entry: The specified temperature is chosen so as not to create a thermal hazard when the load is removed from the chamber.
3.6
double-ended
having separate doors for loading and unloading in separate areas
Note 1 to entry: In some settings a sterilizer can be double-ended without being loaded and unloaded in separate areas.
[SOURCE: ISO 11139:2018, 3.92, modified — Note 1 to entry added.]
3.7
equilibration time
period between the attainment of defined sterilization process parameters at the reference measurement point and the attainment of the specified sterilization process parameters at all points within the load
Note 1 to entry: For the purposes of this document the process parameter to which this definition refers is temperature.
Note 2 to entry: For the purposes of this document the equilibration time only relates to those contained product sterilization processes which employ an operating cycle which heats the load to a specified sterilization temperature, holds it at that temperature for a specified time and then cools it.
[SOURCE: ISO 11139:2018, 3.105, modified — Notes to entry added.]
3.8
exposure period
<moist heat sterilization> time elapsed during the sterilization cycle when specified temperature(s) are maintained within defined ranges determined to be necessary to achieve the specified microbial lethality to support the required Sterility Assurance Level for the load of contained product
3.9
F0 value
measure of microbiological lethality delivered by a moist heat sterilization process expressed in terms of the equivalent time, in minutes, at a temperature of 121,1 °C with reference to microorganisms with a z value of 10 °C
[SOURCE: ISO 11139:2018, 3.113.1, modified — 10 K was replaced by °C (by convention, z value is expressed in °C).]
3.10
heating medium
fluid used during an operating cycle to transfer thermal energy to a load of contained product
Note 1 to entry: The heating medium can be saturated steam, steam-air mixtures, a heated water spray or a body of heated water in which product is immersed.
3.11
heating period
time elapsed from the introduction of the heating medium into the chamber to the attainment of a specified temperature(s) within the chamber or contained product within the load
Note 1 to entry: the specified temperature can be a defined sterilization temperature or a temperature when the automatic controller begins to accumulate F0 values.
3.12
holding time
<moist heat sterilization> period for which the temperatures at the reference measurement point and at all points within the load are continuously within the sterilization temperature band
Note 1 to entry: For the purposes of this document in addition to the load other fluids within the chamber are included in the definition e.g. cooling fluid, ballasting gas.
Note 2 to entry: For the purposes of this document the holding time only relates to those contained product sterilization processes which employ an operating cycle which heats the load to a specified sterilization temperature, holds it at that temperature for a specified time and then cools it.
[SOURCE: ISO 11139:2018/Amd 1:2024, 3.133.1, modified — Notes to entry added.]
3.13
load surrogate device
container filled with liquid into which a heat penetration probe is inserted providing temperature data to the automatic controller allowing control and monitoring of the sterilization cycle and calculation of F0 values
3.14
locked, door
condition in which the (a) chamber door is closed, that the securing mechanisms are in place, that the door is firmly sealed against the mating surface and that the door interlocks are activated and indicate to the automatic controller that the operating cycle can commence
3.15
maximum allowable working pressure
MAWP
maximum pressure to which a component is designed to be subjected to and which is the basis for determining the strength of the component under consideration
Note 1 to entry: The component can be the chamber.
[SOURCE: ISO 13985:2006, 3.10]
3.16
maximum permissible working pressure
MPWP
the maximum gauge pressure at which the vessel may be operated
Note 1 to entry: The maximum permissible working pressure is stipulated in the certificate of compliance issued by the manufacturer. It is to be not greater than the Maximum Allowable Working Pressure and can be varied during the working life of the vessel.
3.17
plateau period
equilibration time plus the holding time
Note 1 to entry: For the purposes of this document the plateau period only relates to those contained product sterilization processes which employ an operating cycle which heats the load to a specified sterilization temperature, holds it at that temperature for a specified time and then cools it.
[SOURCE: ISO 11139:2018, 3.195, modified — Note 1 to entry added.]
3.18
process variable
chemical or physical attribute within a cleaning, disinfection, packaging, or sterilization process, changes in which can alter its effectiveness
Note 1 to entry: For the purposes of this document process variables are conditions within a sterilization process, changes in which alter microbicidal effectiveness i.e. exposure time and temperature in the presence of moist heat.
[SOURCE: ISO 11139:2018, 3.213, modified — Note 1 to entry added and examples deleted.]
3.19
product cold spot
location or area within a health care product that receives the lowest lethality during a thermal sterilization cycle
Note 1 to entry: This can be the lowest accumulated lethality, e.g. F0 value, or the shortest time at the lowest temperature.
Note 2 to entry: The reproducibility of the product cold spot can be established during validation. See ISO 17665.
3.20
reference measurement point
location of the sensor(s) controlling the operating cycle
Note 1 to entry: The reference measurement point can be at more than one location and can change during an operating cycle depending if control is by F0 value or by temperature, pressure or a combination of the two changing at a specific stage(s) of the operating cycle.
[SOURCE: ISO 11139:2018, 3.227, modified — Sensor has been made plural and the Note 1 to entry added.]
3.21
response time
τ90
<sensor> period required for a 90 % change in sensor output when exposed to a step change in the variable being measured
Note 1 to entry: The response time is signified as τ0.9 in IEC 60751.
[SOURCE: ISO 11139:2018, 3.234, modified — Note 1 to entry added.]
3.22
saturated steam sterilization
validated process which involves the direct contact of saturated steam as the sterilizing agent on product surfaces to achieve the specified requirements for sterility.
Note 1 to entry: This process is typically used to sterilize porous and hard goods (P/HG) products, sometimes known as porous load products.
[SOURCE: ISO 11139:2018/Amd1:2024, 3.368, modified — Note 1 to entry added.]
3.23
simulators
devices which are installed as a permanent fixture in the sterilizer equipped with a temperature sensor which provides data to the automatic controller
3.24
sterilization temperature
minimum temperature on which the evaluation of the sterilization efficacy is based
Note 1 to entry: In saturated steam sterilization processes the sterilization temperature is likely to be a relatively high value, such as 121,1 °C. However, if F0 value accumulation is used to establish the efficacy of a contained product sterilization process the sterilization temperature can be as low as 110 °C.
[SOURCE: ISO 11139:2018, 3.286, modified — Note 1 to entry added.]
3.25
temperature band
<moist heat sterilization> temperature range, the minimum of which is the sterilization temperature
Note 1 to entry: In saturated steam sterilization processes the sterilization temperature band is likely to be a relatively low value, for example 3 °C. However, if F0 value accumulation is used to establish the efficacy of a contained product sterilization process the sterilization temperature band can be as high as, for example 15 °C.
[SOURCE: ISO 11139:2018, 3.293.1, modified — Note 1 to entry added.]
3.26
validation
confirmation process, through the provision of objective evidence, that the requirements for a specific intended use or application have been fulfilled
Note 1 to entry: The objective evidence needed for a validation is the result of a test or other form of determination such as performing alternative calculations or reviewing documents.
Note 2 to entry: The word “validated” is used to designate the corresponding status.
Note 3 to entry: The use conditions for validation can be real or simulated.
Note 4 to entry: One aspect of validation is to provide evidence that the sterilization process is capable of producing an acceptable and repeatable sterility assurance level.
[SOURCE: ISO 11139:2018, 3.313, modified — Note 4 to entry added.]
4.0 General
Unless otherwise specified, conformance with the requirements of this document shall be demonstrated by examination of technical documentation or by visual inspection of the sterilizer.
If specified that conformance shall be established, the reference test method shall be used.
NOTE 1 Test methods of demonstrable equivalence can be used.
NOTE 2 For the purposes of this document the product to which the various sections refer is the sterilizer.
NOTE 3 Sterilizers using saturated steam for sterilizing the surfaces of medical devices are covered by other standards, e.g. EN 285, EN 13060, ANSI/AAMI ST8, ANSI/AAMI ST55, JIS T 7322 and JIS T 7324. Some moist heat / steam sterilizers can be designed to provide both saturated steam sterilization processes and contained fluid sterilization processes. If the sterilizer is designed to provide both saturated steam sterilization processes and contained fluid sterilization processes conformance to whichever is the most relevant standard can be specified in the technical documentation.
4.1 Product definition
4.1.1 When demonstrating that a sterilizer type conforms with this document, sterilizers classified as the same type shall have the same intended use with the same heating medium specification and the same sterilization cycle. See Annex D and particularly D.3 for terminology associated with contained product sterilization. In addition, unless it has been demonstrated that there is no decrease in the performance of an operating cycle, a sterilizer of the same type shall have:
a) the same number of loading or unloading doors;
b) all service connections into the chamber in the same orientation;
c) the same control system with all fixed sensors located in the same position and orientation;
d) the same pre-set programmes of operating cycle(s) including the same cycle parameters.
NOTE 1 A mirror image of the original orientation does not constitute a new type.
NOTE 2 Where a change within the automatic controller system does not affect the sequence of stages of the sterilization cycle, and the parameters limiting the cycle performance, or the safety attributes, such a change does not constitute a new type.
NOTE 3 Some sterilizers for industrial applications are bespoke, one-off designs and so the concept of a type does not apply.
4.1.2 If all other design aspects remain the same, the following variations shall not constitute a new sterilizer type:
a) height of the chamber above the floor;
b) differences in the dimensions of the chamber not greater than ±10 % of the dimensions with congruent sterilizer chamber shapes;
c) prolonging the duration of the plateau period or exposure period of an operating cycle;
NOTE Additional regulatory requirements can apply to prolonging the plateau period or exposure period.
d) prolonging the
1. cooling period in a contained product sterilization process;
2. drying stage in a saturated steam sterilization process;
e) any change of the design or provenance of equipment, providing there is available documented evidence to show there is no decrease in the safety or performance of the sterilizer which can affect conformance with this document.
4.1.1 Equipment development
4.2.1 The design and development process is a critical element in product realization of a sterilizer. To ensure the consistent implementation of the requirements specified in this document, the necessary processes need to be established, implemented and maintained. Processes of particular importance in relation to the design and development of a sterilizer include but are not limited to:
a) risk management;
b) control of documentation, including records;
c) assignment of responsibility;
d) provision of adequate resources, including competent human resources and infrastructure;
e) control of product, including services and equipment, provided by external parties;
f) calibration of instrumentation.
NOTE 1 A formal quality management system such as ISO 9001 or ISO 13485 can be applicable.
NOTE 2 ISO 14971 provides requirements for a risk management system for medical devices.
NOTE 3 ISO 12100 provides requirements for risk management of machinery.
4.1.2 Calibration
4.3.1 All instrumentation fitted to the sterilizer used for monitoring, controlling, indicating or recording shall be calibrated. Instruments used for testing the sterilizer (see Annex H) shall be calibrated. The system(s) for calibration of instrumentation shall provide metrological traceability to a primary standard or national standard with a known level of measurement uncertainty.
NOTE 1 National calibration standards are often mutually recognized and traceable to international standards with recognized fixed-points.
NOTE 2 ISO 10012 specifies requirements for a system of calibration and ISO 13485 includes requirements for the control of monitoring and measuring equipment.
Conformance is demonstrated by inspection of the technical documentation.
4.3.2 Means shall be provided to permit connection of reference instruments for the calibration of instrumentation (see 5.5).
5.0 Equipment design and construction
5.1 Safety and security
5.1.1 General
5.1.1.1 The sterilizer shall conform with IEC 61010-2-040.
NOTE 1 IEC 61010-2-040 provides safety requirements for electrical equipment intended for sterilization, washing, and disinfection of medical materials in the medical, veterinary, pharmaceutical and laboratory fields.
NOTE 2 IEC 61010-2-040 supplements or modifies the corresponding clauses in IEC 61010-1 so as to convert that publication into the IEC standard: Particular requirements for sterilizers and washer-disinfectors used to treat medical materials.
Conformance is demonstrated in accordance with IEC 61010-2-040.
5.1.1.2 Sterilizers shall conform with IEC 61326-1 regarding immunity to electromagnetic interference. The immunity performance criteria selected shall ensure that sterilizer performance is met when exposed to the applicable disturbance phenomena of IEC 61326-1:2020, Table 2.
5.1.1.3 Sterilizers shall incorporate means of protection from unauthorized access that could interfere with its performance or create a hazardous situation. If the sterilizer provides a connection to an IT environment or network, means shall be provided to prevent access or interaction:
a) between that environment or network and the sterilizer that interferes with the sterilizer performance or creates a hazardous situation;
b) between the sterilizer and that environment or network protocol(s) that interferes with the specified performance of the environment or network.
NOTE See IEC 80001-1, ISO/IEC 27001, ISO/IEC 27002, UL 2900-1 and ISO/IEC 21823-1. IEC 80001-1 defines the roles, responsibilities and activities that are necessary for risk management of IT-networks incorporating medical devices to address safety, effectiveness and data and system security. ISO/IEC 27001 specifies the requirements for establishing, implementing, maintaining and continually improving an information security management system and ISO/IEC 27002 gives guidelines for organizational information security standards and information security management practices. UL 2900-1 applies to network-connectable products that need to be evaluated and tested for vulnerabilities, software weaknesses and malware. ISO/IEC 21823-1 provides an overview of interoperability as it applies to Internet of Things systems and a framework for interoperability for such systems.
5.1.2 Over pressure protection devices (OPPD)
5.1.2.1 The chamber, pressurised chamber jacket (if fitted) and steam generator, if integral to the sterilizer, shall be fitted with an over pressure protection device (OPPD, safety valve(s)).
5.1.2.2 The OPPD shall be designed and constructed in accordance with ISO 4126‑1, except that the requirements for minimum bore size of the body seat shall not apply. The bore size shall be sufficiently large to conform with 5.1.2.8.
NOTE Local pressure systems regulations can apply with regard to design details for the OPPD.
5.1.2.3 The OPPD shall be mounted in accordance with ISO 4126‑1:2013+A2:2019, Annex NB.
NOTE Local pressure systems regulations can apply with regard to design details for the OPPD.
5.1.2.4 The OPPD shall be designed to release the pressure within the pressurised section of the sterilizer before the maximum allowable working pressure for that pressurised section is reached.
NOTE Local pressure systems regulations can apply with regard to design details for the OPPD.
5.1.2.5 The OPPD shall be preset and then locked or sealed to prevent adjustment, to prevent the pressure in the pressurised section of the sterilizer from exceeding 110 % of its maximum permissible working pressure.
NOTE See also maximum allowable working pressure.
5.1.2.6 The set pressure of the OPPD shall be not more than the MAWP of the pressurised section of the sterilizer and not less than a value above the maximum permissible working pressure which prevents unnecessary opening of the valve.
Conformance shall be checked by inspection of the OPPD suppliers’ certificate of performance or by establishing performance.
NOTE It is possible to test the pressure at which the OPPD opens. This can be achieved by gradually increasing the pressure in the pressurised section of the sterilizer under test and noting the value at which the OPPD valve opens and checking this value for conformance with the requirements of 5.1.2. This approach can require initiation of a change control procedure within the operational quality system and result in incorrect reseating of the valve resulting in leaks. Consideration can be given to replacement of the OPPD with a newly certified valve according to the instructions for use, during periodic equipment maintenance. A newly certified OPPD valve can be obtained from commercial sources or can be a previously used valve which has been subject to equipment maintenance and recalibrated according to a defined procedure.
5.1.2.7 The OPPD shall close at a pressure not less than the operating pressure; the amount of the blowdown shall be in accordance with ISO 4126‑1:2013+A2:2019, 7.2.1 d).
5.1.2.8 The OPPD shall be of the enclosed type fitted with discharge piping and connected directly to the pressurised section of the sterilizer by means of the shortest possible length of pipe used solely for this purpose, without any intervening cock, filter or valve. The internal diameter of the connecting pipe shall not be smaller than the nominal bore of the OPPD. If the discharge from the OPPD is not visible from the sterilizer, the discharge pipe shall be provided with a small-bore pipe terminating at the sterilizer to give a visible indication of any discharge. The discharge point of the OPPD and the optional small-bore pipe shall be positioned in a location which does not create a hazardous situation
NOTE In some jurisdictions the discharge point would be to an outside location. The small-bore pipe is intended to provide the user with an indication that the OPPD valve has opened.
5.1.3 Over temperature protection devices
5.1.3.1 The requirements for over temperature protection devices specified in IEC 61010-1 and IEC 61010-2-40 shall apply.
NOTE The IEC 61508 series covering those aspects to be considered when electrical/electronic/programmable electronic systems are used to carry out safety functions can also apply.
5.1.3.2 Sterilizers which generate steam within the chamber shall have an over temperature protection device built in.
5.1.4 Door release safety system
5.1.4.1 A door release safety system shall be fitted so that the sterilizer door(s) remain(s) locked at the end of the cooling period of the operating cycle until the load is at a temperature 20 °C below the boiling point of water at the geographic location (altitude) of the site of installation.
NOTE 1 The door release safety system can be the following.
a) A simulator which has an established relationship to the thermal characteristics of a specified load(s) and which has an attached temperature sensor which is connected to the automatic controller.
b) A master timing function within the automatic controller which is set during validation so that the cooling period of the operating cycle is sufficient to ensure the load meets the thermal requirements of 5.1.4.2. This approach relies on a functioning cooling system and use of sensors which ensure the cooling system has operated according to specification during the operating cycle.
c) A combination of a master timing function within the automatic controller and multiple load container temperature probes providing feedback to the automatic controller on load temperature.
NOTE 2 The internal pressures within sealed containers when their temperature is above 80 °C can cause explosive fracture causing a hazardous situation. At standard atmospheric temperature and pressure (STP) the door release safety system can be set to 80 °C. This is decreased as altitude above sea level increases. For plastic containers a setting of 90 °C can be used.
5.1.4.2 The door release safety system shall be a fail-safe.
Conformance shall be established.
5.1.5 Chamber empty protection system.
5.1.5.1 For hot water spray and water immersion contained product sterilization cycles a chamber empty protection system shall be provided to ensure that the water level has lowered sufficiently so that any water flowing out of the chamber when the door(s) is opened does not create a hazardous situation.
NOTE 1 The quantity of water which can flow out of the chamber can be identified by risk assessment.
NOTE 2 This can also be termed a condensate high level warning system.
5.2 Chamber
5.2.1 General
5.2.1.1 The sterilizer design shall allow access to the chamber through either one or two doors.
5.2.1.2 The interior of the chamber shall allow water and steam condensate to drain away from, and the heating medium and cooling medium within the chamber to circulate around, all parts of the load.
NOTE 1 Forced circulation of the heating medium and cooling medium can be used e.g. by use of a rotating blade or pump.
NOTE 2 Examples of the heating medium can be saturated steam, steam-air mixtures or heated water sprays. Examples of the cooling medium can be a cooled water spray.
5.2.1.3 If the chamber is large enough for a person to enter, means shall be provided to protect against entrapment inside the sterilizer chamber. The specifications in IEC 61010-2-040:2020, 7.102 shall apply.
NOTE The means can be lockable by an access device and, if this approach is used, the sterilizers instructions can specify that the operator retain control of the access device while inside the chamber.
5.2.1.4 If the chamber is large enough for a person to enter, a clearly visible warning marking shall be placed on the outside of the equipment instructing the operator to activate the access device before entering the chamber and retaining control of the access device at all times while in the chamber.
5.2.2 Dimensions
5.2.2.1 The internal dimensions of the chamber shall be specified by reference to the principle dimensions at specified positions, measured in millimetres.
a) For cylindrical horizontal or cylindrical vertical chambers:
1. diameter;
2. depth.
b) For rectangular parallelepiped chambers:
1. width;
2. height;
3. depth.
c) For other configurations the chamber shall be specified in analogy to a) or b).
Conformance is demonstrated by measurement using the method described in Annex C.
5.2.2.2 The usable chamber space shall be specified. The following dimensions shall be specified in millimetres and shall represent a theoretical geometric shape which may be inserted or removed through the chamber door into or out of the usable chamber space without obstruction or the need for dismantling of any part of the sterilizer assembly.
a) For cylindrical horizontal or cylindrical vertical usable chamber space:
1. diameter;
2. depth.
NOTE A parallelepiped shaped load carrier can be used in a cylindrical chamber.
b) For rectangular parallelepiped usable chamber space:
1. width;
2. height;
3. depth.
c) For other configurations the chamber shall be specified in analogy to a) or b).
Conformance is demonstrated by measurement using the method described in Annex C.
5.2.3 Design of water dispersion systems within the chamber
Spray jets
If pressurised spray-jets are fitted to provide rapid heating or cooling of the load, a method shall be provided to allow the functioning of each jet to be checked with the chamber door open. The jets should be easily cleaned or replaced.
Dispersion plates
If dispersion plates for gravity water cascade systems are used and are fitted to provide rapid heating and cooling of the load they shall be securely mounted so they can be easily cleaned or replaced. A method shall be provided to allow the functioning of water cascade systems to be checked with the chamber door open.
5.2.4 Doors
General
5.2.4.1.1 The chamber shall be provided with one or two doors for loading and unloading.
5.2.4.1.2 If the chamber is large enough to allow a person or object to be trapped by a moving chamber door, means shall be provided to permit removal before the force and temperature specified in IEC 61010-1:2010+A1:2019, 7.3.4 and 10.1 are exceeded.
NOTE 1 This can be achieved, for example, by automatically reversing the direction of the sterilizer door movement.
NOTE 2 An alarm can operate if the system is activated.
Door classification
5.2.4.2.1 Doors shall be classified by the following types:
a) manually-operated quick action closure;
b) power-operated closure where the door closure is operated automatically by a single action by the operator or semi-automatically, where the door closure is actuated by a continuous action by the operator, e.g. holding a button until the closure action is completed;
c) single or multi-bolt closure.
Door seals
5.2.4.3.1 All interfaces between a door and the chamber shall be fitted with a door seal.
5.2.4.3.2 The sterilizer door seal shall be a replaceable component.
5.2.4.3.3 Connecting compounds shall not be used to permanently attach the door seal to the door or chamber.
5.2.4.3.4 If a lubricating compound is required to allow the door seal to freely move within a restraining channel (e.g. an “o” ring type seal) it shall be established that the lubricant cannot infiltrate the chamber during operating cycles.
5.2.4.3.5 Provision shall be made to permit easy access to the contact surfaces of the door seals for the purposes of cleaning and inspection.
5.2.4.3.6 Provision shall be made in the design of the door to allow replacement of the door-seal without the need to dismantle the door assembly.
NOTE Personal protective equipment can be needed if adjacent surfaces are hot.
Doors and their controls
General
5.2.4.4.1.1 The following shall apply to all door closure types.
a) After closing the sterilizer door, it shall be possible to reopen it before it is locked and an operating cycle has been started.
NOTE Other than where this conflicts with the requirements for double door sterilizers.
b) The door shall be locked before an operating cycle is initiated.
c) There shall be a visual indication when the door(s) is/are closed and locked.
d) Door interlock switches shall be positively operated.
e) Pressurising fluids shall not enter the chamber until the door is closed and locked.
f) It shall not be possible to open the door when an operating cycle is in progress.
g) It shall not be possible to open the door until the chamber has been vented and the chamber pressure is within +/- 20 kPa of atmospheric pressure.
Conformity shall be established following a procedure indicated by the technical documentation or the instructions for use.
5.2.4.4.1.2 The doors shall be capable of being unlocked and opened only after successful completion of an operating cycle and cycle complete indicated.
5.2.4.4.1.3 If an operating cycle has not successfully completed the door(s) shall only be capable of being unlocked and opened by means of a door control access device.
5.2.4.4.1.4 The door(s) shall not be capable of being opened if it will create a hazardous situation.
NOTE 1 Examples of a hazardous situation are residual pressure inside the chamber or the load above 80 °C (see Annex K).
NOTE 2 The instructions accompanying the sterilizer provides guidance on how to restore the sterilizer to a safe state if a hazardous situation has been identified.
5.2.4.4.1.5 If, during an operating cycle, the sterilizer becomes isolated from any of the services powering the door movement, the position of the door shall remain unchanged.
5.2.4.4.1.6 If the services powering the door fail whilst the door is opening or closing this failure shall not create a hazardous situation. The restoration of services powering the door after a failure shall not create a hazardous situation.
NOTE An example of a hazardous situation is if after a service interruption the door continued to close once the services were restored.
5.2.4.4.1.7 If the sterilizer becomes isolated from any of the services powering the door mechanism this occurrence shall not allow a hazardous situation to occur (see 5.2.4.4.1.6).
5.2.4.4.1.8 If, when opening, the door or its mechanism protrudes into the plant room or similar working area, that section of the door and its mechanism shall be so designed and constructed so as not to create a hazardous situation. If this cannot be achieved, guard rails and similar safeguards shall be used.
NOTE See IEC 61010-2-40.
5.2.4.4.1.9 All door interlock systems shall be fail-safe and shall incorporate two or more independent interlocks such that in the event of failure of any one service or any one interlock, at least one of the interlocks will continue to function.
Conformance is checked:
a) by inspection of the interlocks;
b) after disabling each service and each interlock in turn demonstrating the door(s) remain locked.
Manually operated doors
5.2.4.4.2.1 If the door is locked by means of a screwed spindle, it shall be fitted with a heat-insulated handwheel or handles.
5.2.4.4.2.2 Instructions shall be displayed on the facia panel adjacent to the door or the operators control panel describing the actions required to close and lock and unlock and open the door.
5.2.4.4.2.3 The door mechanism shall be such that the force to be applied by an operator in order to either lock or unlock the door does not exceed 250 N.
Specific requirements for double-ended sterilizers
5.2.4.4.3.1 If an operating cycle is started by a user interface mounted on or near to the sterilizer this shall be mounted at the loading end of the sterilizer.
NOTE In industrial settings control of the sterilizer can take place remotely from the location of the sterilizer in a control room (e.g. a SCADA control system).
5.2.4.4.3.2 Except for equipment maintenance and test purposes it shall not be possible for more than one sterilizer door to be open at the same time.
5.2.4.4.3.3 Opening of both sterilizer doors shall be controlled by a door control access device.
5.2.4.4.3.4 Prior to the commencement of a sterilization cycle the loading door shall be unlocked and the unloading door locked.
5.2.4.4.3.5 When a sterilization cycle has started it shall not be possible to open either door and the unloading door until cycle complete is indicated.
5.2.4.4.3.6 Upon successful completion of a sterilization cycle when cycle complete has been indicated the unloading door shall be unlocked and the loading door shall remain locked in a double-ended sterilizer.
5.2.4.4.3.7 If, at the end of a sterilization cycle, cycle complete is not indicated then both the unloading door and loading door shall remain locked until a door control access device is used.
5.2.4.4.3.8 Use of the door control access device shall either
a) unlock the loading door whilst the unloading door remains locked; or
b) unlock the unloading door whilst the loading door remains locked.
NOTE If a cycle complete is not indicated at the end of a sterilization cycle then the load can be regarded as non-conforming. The direction in which the load is removed from the sterilizer depends on the application and can require that the load be removed from the loading door or from the unloading door after the door control access device has been used.
5.2.4.4.3.9 The action which use of the door control access device provides (see 5.2.4.4.3.8) shall be selectable by use of a door control access device within the automatic controller.
NOTE The action which the door control access device provides can be set during works testing or installation qualification according to users’ requirements.
5.2.5 Chamber integrity
5.2.5.1 Means shall be provided to conduct a leak test(s) capable of detecting a leak if a leak of fluids, including air leakage, into or from the chamber or connected relevant pipework can
a) create a hazardous situation;
b) affect the intended function of the equipment or overall performance of the equipment or process.
5.2.6 Pressure vessels
5.2.6.1 The chamber and associated pressure vessels shall be designed to withstand a specified maximum allowable working pressure.
Conformance shall be demonstrated by inspection of the technical documentation.
NOTE 1 The technical documentation can contain both calculations and engineering drawings illustrating the manner by which design parameters have been derived.
NOTE 2 Local and regional regulations and standards can apply in certain jurisdictions e.g. EN 13445-1, EN 13445-2, EN 13445-3, EN 13445-4, EN 13445-5, and EN 13445-8, and also other national standards.
5.2.6.2 The maximum allowable working pressure shall allow one or a number of operating cycles to be safely carried out including those which include not only a specified saturated steam pressure but also include a balancing non-condensable gas overpressure.
NOTE 1 A balancing non-condensable gas overpressure can be used to prevent container deformation or bursting or protect the integrity of the container closure system. In such circumstances the total pressure in the system will be the sum of the steam pressure plus the non-condensable gas overpressure.
NOTE 2 In a health care setting a number of operating cycles can be implemented in the automatic controller using sterilization temperatures in the range 121 °C to 137 °C (ca 2 to 3,5 BarA in saturated steam). In an industrial setting user configured operating cycles can be implemented specific to load configuration(s) which will be sterilized within a specified sterilization temperature band and pressure.
5.2.6.3 During works testing pressure vessels shall be hydraulically tested for integrity and compliance with relevant pressure vessel regulations.
NOTE Local and regional standards can apply, e.g. EN 13445-1, EN 13445-5 and EN 13445-8, and also other national standards.
5.2.6.4 The design life of the pressure vessel(s) shall be specified in the technical documentation.
NOTE Typically pressure vessels covered by this standard can be designed to withstand at least a number of operating cycles calculated by dividing 25 000 by the minimum operating cycle time, in hours.
5.2.7 Uniformity of conditions
5.2.7.1 The performance requirements and uniformity of conditions for contained fluid sterilizers shall be determined by the product to be sterilized, the size of the useable chamber space and the parameters used during each stage of the sterilization cycle.
NOTE 1 The supply of services can influence the specified performance requirements.
NOTE 2 In a health care setting a number of operating cycles can be implemented in the automatic controller using sterilization temperatures in the range 121 °C to 137 °C (ca 2 to 3,5 BarA in saturated steam). In an industrial setting user configured operating cycles can be implemented specific to load configuration(s) which will be sterilized within a specified sterilization temperature band and pressure.
5.2.7.2 The conditions within the usable chamber space shall be maintained within the tolerances specified for the sterilization cycle (empty chamber test).
Conformance shall be established by comparing parameters or specified outcomes to results of measurements of process variables and cycle variables at representative position(s) throughout the usable chamber space with the chamber empty according to the method described in F.2.
5.2.7.3 The conditions within specified test loads shall be maintained within the tolerances specified for the sterilization cycle.
Conformance shall be established by comparing parameters or specified outcomes to results of measurements of process and cycle variables at representative positions throughout the specified test load.
NOTE 1 In an industrial setting the user can specify a load of simulated product. In a health care facility the sterilizer can be designed to process multiple load configurations. The reference loads described in Annex F can be used to establish the basic performance of the sterilizer when processing a load of low thermal capacity and when processing a load of high thermal capacity.
NOTE 2 Results from biological indicators or chemical indicators can be used to supplement the measurements that can be made.
NOTE 3 Some regulatory authorities require the use of appropriate biological indicators or chemical indicators e.g. United States Pharmacopoeia, European Pharmacopoeia.
5.2.8 Ancillary equipment and components
Load carrier and load handling equipment
5.2.8.1.1 A load carrier shall be provided to allow insertion and removal of the load from the chamber.
NOTE 1 Particular attention can be given to the design of load carriers for small volume containers (i.e. less than 100 ml) to ensure conformance.
NOTE 2 A load carrier is the framework on which load items are mounted. Load handling equipment is the means by which the load carrier is inserted into the chamber such as a manually operated trolley or an automatic load transportation system.
5.2.8.1.2 The load carrier shall allow one or more specified loading configurations to be used.
5.2.8.1.3 The load carrier shall maintain the load in its intended position within the usable chamber space for the duration of the operating cycle.
NOTE Some sterilizers can have a means by which the load is agitated during an operating cycle. This can be by rotation of the load carrier or shaking. If such a process is employed then the load carrier can be designed to ensure containers of the load remain stable and in position during rotation or shaking.
5.2.8.1.4 The load carrier shall not prevent the attainment of the specified process variables and cycle variables and their associated process parameters and cycle parameters.
5.2.8.1.5 The load carrier shall allow the drainage of water and steam condensate from the load and the penetration of the heating medium into all parts of the load during an operating cycle.
5.2.8.1.6 For manually loaded sterilizers, load handling equipment shall be provided.
5.2.8.1.7 For manually loaded sterilizers, the force required by the operator when using the load handling equipment to insert or remove the whole or part of the load from the chamber shall not exceed 250 N.
NOTE The load handling equipment can be a powered mechanical device.
5.2.8.1.8 For manually loaded sterilizers, any load carrier mounted on its handling equipment, e.g. a trolley, shall remain stable when it is supporting its maximum design load and a force of 250 N is applied horizontally in any direction to the highest point of the load carrier (see 5.2.8.1.1, NOTE 2).
The load handling equipment should minimize the hazard of breakages and should safeguard personnel when loads are being moved.
5.2.8.1.9 For automatically loaded sterilizers (e.g. a conveyor system), the load handling equipment shall be designed to avoid hazardous situations arising during operation.
5.2.8.1.10 The safety of the design of the load handling equipment shall be established by risk assessment.
NOTE Local and regional standards and regulations can apply to automated conveyor systems.
Filters
5.2.8.2.1 If a filter is fitted to the sterilizer and is intended to retain microbial contamination at a specified stage of the operating cycle, it shall:
a) conform with ISO 13408-2:2018, Clause 5 and in addition the nominal penetrating particle size shall be 0,3 microns or smaller;
b) be microbially retentive, as specified by the filter manufacturer;
c) be suitable for the application;
d) be readily accessible for replacement;
NOTE Mounting the filter so that there is a clear space of not less than 100 mm surrounding the external faces of the filter can allow ready access.
e) be equipped with means to prevent unintended fluid flow from the chamber into the filter;
f) be so installed that it is not subjected in normal use to more than 80 % of the manufacturer’s stated maximum differential operating pressure;
g) if required, be capable of being subjected to an in-situ decontamination process e.g. a “steam in place” decontamination process;
h) be capable of being integrity tested in-situ.
5.2.8.2.2 If a filter is fitted to the sterilizer but is not intended to retain microbial contamination, it shall:
a) conform with ISO 13408-2;
b) be suitable for the application;
c) be readily accessible for replacement;
NOTE Mounting the filter so that there is a clear space of not less than 100 mm surrounding the external faces of the filter can allow ready access.
d) be equipped with means to prevent unintended fluid flow from the chamber into the filter;
e) be so installed that it is not subjected in normal use to more than 80 % of the manufacturer’s stated maximum differential operating pressure.
5.2.8.2.3 If the filter is required to allow outward flow from the sterilizer, e.g. is required to be subjected to the chamber heating medium and thus is liable to become wet, the requirements in 5.2.8.2.1 shall not apply.
5.2.8.2.4 If the filter is required to allow outward flow from the sterilizer, the filter shall
a) be designed to allow bi-directional flow;
b) be constructed of materials which retain their properties if they become wet and hot;
c) function at pressures and temperatures not less than 10 % above those which are used in the sterilizing stage of the operating cycle.
Conformance is demonstrated by inspection of the technical documentation.
Air filters should be constructed from materials resistant to corrosion and biodegradation. The filter material should be supported in a manner which restricts its distortion and movement during use in order to minimize damage to the filter material.
Pipes and valves
5.2.8.3.1 Materials in contact with steam shall conform with 5.3.
5.2.8.3.2 Pipe joints and fittings shall be visibly pressure tight and if applicable, vacuum tight.
5.2.8.3.3.1 Except where this will interfere with the function of the sterilizer the pipework carrying a fluid greater than 60 °C shall be thermally insulated. Cold water pipework shall also be thermally insulated.
5.2.8.3.3.2 If the sterilizer is enclosed within a cabinet then 5.2.8.3.3.1 shall not apply unless a risk assessment identifies a hazardous situation to an operator as a result of removing the cabinet or gaining access within e.g. removal of the cabinet for equipment maintenance purposes.
5.2.8.3.4 Pipework to an enclosed discharge shall have, wherever practicable, a continuous fall to the discharge point. If this cannot be achieved, the lowest part of any falling section shall be fitted with a water and steam condensate drain.
5.2.8.3.5 No valve connected to the chamber shall be fitted where the system temperatures and pressures can exceed 80 % of the maximum design tolerance stated by the manufacturer of the valve.
5.2.8.3.6 Data shall be retained to show that each type of valve used is capable of operating correctly for a specified minimum number of specified operating cycles. These data shall be available to the purchaser, if requested, and shall inform an equipment maintenance schedule.
5.2.8.3.7 Means shall be provided to prevent the ingress of particulates of a size or quantity which could affect the performance of the sterilizer.
NOTE Strainers or filters of a relevant pore size can be used.
5.3 Materials
5.3.1 The sterilizer and ancillary equipment (e.g. the load carrier) shall be made of materials which, in normal use, will not react with, and resist chemical attack from, the heating medium (e.g. saturated steam, steam-air/gas mixtures, heated water sprays), cooling medium, carrier fluids or other fluids (e.g. condensate) coming into contact with the material in a manner and to an extent that can lead to deterioration that can:
a) affect the operation of the sterilization cycle;
b) have a detrimental effect on the materials of construction;
c) release a substance known to be toxic in such quantity that would create a health or environmental hazard;
d) create a hazardous situation;
e) release substances which could have an adverse effect on the load, heating medium, cooling medium carrier fluids or other fluids present in the sterilizer.
NOTE Because of the different types of sterilizers and the large number of uses, it is not possible to specify detailed requirements for materials specific to an application. EN 13445-2 specifies materials which can be used to manufacture pressure vessels e.g. CrNiMo steel. Other useful reference standards include ASME B31.3, ASME BPE and ASME BPVC.
The load carrier should be constructed from durable, corrosion-resistant materials.
Conformity is checked by inspection, and by examination of data accumulated by the manufacturer of the sterilizer or supplier of materials during failure-mode and effects analysis and during tests, to demonstrate that the materials used and specified are compatible with any heating medium, cooling medium or carrier fluids with which they make contact.
5.3.1 Interlocks
Sterilizers shall be equipped with an interlock so that, under conditions of normal operation, the pressure in the chamber cannot be increased or decreased and heating medium and other fluids cannot enter or escape from the chamber when the door(s) is unlocked or unsealed.
Conformance is demonstrated by inspection of the technical documentation.
NOTE For interlocks for sterilizer doors, see 5.2.4.
5.3.2 Test connections
5.5.1 The sterilizer shall be equipped with at least one test connection flange which shall be welded in place and capped off and sealed during normal operation.
NOTE 1 A suitably sized ball valve can be fitted proximal to the chamber to allow a secondary means of sealing when the test connection is not in use.
NOTE 2 means for mounting sensors and associated cabling internal to the chamber can be provided e.g. suitable brackets permanently fixed to the internal chamber wall.
5.5.2 The test connection(s) shall be of either a tri-clamp connection system or a pipe stub with an external pipe thread according to ISO 228-1:2000 designation G 1/2 A.
NOTE The ASME Bioprocessing Equipment (BPE) guidance provides suitable designs for tri-clamp systems. EN 285 provides suitable designs for test connections using a pipe stub.
5.5.3 The number and dimensions of hygienic design test connection(s) and how test equipment can be introduced into the sterilizer chamber shall be specified in the technical documentation.
NOTE 1 The test connection can be 25 mm or 37,5 mm in diameter.
NOTE 2 Keeping the number of test connections to a minimum reduces the risk of leakage.
5.5.4 An adapter(s) shall be provided as an accessory item to allow the introduction of measuring sensors into the chamber.
5.5.5 The test connection shall be designed such that a number of measuring sensors can be introduced into the chamber and then sealed in place without affecting the integrity of the chamber.
NOTE 1 Test connections can achieve a pressure tight seal by compression or tri-clamp fittings.
NOTE 2 Once sensors are fitted the integrity of the chamber can be checked by conducting a chamber integrity test before further tests are conducted.
5.5.6 Test connection(s) shall be designed in such a way that all areas of the chamber can be reached in a suitable manner with suitable measurement techniques.
5.5.7 Test connections shall be at points of easy access, but not in pipes for media/fluid transport (e.g. steam, air, water).
5.5.8 The test connection shall provide access into the sterilizer chamber providing it causes no adverse effect on the measurement of the conditions in the sterilizer chamber.
5.5.9 The test connections shall be sealed and provided with means to prevent physical or chemical damage.
5.5.10 If a test connection can be opened and closed without the use of an access device, means shall be provided to prevent opening if conditions inside the equipment could cause a hazardous situation
NOTE Means can include interlocks, fitting an interlocked cover over the test connection or providing a protective barrier to avoid creation of a hazardous situation (see 5.5.1 NOTE 1).
5.5.11 Test tee(s) and valve cock(s) with sealing plugs shall be fitted to permit connection of reference test instruments for the calibration of all pressure instruments connected to the chamber or pressurised sections of the sterilizer.
5.3.3 Vibration
5.6.1 Vibrations from sterilizers shall be reduced by design, selection of components and devices limiting vibrations, particularly at source. If vibrations can cause a loss of stability of the sterilizer, means shall be provided for suitable fixation.
NOTE 1 Guidance to reduce vibration at source is provided in ISO 12100:2010, 6.2.2.2, 6.2.3; 6.2.6 and 6.3.4.3.
NOTE 2 Vibration from other sources applicable to the intended use of the sterilizer can also be considered.
5.3.4 User interfaces
5.7.1 The control used to start the operating cycle shall be located adjacent to the loading door or in a remote operating facility.
5.7.2 If used, a remote operating facility shall provide at least an equal level of monitoring and safety as operation from the loading side of the sterilizer. This shall include a means by which a door cannot be closed until an operator(s) loading the chamber has indicated to the remote operating facility that they are no longer in a hazardous situation. The level of safety provided by the means shall be assessed by risk assessment.
NOTE This can be achieved by the use of an access device in the personal possession of the operator(s) loading the chamber. See also 5.2.4.4 on door controls.
5.7.3 An emergency stop system shall be provided in a readily accessible point near the sterilizer. If activated this shall only be reset by use of an access device.
NOTE More than one emergency stop system can be provided. See IEC 61010-2-040:2020, 7.110.
5.7.4 Mechanical pressure gauges showing the chamber and pressurised sections of the sterilizer pressures shall be fitted close to the loading door for single door sterilizers and near both the loading and unloading doors for double-ended sterilizers.
5.7.5 The user interface shall provide the following:
a) a means by which individuals who interact with the automatic controller can be identified;
NOTE 1 This can be by means of an access device such as entry of a personalised keyboard password or use of a personal radio frequency identification device (RFID).
b) a means of entering an access code to operate the sterilizer;
c) an indication of individuals capabilities to select specific cycles once identified (see a));
d) an on/off switch for the sterilizer;
e) a means for selection of approved cycles
f) once selected, an indication of the operating cycle;
g) an operating cycle counter;
h) an indication that the door is locked;
i) a display of the pressure inside the sterilizer chamber;
j) a display of the temperature inside the sterilizer chamber;
k) if used, a display of the temperature within the product to be sterilized or a reference container;
l) an indication of each process stage as the operating cycle progresses;
m) a display of the sterilizing (holding) time;
n) for time controlled operating cycles, a display of the time remaining;
o) a display of “cycle complete” (program end) if the operating cycle completes satisfactorily;
p) an alarm to notify cycle complete has not been satisfied;
q) an indication of a fault and the nature of the fault if one arises;
NOTE 2 The nature of the fault can be in the form of a code which is explained in the instructions for use or on a label attached to the facia panelling.
r) the accumulated F0 value, if used, from the specified reference point.
5.7.6 If a fault is indicated, or on completion of an operating cycle for test or equipment maintenance purposes, it shall not be possible to open a door without the use of an access device.
5.7.7 Double-ended sterilizers shall be provided with the indicating devices specified in 5.7.5 at both ends of the sterilizer (see also 5.2.4.4).
5.7.7.1 Means shall be provided for the user to terminate the sterilization cycle or the operating cycle without causing a hazardous situation. This shall only be possible after use of an access device.
5.7.7.2 If a fault results in aborting or terminating an operating cycle in progress, the visual indication of the fault shall continue until the user completes a specified action e.g. use of an access device, to clear the indication of the fault.
5.7.7.3 If an operating cycle is interrupted, opening of the sterilizer door shall require the use of an access device.
5.7.7.4 If the operating cycle is manually aborted, or a fault results in the operating cycle prematurely terminating it shall not be possible to open the door(s) of the sterilizer if this will cause a hazardous situation e.g. the load is above 80 °C, the chamber has coolant or process water present above a specified level (see 5.1.4).
5.7.7.5 Means shall be provided to permit operation of the sterilizer for equipment maintenance, test purposes and in cases of emergency, without causing a hazardous situation.
5.7.7.6 The activation of any equipment maintenance mode shall be clearly indicated in order to avoid safety features being inactivated during normal operations.
5.7.7.7 Indicating, measuring and recording instruments shall be identified as to their function.
5.7.7.8 The displays from instruments and indicating devices shall be located where they can be viewed readily by the user under normal operation of the sterilizer.
5.7.7.9 Instruments and gauges shall be readable by normal or corrected vision from a distance of 1 m and with a minimum illumination of (215 ± 15) lx.
5.7.7.10 If an instrument on the sterilizer is adjustable, adjustment shall require the use of an access device.
5.7.7.11 When fitted, acoustic signals not associated with a hazardous situation shall be time-limited to 30 s or it shall be possible to interrupt them.
6.0 Indicating, monitoring, controlling and recording
6.1 General
6.1.1 The process parameters and cycle parameters for controlling, monitoring, recording and indicating the operating cycle(s) shall be established and incorporated into pre-set program(s) of the sterilizer.
NOTE 1 For moist heat sterilization processes the process variables are temperature and time of exposure in the presence of moisture. Moisture is provided by the contents of the contained product. Temperature is achieved within the contained product by use of a heating medium within the chamber. Satisfactory exposure time is achieved by use of a validated plateau period, exposure period or integrated lethality factor, F0 value pre-programmed in the automatic controller. Validation of moist heat sterilization processes is considered in ISO 17665.
NOTE 2 For contained fluid sterilization processes the cycle variables which can be considered are the temperature, pressure and time of exposure along with such variables as chamber content circulation system speed for steam/air mixture sterilization processes or water flow rate for heated water spray sterilization processes.
6.1.2 All instruments and control systems shall be designed, positioned or protected so that their performance is maintained when at the installed geographical location and when the sterilizer is in operation.
6.1.1 Automatic control
6.2.1 The sterilizer shall operate with pre-set programs permanently stored in the automatic controller.
6.2.2 Means shall be provided to ensure that a failure in a control function does not lead to a failure in recording of process parameters such that an ineffective process appears effective or leads to a hazardous situation. This shall be achieved either by the use of independent systems for control and recording, or by a cross-check between control and recording that identifies any discrepancies and indicates a fault.
NOTE 1 Examples of the interrelationship between control, monitoring and recording are illustrated in Annex B.
6.2.3.1 Automatic controllers shall incorporate at least two timing systems, independent of each other and such that the timer used to monitor the sterilization stage is verified by the secondary timer. Timers shall be provided for control, monitoring, and recording of the operating cycle stages. Time periods shall have a measurement error not exceeding 1 s.
NOTE 1 Timers are typically part of automatic controllers (external) recorders and printers.
NOTE 2 Examples of the interrelationship between control and recording are illustrated in Annex B.
6.2.4 The automatic controller shall not cause a hazardous situation, if:
a) the values of cycle parameters are outside the specified limits;
b) a power failure occurs;
c) a failure of other services occurs.
6.2.5 Software for monitoring and control shall be verified and validated. The methods used in the verification and validation processes shall be selected based on the intended purpose of the software.
The methods shall be justified and specified.
NOTE See, for example, the IEC 61508 series, IEC 62304 and IEC 62061. The IEC 61508 series applies to safety-related systems when one or more of such systems incorporate electrical or electronic or programmable electronic devices. IEC 62304 defines the life cycle requirements for medical device software. IEC 62061 specifies and makes recommendations for the design, integration and validation of safety-related electrical, electronic and programmable electronic control systems for machines.
6.2.6 The automatic controller shall be protected against any fault condition which can occur in components or equipment, directly or indirectly connected to the controller such as short circuits.
NOTE See IEC 60204–1 or IEC 60335-1. Verification can be achieved by assessing conformance with IEC 60204–1 or IEC 60335-1. IEC 60204–1 applies to non-portable electrical, electronic and programmable electronic equipment and systems to machines. IEC 60335-1 deals with the safety of electrical appliances for household and similar purposes including appliances not intended for normal household use but which nevertheless can be a source of danger to the public, such as appliances intended to be used by laymen in shops.
6.2.7 The automatic controller shall have means to detect whether any control sensors are in a fault condition, such as a broken sensor, and ensure that no hazardous situation occurs as a result.
NOTE The automatic controller can fail to safety either by electronic or mechanical means.
6.2.8 The automatic controller shall be located such that the maximum values of temperature, humidity and any limiting ambient pressure values specified for the automatic controller are not exceeded.
NOTE 1 Depending on the installation’s geographical location ambient conditions can cover a wide range of temperature and humidity, particularly when the sterilizer is in operation e.g. 10 °C to 50 °C and 10 % to 95 % RH.
NOTE 2 Instruments and control systems can be mounted in air-conditioned cabinets to maintain them within specified environmental conditions and design tolerances.
6.2.9 Means shall be provided so that if a failure of the automatic controller occurs, the door can be opened using an access device without causing a hazardous situation. It shall be verified that the access device is available or in place and is functional.
NOTE The access device can be a mechanical system which is independent of the automatic controller.
6.2.10 The automatic controller shall have connections provided to enable the instruments and process controls to be independently verified during an operating cycle.
6.2.11 Any control parameter which is pre-set but adjustable shall require the use of an access device for its adjustment.
6.1.2 Control and monitoring system
6.3.1 The automatic controller, monitoring system and recorder shall be capable of measuring at least the following operating cycle parameters.
a) For indication:
1. temperature in the chamber;
2. absolute pressure in the chamber, for double ended sterilizers this shall be provided at each end;
3. absolute pressure in a pressurised jacket;
4. if fitted, the temperature in a load item or reference container and, if used, the accumulating F0 value;
5. the output from any sensor systems required to ensure the operating cycle is functioning according to its specification.
NOTE 1 This can be a simple indication such as a flashing green light.
NOTE 2 For contained fluid sterilization processes, examples can include the rotation speed of the circulation system used to ensure homogeneity of the chamber environment during a steam-air mixture contained fluid sterilization process and the flow rate of the circulating water in a superheated water spray contained fluid sterilization process.
b) For control:
1. temperature in the chamber;
2. if fitted, temperature in the load item;
3. absolute pressure in the chamber for control;
4. if fitted, temperature in the door release safety system or other simulator system;
5. if fitted, temperature in the load item for the calculation of F0 value and the accumulating F0 value;
6. the output from any sensor systems required to ensure the operating cycle is functioning according to its specification.
NOTE 3 For contained fluid sterilization processes, examples can include the rotation speed of the circulation system used to ensure homogeneity of the chamber environment during a steam-air mixture contained fluid sterilization process and the flow rate of the circulating water in a superheated water spray contained fluid sterilization process.
c) For recording:
1. temperature in the chamber;
2. absolute pressure in the chamber for recording;
3. if fitted, the temperature in the load item and if used the calculated F0 value and the accumulating F0 value;
4. if fitted temperature in the door control safety system or other simulator system;
5. the output from any sensor systems required to ensure the operating cycle is functioning according to its specification.
NOTE 4 For contained fluid sterilization processes, examples can include the rotation speed of the circulation system used to ensure homogeneity of the chamber environment during a steam-air mixture contained fluid sterilization process and the flow rate of the circulating water in a superheated water spray contained fluid sterilization process.
6.3.1.1 The automatic controller and monitoring and recording system shall have separate measuring chains for the measurement of control data and independent data for the monitoring and recording system (see Annex B).
6.3.1.2 The automatic controller and monitoring and recording system measuring chains for the measurement of control data and independent data for the monitoring system shall either be wired or make use of wireless data transmission.
6.3.1.3 It shall be established that under normal operation corruption of data cannot occur.
NOTE Wireless data transmission can be affected by, for example, extraneous electromagnetic sources of energy or other data transmission devices. The IEC 62657 series of standards address the challenges encountered in managing multiple wireless systems.
6.3.1.4 Independent measuring chains for controlling and monitoring and recording shall be used for specified cycle variables and process variables.
6.3.1.5 Separate analogue to digital converters shall be used for the control data and independent data.
NOTE 1 Measurement systems providing a higher level of redundancy can be used.
NOTE 2 Risk analysis identifies which cycle variables or process variables require redundant supervision.
6.3.1.6 The automatic controller and monitoring system shall check during an operating cycle whether there is less than 0,5 °C difference between corresponding measuring chains. If the difference is greater than 0,5 °C a fault shall be indicated.
NOTE See EN 285.
6.3.2 The automatic controller and monitoring and recording system shall have software code that processes the control data and the recorded data independently of each other.
6.3.3 Data from the process control measuring chain shall be provided to the automatic controller.
6.3.4 The data from an independent measuring chain shall be provided as a one-way flow to the recording function.
NOTE This does not exclude the transfer of informative data between the control function and failure detection, and data retention, via a combined system for data transfer.
6.3.5 The automatic controller and monitoring system shall include means for failure detection. This shall receive both processed control data and independent data and shall indicate a failure and provide an alarm if the control data and independent data differ from specified conditions.
6.3.6 The independent data and the control data shall be stored in a data retention module, along with notification of failures. These data shall be transferred to a recorder that may be integrated into the control and monitoring system, built into the sterilizer, or as an external device(s).
NOTE The external device can be a specific local device, or a remote data storage device.
6.3.7 A printer may be provided as an option.
6.1.3 Failure
6.1.4 General
6.4.1.1 Failure of items critical to process or safety, including the operating equipment and services, shall be detected by the automatic controller of the equipment.
NOTE 1 A failure can require different types of indications depending upon its potential effects and urgency, such as audible/visual alarms, warnings, error indications, messages, displays, as well as subsequent automated responses of equipment or correction by the operator.
NOTE 2 The consequences of a failure can depend on the current operation mode of the equipment. Different levels for alarms and indications depending on the related criticality can be provided.
6.4.1.2 Such failure of items critical to process or safety detected by the monitoring system of the equipment shall be indicated and explained in the instructions for use regarding the activation conditions, the intended or potential consequences and the required correction.
Conformance is demonstrated by inspection of the technical documentation and the instructions for use.
6.1.5 Fault
6.4.2.1 If a failure addressed by 6.4.1.1 causes one or more of the process or cycle parameters to be outside specified tolerances during an operating cycle, or if an operating cycle is interrupted by the operator, a fault shall be indicated and shall cause an audible or visual alarm.
Conformance is demonstrated by inspection of the technical documentation.
6.4.2.2 If a fault is indicated, the current operating cycle stage shall be stopped and identified by the record.
Conformance is demonstrated by inspection of the technical documentation.
6.4.2.3 Any visualization of a fault indication shall be distinguishable from the indication of a satisfactory operating cycle.
Conformance is demonstrated by inspection.
6.4.2.4 After a fault has been indicated, the automatic controller shall permit automatic progress to a cooling stage if the heating medium has been admitted to the chamber, followed by operating stages for recovery of the system which, when completed, allows the loading door to be opened without creating a hazardous situation.
Conformance is demonstrated by inspection of the technical documentation.
6.4.2.5 After completion of the recovery operating stages "cycle complete" shall not be indicated, access to the sterilizer load shall require the use of an access device.
NOTE Additional requirements and guidance regarding faults and safety can be found in IEC 61010-2-040.
Conformance is demonstrated by inspection.
6.4.2.6 Failure of any sensor connected to the automatic controller shall cause a fault to be indicated.
6.4.2.7 Any failure of the electricity supply during an operating cycle that is sufficient to interrupt or affect the control of the operating cycle by the automatic controller shall be indicated on restoration of the electrical power supply by the following:
a) an immediate visual indication on the control panel that a fault has occurred;
b) an auditory alarm, which can preferably be muted;
c) a visual indication of the stage of the operating cycle at which the fault occurred.
6.4.2.8 A fault shall be indicated on the occurrence of either:
a) a failure of any service, other than the electricity supply (e.g. water, air, steam or the drainage system) essential to the completion of the operating cycle; or
b) a failure detected by a monitoring device, e.g. a stage timer or a water level alarm.
6.4.2.9 After a fault has been indicated, the automatic controller shall either:
a) permit completion of all stages of the operating cycle at the completion of which there shall be no indication of “cycle complete”; or
b) prevent the automatic progress of the operating cycle but allow manual control of the cycle.
6.4.2.10 A visual display of a fault shall continue at least until the release of the door-locking mechanism by the use of manual control (see 13.8).
6.1.6 Power failure
In the event of a power failure which causes a fault, 6.4.2 shall apply after restoration of the power.
Conformance is demonstrated in accordance with 6.4.2.
6.1.7 Other failures
6.4.4.1 If a failure of the operating equipment, the current operating cycle, or any service does not create a fault, its indication shall be distinguishable from a fault indication.
Conformance is demonstrated by inspection of the technical documentation.
6.4.4.2 If a failure can create a fault at a later stage of an operating cycle, or after initiation of another operating cycle, a respective warning shall be displayed.
Conformance is demonstrated by inspection of the technical documentation.
6.4.4.3 If a failure can create a hazardous situation, the controller, in combination with other safety systems, shall automatically initiate action to prevent a hazardous situation. The failure shall be indicated by an audible and visible alarm. The alarm indication shall allow the operator to identify the failure and shall provide a directive by text or by reference to an instruction manual for correction. The failure indication shall be recorded in order to allow retrospective identification and analysis.
Conformance is demonstrated by inspection of the technical documentation.
6.4.4.4 Any other failure may be displayed as a message as appropriate.
6.2 Instrumentation
6.5.1 The sterilizer shall be provided with instruments to allow measurement and control of the cycle variables temperature, pressure, time, and if fitted accumulated Fo value and any other sensor required to ensure that the operating cycle is carried out according to its specification e.g. chamber circulation system speed, water spray pressure/flow rate.
Conformance is demonstrated by inspection of the technical documentation.
6.5.2 Instruments shall cover the scale range applicable to the operating cycle(s) programmed into the automatic controller.
6.5.2.1 Instruments shall have specified accuracy or maximal permissible errors sufficient for the automatic control to respond to deviations from the tolerances of the cycle parameters.
6.5.2.2 The data sampling rate and the response time of sensors and measuring chains shall be appropriate to represent the sterilization process.
6.5.2.3 The following instrumentation characteristics shall permit control of the sterilization process within the specified cycle or process parameters:
a) data sampling rate;
b) control system response time;
c) hysteresis;
d) maximal permissible errors;
e) error caused by changes in ambient conditions.
Conformance is demonstrated by inspection of the specifications of the instrumentation and control system with the specified cycle or process parameters and the rate at which these parameters change during an operating cycle.
6.5.2.4 The process variables for a moist heat sterilization process are time at an appropriate temperature in the presence of moisture. These are created from the aqueous liquid in the contained product. Time can be specified as an exposure period, a holding time at a specified temperature or a derived value in which an accumulated lethality factor, F0 value, is determined (see 6.5.5).
6.5.2.5 The cycle variables for a contained product sterilization process will depend upon the nature of the process (see Annex D) and shall be identified to determine the instrumentation necessary for a particular sterilization process. Cycle variables which shall be considered include, but are not limited to:
a) time;
b) temperature;
c) pressure;
d) operational factor e.g. chamber circulation system speed to ensure homogeneity of chamber conditions (steam-air overpressure contained fluid sterilization processes, heated water spray water flow rate, water immersion water flow rate).
Conformance is demonstrated by inspection of the technical documentation.
6.5.3 The sensors required to monitor the cycle variables identified in 6.5.2.5 d) shall be specified. The specification for the sensors shall take into account the characteristics identified in 6.5.2.3.
6.5.4 If dates and times are presented, the format in which the date is presented shall be specified.
NOTE The format in which the date or time is presented can be configurable to customer requirements.
Conformance is demonstrated by inspection of the technical documentation.
6.5.5 The units of measurement for each indicated parameter shall be specified.
NOTE The preferred units of measurement are SI units however units of measurement can be configurable to user requirements. Regulatory requirements can apply to the units of measurement indicated.
Conformance is demonstrated by inspection of the technical documentation.
6.5.6 Instruments for measuring the cycle variables temperature, pressure, time and if used accumulated F0 value shall meet the following requirements.
6.5.6.1 Temperature sensors shall be either platinum resistance types conforming with Class A of IEC 60751:2022 or thermocouples conforming with one of the tables specified in Tolerance Class 1 of IEC 60584-1:2013.
NOTE Other sensors of demonstrated equivalence in measurement characteristics can be used.
6.5.6.2 The temperature probe shall have a response time ≤ 5 s when tested in flowing water at a temperature of 95 °C with a velocity of 0,3 (+/- 0,1) m/ sec according to IEC 60751:2022, 6.5.5.
NOTE The following method can also be used to establish the response time:
a) equilibrate the probe to (20 ± 5) °C in air;
b) plunge the probe into a stirred water bath at (95 ± 2) °C;
c) record the temperature rise and calculate the time to reach 90 % of the temperature difference [e.g. (95-20) x 0,9 = 67,5 °C].
6.5.6.3 At least one set of the probe(s) used for control of the operating cycle and for the indication of sterilizer chamber temperature and also the independent probe(s) used to record the operating cycle shall be located at the point identified as the reference measurement point.
NOTE Other probes (e.g. placed inside the contained product) can also be used as part of the control function.
6.5.6.4 At least two independent temperature measuring chains shall be provided such that the failure of an element in one chain will not cause error or failure in the second chain (see Annex B).
6.5.6.5 The temperature measuring chains shall:
a) indicate in degrees Celsius or Fahrenheit;
NOTE 1 In some jurisdictions it is conventional to use Fahrenheit.
b) have a scale which includes the range 50 °C to 150 °C;
c) have a measurement error not exceeding 1 % over the scale range 50 °C to 150 °C;
d) have a resolution not exceeding 0,1 K;
e) ensure a measurement error not exceeding 0,5 K over the temperature range used to establish the lethality of the process;
f) ensure a measurement error not exceeding 0,5 K over the range 100 °C to 135 °C if F0 value accumulation is carried out;
NOTE 2 The temperature measurement error can have a disproportionate impact on the accumulated F0 value for a sterilization cycle because of the logarithmic nature of the calculation.
g) have a temperature error compensation that a measurement error caused by the ambient temperature does not exceed 0,04 K/K.
6.5.6.6 Pressure transducers shall:
a) be absolute pressure transducers;
b) include the range 0 kPa to 400 kPa if the sterilization cycle includes a sub-atmospheric stage;
c) include the range 100 kPa to 400 kPa if the sterilization cycle does not include a sub-atmospheric stage;
d) have a response time for rising pressure ≤ 0,2 s according to IEC 62828-1;
e) have a measurement error for the pressure transducer not exceeding 1,6 % over the scale range 0 kPa to 400 kPa.
6.5.7 At least two independent absolute pressure measuring chains shall be provided such that the failure of an element in one chain will not cause error or failure in the second chain.
Pressure measuring chains shall:
a) indicate in kilopascals or bars;
NOTE 1 In some jurisdictions it is conventional to use pounds per square inch (psi).
b) include the range 0 kPa to 400 kPa absolute pressure;
c) have a resolution not exceeding 1 kPa (0,01 bar);
d) have a maximum permissible measurement error of the whole measuring chain not exceeding 5 kPa after adjustment under the condition of sterilization temperature(s);
e) be calibrated at the following working pressures:
1. specified lowest pressure the process will use if different than atmospheric pressure;
2. ambient atmospheric pressure;
3. maximum working pressure during the plateau period;
f) maximum measurement error at these points shall be smaller than the tolerances established for the operating cycle parameters;
g) have measurement error compensation that a measurement error caused by the ambient temperature does not exceed 0,04 %/K over the scale range 0 kPa to 400 kPa.
6.5.8 Pressurised jacket and steam supply measuring chains
Pressure measuring chains shall:
a) indicate in kilopascals or bars;
NOTE In some jurisdictions it is conventional to use pounds per square inch (psi).
b) have an accuracy of ±1,6 % or better over the scale range 0 kPa to 400 kPa;
c) be graduated in divisions not greater than 20 kPa;
d) have means to adjust in-situ without dismantling the instrument.
6.5.9 The timers in the automatic controller used for the control of the operating cycle or indicating the progress of the operating cycle shall:
a) be graduated in hours, minutes and seconds as applicable;
b) have a measurement error not exceeding +/- 1 s for each defined stage or period of the operating cycle.
6.5.10 Accumulated F0 value control and indicating equipment
6.5.10.1 The accuracy of the accumulated F0 value measurement system, if fitted, shall be established and specified in the technical documentation.
6.5.10.2 The accumulated F0 value indicating equipment shall:
a) be graduated in minutes to 2 decimal places;
b) have a measuring error not greater than that shown in Table 1.
Table 1 — Permitted errors for F0 values
Target F0 value delivered at 121,1oC | Tolerance for F0 values indicated and recorded by the sterilizer’s instruments |
|---|---|
1 | 0,88 to 1,13 |
15 | 13,23 to 17,00 |
30 | 26,47 to 34,00 |
NOTE The tolerances associated with the F0 value accumulation system are dependent upon the accuracy of the temperature and the time measurements (+/- 0,5 K and +/- 1 % time), particularly those arising from within contained product. The accurate determination of accumulated F0 value is critical when used in the calculation of load sterility assurance levels using the bioburden or combined bioburden and reference microorganism methods described in Annex B of ISO 17665:2024. Also see E.6. | |
6.5.10.3 Verification of the accuracy of the F0 value accumulation system shall be determined according to one of the methods described in Annex E.
6.2.1 Indicating devices
6.6.1 The sterilizer shall be fitted with means for indication of the operating cycle parameter(s).
6.6.2 The characters on each indicating device shall be readable by normal or corrected vision at viewing distances between 25 cm and 1 m with a minimum external illumination of 215 +/- 15 lx.
6.6.3 The data sampling rate and the response time of sensors and measuring chains for indicating devices shall be appropriate to represent the sterilization process. The following indication device characteristics shall permit indication of the sterilization process within the specified cycle or process parameters:
a) data sampling rate;
b) measuring chain response time;
c) hysteresis;
d) maximal permissible errors;
e) error caused by changes in ambient conditions.
6.6.4 Each indicating device shall be marked or labelled with a description of its function and location of its sensor(s).
6.6.5 If an indicating device has more than one sensor attached the sensing point along with the measured value at the corresponding sensing point shall be indicated.
6.6.6 Each indicating device shall be provided with a means of adjustment for calibration purposes. The system of adjustment shall be protected against inadvertent re-adjustment by use of an access device.
6.6.7 The sterilizer shall be fitted with status indicators displaying:
a) status of the services necessary to operate the operating cycle safely;
b) sterilizer door(s) locked;
c) operating cycle selected, if applicable;
d) operating cycle in progress;
e) operating cycle stage;
f) operating cycle complete;
g) fault, if present;
h) when the sterilizer door can be opened;
i) operating cycle counter.
Conformance is demonstrated by inspection of the technical documentation.
6.6.8 For operating cycles for test or equipment maintenance purposes, the cycle complete indication shall be different from that of a sterilization cycle.
Conformance is demonstrated by inspection.
6.6.9 A counter shall be provided to indicate the cumulative number of all operating cycles started, including operating cycles in which a fault occurred. The cycle counter shall display a minimum of four digits and shall be protected against tampering or being reset inadvertently.
Conformance is demonstrated by inspection of the technical documentation.
6.6.10 After a fault has been indicated, cycle complete shall not be indicated.
Conformance is demonstrated by inspection of the technical documentation.
6.6.11 If two doors are fitted to the sterilizer the following indicators shall be located at both ends of the sterilizer:
a) a chamber pressure indicating instrument (see 5.7.4);
b) an indication that the doors are closed and locked;
c) a cycle complete indicator.
NOTE The indications can be part of a secondary terminal which is a remote unit that receives process data from the automatic controller.
6.2.2 Recorders
6.7.1 Sterilizers shall be fitted with means to enable the recording of process variables and cycle variables for each operating cycle carried out by the sterilizer. Recorded data shall be sufficient to enable the operating cycle to be judged for the release of sterilized product and for further data processing.
6.7.2 The means fitted to the sterilizer for recording data or printing process records may be either
a) incorporated into the sterilizer; or
b) be a specified interface using a specified data format connecting the sterilizer to an external system.
6.7.3 The recorders characteristics specified in 6.5.2.3 shall permit evaluation of the sterilization process against the specified parameters.
6.7.4 The recorder shall record the temperature from contained product load probe(s) (if used).
NOTE The process variables for a moist heat sterilization process are temperature and holding time, exposure period or accumulated F0 value in the presence of moisture. Moisture is provided by the aqueous liquid within the contained product. The only means by which the process variables temperature and time can be directly measured is by use of a contained product load probe.
6.7.5 The cycle variables for a contained product sterilization process will depend upon the nature of the process and shall be identified to determine the instrumentation and recordings necessary for a particular sterilization process. Cycle variables which shall be considered include, but are not limited to:
a) time;
b) temperature;
c) pressure;
d) operational factor e.g. the rotation speed of the circulation system used to ensure homogeneity of the chamber environment during a steam-air mixture contained fluid sterilization process and the flow rate of the circulating water in a superheated water spray contained fluid sterilization process.
NOTE See Annex D for examples of contained product sterilization processes.
6.7.6 If dates and times are presented, the format in which the date is presented shall be specified.
NOTE The format in which the date or time is presented can be configurable to customer requirements.
6.7.7 The units of measurement for each indicated parameter shall be specified.
NOTE The unit of measurement can be configurable to customer requirements. Regulatory requirements can apply to the units of measurement indicated.
6.7.8 The data recorded shall be identified on the record.
Conformance is demonstrated by inspection.
7.0 Service and local environment
7.1 General
7.1.1 The requirements for services that are not part of the sterilizer but are needed for the sterilizer to perform as intended shall be specified, including but not limited to:
a) the necessary services;
b) the surrounding environmental conditions;
c) the supporting infrastructure.
7.1.2 For a moist heat contained fluid sterilizer the required services may include, but not be limited to:
a) electrical supply;
b) saturated steam supply;
c) lighting;
d) water;
e) compressed air or other specified gas;
f) drains;
g) vacuum;
h) ventilation.
7.1.3 The sterilizer shall be provided with means to isolate each service so they no longer present a hazardous situation if undergoing installation or equipment maintenance. Isolation of a service shall not create a hazardous situation.
NOTE The purpose of a means to isolate a service is so that equipment can be installed or equipment maintenance carried out safely e.g. an electrical power isolator which disconnects all poles, a mains steam valve which isolates equipment from a pressurised steam supply.
7.1.4 Means shall be provided to prevent the ingress of particulates from the services or environment that could affect the performance of the sterilizer or products being sterilized.
NOTE Strainers or filters of a relevant pore size rating can be used.
7.1.5 All service connections to the sterilizer shall be labelled to identify their purpose.
NOTE It is anticipated that the services provided at the point of installation of the sterilizer can also be suitably labelled to identify their purpose.
7.1.1 Sterilizing agent and sterilant
The sterilizing agent shall be generated from the aqueous fluid within the sealed container of the contained product as the temperature rises. The specification for the sterilizing agent falls outside of the scope of this standard.
NOTE 1 In moist heat contained fluid sterilization processes the environment within the chamber is not the sterilizing agent but rather a heating medium which can be, for example, saturated steam, a steam-air mixture, a heated water spray, or water immersion (see BP 2022). See Annex D for examples.
NOTE 2 ISO 17665 provides requirements for the development, validation and routine control of a moist heat contained fluid sterilization process.
7.1.2 Electrical supply
The sterilizer shall be designed to operate with an electrical supply in accordance with IEC 61010-1:2010+A1:2019, 1.4, 4.3.2.5, 6.10 or IEC 60204-1:2018+A1:2021, 4.3, 4.4.3, 4.4.4, 4.4.5 and Clause 5.
NOTE See also 60204-1:2018+A1:2021, Clause 11 for information on enclosures, doors and openings for electrical supplies.
7.1.3 Water
7.4.1 If the sterilizer requires a water supply, the requirements for water to be supplied to the sterilizer shall be specified for each specific use within the sterilizer (e.g. feedwater, service liquid, cooling water, process water).
7.4.2 The specification for the water shall ensure that any contaminants are not present in a concentration that could damage the sterilizer, impair the sterilization process or damage the sterilization load.
7.4.3 Water for process equipment
7.4.3.1 General
The sterilizer shall be designed to operate with water that is of potable quality and supplied at a temperature not exceeding 20 °C and with a hardness value of water (Σ ions of alkaline earth), between 0,7 mmol/l and 2,0 mmol/l. In some circumstances higher feed water temperatures can be used provided the effect on the performance of the sterilizer is known and controlled and is part of the sterilizer specification.
NOTE Regional variations in water supplies can mean that the hardness values of potable water fall outside the given limits and this can cause scaling and corrosion problems.
7.4.3.2 Water used for the generation of steam (steam generator feedwater)
7.4.3.2.1 If a dedicated steam generator is used, the sterilizer shall be designed to operate with steam produced from water free from contaminants at a concentration that can impair the sterilization process or harm or contaminate the steam generator, sterilizer or load.
7.4.3.2.2 If the quality of feed water can affect the operation of the steam generator or quality of steam supplied to the chamber it shall be specified.
NOTE 1 Contaminants which can be considered include but are not limited to iron, cadmium, lead, chloride, phosphate, ammonium, calcium, magnesium, nitrate, sulphate and silicate ions and bacterial endotoxins. In addition, other physicochemical properties can also be considered including pH, conductivity, appearance, oxidisable substances, the residue on evaporation of a defined volume of condensate. Suitable limiting values can be found in, for example, EN 285 and EN 13060.
NOTE 2 Non-condensable gases dissolved in the feed water can cause an increase in non-condensable gases in the steam (see Annex I for reference to suitable test methods).
7.4.3.3 Water used as part of the sterilization process coming into contact with the load
If water is used during the sterilization cycle and comes into contact with the load its quality shall be specified and the sterilizer shall be designed to operate with water of such quality.
NOTE Contaminants which can be considered include but are not limited to iron, cadmium, lead, chloride, phosphate, ammonium, calcium, magnesium, nitrate sulphate and silicate ions and bacterial endotoxins. In addition, other physicochemical properties can also be considered including pH, conductivity, appearance, oxidisable substances, the residue on evaporation of a defined volume of condensate.
7.4.4 If a water reservoir is fitted, the reservoir shall:
a) be fitted with a valve or other device to allow draining of the reservoir and associated pipework;
b) either be large enough to contain sufficient water for the running of a sterilization cycle or the number of consecutive operating cycles specified to be performed with the test load having the maximum water consumption, or be provided with means to refill automatically;
c) be vented and its design shall facilitate cleaning, inspection and filling;
d) be provided with means to indicate if the water in the reservoir is not sufficient for the current sterilization cycle, if no automatic refill is provided;
e) be designed to prevent back siphoning.
7.4.5 The sterilizer shall not be capable of starting an operating cycle if there is insufficient water in the reservoir.
Conformance is demonstrated by inspection of the technical documentation.
7.1.4 Steam
7.5.1 If the sterilizer requires an external steam supply, the requirements for steam to be supplied to the sterilizer shall be specified for each use within the sterilizer (e.g. plant steam/heating steam, processing steam/sterilizing steam, pure steam) and the sterilizer shall be designed to operate with the specified quality of steam.
7.5.2 If boiler additives are permitted to be used during steam generation, permitted additives and their maximum permitted concentration(s) shall be specified to limit potential contamination of steam.
NOTE 1 The specification of boiler additives can take into account possible compatibility considerations for the materials used in the sterilizer construction and any possible adverse effects on the load.
NOTE 2 In modern steam generation and supply systems made of stainless steel the need for additives is usually unnecessary. In such cases purified water can be required and can be supplied as specified in applicable steam boiler codes and regulations.
7.1.5 Vacuum
If the sterilizer requires an external vacuum system to operate as intended, the requirements for the external vacuum system shall be specified.
NOTE Contained product sterilization processes do not always use sub atmospheric stages in the operating cycles (see ISO 17665:2024, Annex D, D.3 through D.5).
7.1.6 Drains
7.7.1 If the sterilizer requires connection to an external drainage system, the requirements for the drainage system shall be specified.
7.7.2 The maximum temperature of fluid released from the sterilizer to an external drainage system shall be specified along with the maximum flow rate of water, air and condensed steam.
NOTE Drainage systems can, for example, be specified as being permanently resistant to 80 °C or greater and resistant to 100 °C for a short period.
7.7.3 Means shall be provided to prevent fluid released from the sterilizer to a drain creating a hazardous situation.
NOTE Some regulations can require the drain to be trapped and vented and not connected to other drains which can cause a back pressure or obstruction to flow. An air break can also be necessary.
7.1.7 Lighting
The user interfaces of the sterilizer shall be designed to allow operation with a minimum external illumination of 200 lx.
NOTE During equipment maintenance additional temporary lighting can be required to allow safe working.
7.1.8 Compressed air
7.9.1 If the sterilizer requires a compressed air supply, the requirements for compressed air to be supplied to the sterilizer shall be specified for each specific use within the sterilizer (e.g. pneumatic operation of valves, door operation).
NOTE For compressed air contacting the load, see 7.10.
7.9.2 When compressed air is used to operate the sterilizer the air quality shall conform with a specified classification described in ISO 8573-1. The specification shall identify a classification regarding particles, dew point and oil contamination
NOTE Attributes which can be considered are freedom from liquid water, filtered to remove solid particles greater than 25 micron and oil droplets greater than 2 micron.
7.9.3 The permissible pressure range for the compressed air supply shall be specified and the flow rate at the minimum.
NOTE A supply pressure range of 5 to 7 bar can be considered.
7.1.9 Air and inert gases
7.10.1 If the sterilizer requires air or inert gases to be admitted to the chamber e.g. as part of a steam-air contained fluid sterilization process, the requirements for the air or inert gas shall be specified in the technical description (see 11.2 b)).
7.10.2 Such air and inert gases admitted to the chamber during the sterilization cycle shall be supplied or treated to ensure that it is free from oil and filtered to remove solid particles greater than 25 microns (see also 5.2.8.2).
7.1.10 Ventilation
The sterilizer shall be designed to operate in an ambient temperature and humidity as specified in IEC 61010-2-040:2020, 1.4.
NOTE The heat transmitted from the sterilizer and from the sterilized load during unloading can contribute to the heat burden of ambient air. This can require the provision of a ventilation system designed and constructed to remove the heat transmitted from the sterilizer and from the load when unloading.
8.0 Emissions
8.1 Electromagnetic emissions
8.1.1 Sterilizers shall conform with IEC 61326-1 regarding electromagnetic emissions.
8.1.2 Sterilizers operating in areas intended for medical electrical equipment or in the vicinity of other sensitive equipment shall be regarded as Class B equipment as specified in IEC 61326-1.
8.1.1 Noise
8.2.1 Conformance with 8.2 is demonstrated by inspection of the technical documentation.
8.2.2 Noise emission from the sterilizer, with the exception of any audible alarm (see 6.4), shall be reduced by design and selection of components with low noise emission levels, particularly at source.
8.2.3 If equipment produces noise (except alarms) at a level which could cause a hazard, the sound pressure level shall be estimated.
NOTE 1 A sound pressure level of 80 dB above a reference sound pressure of 20 µPa is at present regarded by many authorities as the threshold at which a hazard can be caused. Special means, such as the use of protective earpieces, can make a higher level non-hazardous to an operator (see IEC 61010-2-040).
NOTE 2 Also see Reference [45].
8.2.3.1 If the estimate of the sound pressure level is below 60 dB (A), a statement in the technical documentation that the sound pressure level is below 70 dB (A) shall be provided.
8.2.3.2 If the estimate of the sound pressure level is above 60 dB (A), A‑weighted sound power and emission sound pressure levels shall be determined and specified for each type of sterilizer. For testing and calculation ISO 3746 shall apply. The measured sound pressure level shall be provided in the technical documentation.
NOTE 1 Estimation of sound pressure levels can be performed using a hand-held sound meter.
NOTE 2 Different jurisdictions can have local requirements relating to the risks associated with noise, for example EU Directive 2003/10/EC [58].
8.2.4 For a double ended sterilizer the determination shall be carried out at both doors unless it can be demonstrated that noise levels are the same at each.
8.2.5 When conducted (see 8.2.3), the noise emission tests shall be performed during works tests in standard operation with an empty chamber.
NOTE 1 For test and calculation, other methods of demonstrated equivalence can be used. Guidance is provided in ISO 3740.
NOTE 2 Guidance to reduce noise at source is provided in ISO 12100:2010, 6.2.2.2, 6.2.3, and 6.3.4.2.
8.2.6 If specified, the stated emission sound pressure level shall apply for the operator’s position in front of the sterilizer at a distance of 1 m and a height of 1,6 m.
8.2.7 The standard deviation for the sound power and emission sound pressure levels shall be +5 dB in accordance with ISO 3746:2010, Table D.1.
8.2.8 If changes or modification of tested sterilizer and ancillary equipment does not cause additional noise that can cause a hazard (see 8.2.2), further testing and change of the specification can be omitted.
8.2.9 The sound power level for any additional devices supplied for use with the sterilizer shall be indicated in the technical description provided with the device(s).
8.1.2 Exhaust emissions
8.3.1 The removal of fluids (e.g. steam, heated water, air or inert gases such as nitrogen) present within the chamber during the operating cycle shall ensure that a hazardous situation is not created in the immediate work environment where personnel are working without protective equipment (see IEC 61010-2-040:2020, 13.1).
8.3.2 If exhaust emissions from the sterilizer can create a hazardous situation or are harmful to the environment they shall be controlled and, if necessary, discharged via a suitable emission control system.
8.1.3 Heat emissions
8.4.1 Pipework at a temperature greater than 60 °C shall be thermally insulated to reduce heat transmission to the environment except where this will interfere with the function of the sterilizer.
Conformance is demonstrated by inspection.
8.4.2 The maximum heat in Joules transmitted by the sterilizer to the surrounding air during an hour of continuous operation with the sterilization cycle giving the highest emission of heat, shall be specified based on an ambient temperature of (23 ± 3) °C.
Opening the sterilizer and removal of the load after the end of an operating cycle shall be included in the one-hour period.
8.4.3 For the protection against hazards in relation to equipment temperature and to heat sterilizers shall conform with IEC 61010-1:2010, Clauses 4 and 10, as modified by IEC 61010-2-040:2020, Clause 10.
8.4.4 For the protection against hazards related to the spread of fire and resistance to heat, as far as not addressed in IEC 61010-2-040:2021, Clause 9, EN 764-7, EN 14222, EN 13445-1, EN 13445-2, EN 13445-3, EN 13445-4, EN 13445-5 and EN 13445-8, sterilizers and their components shall conform with IEC 60204-1:2016, 6.3.3, 6.4 and Clause 7.
9.0 Test instrumentation
Test instruments used for performance and assessment shall meet the requirements given in Annex H.
10.0 Performance and assessment
10.1 General
10.1.1 The equipment shall at least meet the requirements of this document. It is permissible to exceed the requirements.
NOTE 1 Annex F describes a series on reference tests and loads. These can be used as type tests and works tests and, in some cases, operational qualification tests. They can be carried out on samples of serially produced sterilizers or parts whose design and construction are representative of production units. The tests can also be used to demonstrate the performance of bespoke sterilizers. Their purpose is to check that the design, construction and performance ensure conformity with this document. The sequence of tests is optional unless otherwise specified. Different or additional inspections or tests can be undertaken during the production of individual sterilizers.
NOTE 2 Requirements for installation qualification, operational qualification and performance qualification of a contained product sterilization cycle are given in ISO 17665.
10.1.2 Tests on subassemblies that meet the requirements of the relevant standards specified in this document, and used in accordance with them, shall not need to be repeated during type tests of the whole equipment. If this approach is taken a rationale and justification shall be documented in the sterilizer’s technical documentation.
10.1.3 Conformity with the requirements of this document shall be established by carrying out all applicable tests. A test may be omitted if examination of the equipment and design documentation demonstrates conclusively that the equipment would pass the test. If this approach is taken a rationale and justification shall be documented in the sterilizer’s technical documentation.
10.1.4 If test loads or process challenge devices are necessary in type testing to demonstrate the performance of a sterilization cycle for specific types of load configurations as stated by the intended use, these test loads shall be specified.
10.1.5 Where conformity statements in this document require inspection, this may include examination of the:
a) equipment by measurement;
b) markings on the equipment;
c) information supplied with the equipment;
d) data sheets of the materials or components from which the equipment is manufactured.
In each case, the inspection shall:
1. demonstrate that the equipment meets the applicable requirements;
2. indicate that changes to the sterilizer are needed; or
3. indicate that further testing is required.
10.1.1 Chamber integrity
10.2.1 The chamber shall have no discernible leaks during any stage of a sterilization cycle.
Conformity shall be established by inspection during the progress of a sterilization cycle or by conducting a leak rate test.
10.2.2 A specification of and the acceptance criteria for, the test used to determine the level of leakage from the chamber when it is at super atmospheric pressures shall be documented.
NOTE A method is given in F.6.
10.2.3 If vacuum is used during the operating cycle, a specification of and the acceptance criteria for the test used to determine the level of air leakage into the chamber shall be documented.
NOTE A method is given in F.8.
10.2.4 If vacuum is used during the operating cycle, a description of the test (e.g. a leak rate test at a specified stage of the operating cycle) or device (e.g. air detector) fitted, including its settings and acceptance criteria used to detect any non-condensable gas that can be present in the chamber after the air removal stage of the sterilization cycle.
NOTE The fitted device can also be used to measure the amounts of non-condensable gas carried into the chamber with the steam.
10.1.2 Attainment of conditions - Thermometric
10.3.1 The sterilizer shall be pre-programmed with at least one test operating cycle (empty chamber test) in which the sterilization temperature is 121 °C with a sterilization temperature band of -0/+3 °C and a holding time of at least 15 min.
NOTE An alternative operating cycle which has process parameters similar to those specified in 10.3.1 can be used.
10.3.2 The minimum temperature at which the calculation of accumulated F0 values can commence shall be not less than 110 °C.
10.3.3 If the calculation of accumulated F0 values takes place at a temperature less than 110 °C then the microbicidal effectiveness shall be established and documented.
NOTE See ISO 17665:2024, 5.2 for further information.
10.3.4 The F0 value accumulation system shall accumulate values at time intervals not exceeding 1 s.
10.3.5 If, during the holding time or exposure period the temperature in a container reaches a steady state condition, the F0 value accumulation time interval can be set to 10 s during that period.
10.3.6 The sterilization cycle shall consist of a number of stages. Each stage shall be specified and included in the technical information provided with the sterilizer. This shall include a description of the stage’s purpose, the process variables and cycle variables which shall be employed by the automatic controller to deliver an effective process and the target process parameters and cycle parameters which shall be used by the automatic controller to control the process.
NOTE Greater detail on each stage of a typical contained product sterilization process can be found in Annex D.
10.3.7 If required, air shall be removed by trapping, venting, steam purging, or by means of a vacuum pump(s).
10.3.8 If required water of specified quality shall be admitted to the chamber to a specified level (closed loop system).
10.3.9 If required, compressed air or an inert gas of specified quality shall be admitted to the chamber to achieve a specified pressure.
10.3.10 If required steam shall be admitted to, or be produced in, the chamber to achieve a specified temperature.
10.3.11 The automatic controller shall be programmed to deliver a heating period.
10.3.12 The automatic controller shall be programmed to deliver a specified holding time or a specified exposure period.
10.3.13 The holding time or exposure period shall be controlled by means of one of the following:
a) a timer(s) within the automatic controller initiated by parameters from temperature sensors at the temperature reference measurement point such as the chamber or chamber drain or from within container(s) of the load (see 6.3.1);
b) temperature parameters from a load surrogate; or
c) by a system which calculates the F0 value from a temperature sensor which can be located in a representative container(s) of the load or a load surrogate. If this approach is used the calculation of the F0 value shall only commence when the requirement in 10.3.2 or 10.3.3 has been attained within the load container or load surrogate and shall only be capable of initiating the cooling period when a specified F0 value has been accumulated.
NOTE The heating period and holding time or exposure period will be load specific and can be established during the validation of sterilization cycles processing contained product loads (see ISO 17665).
10.3.14 The automatic controller shall be programmed to deliver a cooling period. The cooling period shall be achieved by either natural or assisted cooling.
10.3.15 During the cooling period the automatic controller shall maintain the door(s) in the locked condition until
a) the timer controlling the door interlock has reached its end point and the systems monitoring the performance of the cooling system indicate that a satisfactory cooling cycle has been carried out; or
b) the door interlock simulator has reached a temperature which will ensure the contents of all the containers comprising the reference load described in the thermometric test for a full load (Annex F) or the proposed production load(s), if known, have cooled to less than 90 °C for plastic or 80 °C for glass containers.
10.3.16 For production loads the timer set point or temperature set point for the door interlock simulator shall be determined during validation.
NOTE ISO 17665 provides requirements for validation.
10.3.17 When assisted cooling is effected by means of a water spray in the chamber, the spray shall be in operation
a) during specified cycle times or periods of the operating cycle;
b) during the heating period and holding time; or
c) exposure period of the operating cycle;
in order to expose the coolant to the sterilizing conditions of the sterilization cycle.
NOTE The coolant spray can be created from the condensate formed during the heating period.
10.3.18 The heat-exchanger for the cooling medium (air or water) shall not be in the cooling mode during the heating period and holding time or exposure period.
10.3.19 Means shall be provided to ensure that there is sufficient coolant when the sterilizer is operated with either an empty chamber or with a small load.
10.3.20 Upon completion of an operating cycle, all liquid cooling medium shall
a) be discharged to waste; or
b) retained in a holding vessel for reuse.
The number of times the cooling medium can be reused shall be validated and controlled via the automatic controller programming.
NOTE 1 This is to avoid build-up of microbial, chemical or particulate contaminants.
NOTE 2 When assisted cooling is achieved by means of a liquid spray within the chamber, it can be necessary to maintain the pressure within the chamber by means of an air overpressure as the steam pressure reduces.
10.3.21 The sterilizer shall achieve the applicable cycle parameters specified for each stage of the sterilization cycle(s) stored within the automatic controller (see 6.2.1.1) throughout the usable chamber space and reference load locations within the specified tolerances.
Conformance shall be established by measuring the specified cycle and/or process parameters at representative position(s)
a) throughout the usable chamber space with the chamber empty;
b) throughout the usable chamber space with the usable chamber space loaded with a reference load(s);
c) within items constituting the reference load(s).
NOTE 1 Suitable reference loads, sensor locations, test methods and acceptance criteria are given in Annex F. Alternative sensor locations to those identified in Annex F can be used provided a justification for the number and location of the measuring positions is documented.
NOTE 2 Specific test load configurations can provide a high challenge for air removal and heating medium penetration into the test load (e.g. baskets of small volume hermetically sealed ampoules, containers of container closures).
10.3.22 Heat exchanger integrity tests
10.3.22.1 This test is designed to check the integrity of the heat exchanger used to heat and cool the circulating cooling medium (air or water) in the chamber. The circuit which is directly heated is called the primary circuit. Water in the primary circuit is assumed to be non-sterile. The circuit which exposes the cooling medium to the load is called the secondary circuit. In recent models of contained product sterilizers the secondary circuit is designed to operate at a higher pressure than the primary to prevent leakage of contaminated water into the chamber.
10.3.22.2 The heat exchanger shall be designed and constructed in a fail-safe manner so that the secondary cooling circuit cannot be contaminated.
10.3.22.3 The heat exchanger shall be tested for integrity according to its instructions for use.
10.3.22.4 The sterilizers instructions for use shall include recommendations for testing the integrity of heat exchangers according to the recommended maintenance frequency.
10.1.3 Microbiological performance
The purpose of microbiological performance assessment is to ensure that a sterilization cycle programmed into the automatic controller is capable of delivering a process which will inactivate biological indicators of specified resistance contained within a reference load(s). Microbiological performance assessment during type testing, works testing, IQ or OQ is not considered necessary for contained product sterilization cycles. Annex F describes microbiological performance assessment methods, based on that described in ISO 17665:2024, B.4.6 which can be used along with suitable reference loads if required.
NOTE Many regulatory authorities and users standard operating procedures require microbiological performance qualification. Validation of sterilization cycles used to process production loads is described in ISO 17665.
10.1.4 Pressure change
10.5.1 The maximum rate of pressure change occurring in the sterilizer chamber during each operating cycle shall be specified.
10.5.2 The calculation of the maximum rate at which pressure rises shall include that caused by the introduction of saturated steam and any other fluids, e.g. air for pressure ballasting, into the chamber.
10.5.3 The calculation of the maximum rate at which pressure declines shall include that caused by the collapse of saturated steam during assisted cooling.
NOTE These maximum rates can have implications for integrity of product including, but not limited to, its sterile barrier system.
10.5.4 The rate of pressure change shall be expressed as the pressure gradient calculated as a rolling average using a rate of measurement of 1 s and time interval for calculations of the rolling average of 3 s.
10.5.5 The method for calculation of the pressure gradient shall be specified and shall be applied to all time intervals within the operating cycle.
10.5.6 The maximum calculated rolling average from at least three replicated operating cycles for an empty chamber condition and a full load condition (see Annex F) shall be expressed as maximum rate of pressure change.
NOTE 1 These determinations can be performed in parallel with other tests.
Conformance shall be established from calculations conducted on specified process records.
NOTE 2 Conformity assessment can be carried out in real time using a recorder, suitably programmed to conduct the pressure change calculations. Alternatively, the recordings of cycle parameters and process parameters from specified process recordings can be transferred to a computerised spreadsheet to enable calculation. It is unlikely that pressure change can be calculated manually with sufficient resolution.
11.0 Information to be supplied
11.1 General
Information to be supplied shall conform with ISO 20417, together with the requirements in 11.2 to 11.6.
NOTE 1 Further requirements on information to be supplied, including the content of labels, markings or use of symbols, can be contained in regulatory requirements or other applicable standards.
NOTE 2 See also Annex G.
Conformance is demonstrated in accordance with ISO 20417 and by inspection of the information to be supplied.
11.1.1 Information to be available prior to purchase
The following information shall be made available to prospective purchasers or contained within a pre-purchase specification:
a) details of the heating medium, including its composition (e.g. saturated steam, steam-air mixture) and any other fluids present in the chamber during an operating cycle (e.g. air used to provide overpressure protection of the load, condensate used as a means of achieving assisted cooling);
b) details of the services required and their quality (e.g. steam, water, gases, electricity, drainage and ventilation);
c) the maximum flow rates of supplied fluids and the minimum and maximum values for the correct functioning of the sterilizer (e.g. in the case of voltage, current, number of phases);
d) the type of loads which can be sterilized (e.g. flexible pouches, semi rigid containers, rigid containers such as sealed ampoules or glass bottles, combination medical devices in pre-formed film pouches);
e) the total duration of the cycle including loading and unloading if an automated system is used;
f) the maximum load(s) per operating cycle;
g) the maximum total chamber leakage permitted (see F.6 and F.8);
h) the design pressure of the pressurised components;
i) a statement that the sound pressure level is below 70 dB (A) if the estimate of the sound pressure level is below 60 dB (A) (see 8.2.3.1), or alternatively, if the estimate of the sound pressure level is above 60 dB (A) (see 8.2.3.2), the A‑weighted sound power and emission sound pressure levels shall be stated;
j) the mean and peak sound power levels generated by the sterilizer, expressed as an A-weighted sound power level;
k) total heat in Joules transmitted to the surrounding air when the sterilizer is operated continuously for one hour in an ambient temperature of (23 ± 3) °C in still air;
l) if the sterilizer is mounted behind facia panelling, then the heat transmitted into the working area in front of the facia and into the plant area behind the facia;
m) the maximum temperature of fluid released from the sterilizer to an external drainage system;
n) requirements for ambient lighting and lighting of equipment maintenance area(s);
o) safety data sheet(s) for any hazardous substance specified for use;
p) the materials of construction e.g. the chamber, insulation, load bearing structures;
q) external dimensions of the sterilizer and its shape, the shipping and packaging dimensions and the required clearances for transportation to the site of installation;
r) shape and dimensions of the usable chamber space e.g. cylindrical, parallelepiped (see Annex C);
s) the type of door(s) fitted and the extent of movement required to fully engage the locking mechanism so as to withstand the design pressure;
t) instructions for handling during transport and storage such as conditions for stability, orientation, temperature, humidity and pressure;
u) installation instructions, including the clearances required for access to the point of installation and overall mass of the sterilizer, the floor loading and the masses of the principal heavy components;
NOTE These are required factors for installation planning.
v) details of consumables and accessories dedicated to the sterilizer;
w) instructions on protective measures to be taken by users, including, if applicable, any personal protective equipment to be provided;
x) cleaning instructions for the chamber and the exterior including the type of agents to be used;
y) any restrictions for installation or operation, including any relevant regulatory classification;
z) a facsimile of the marking on the vessel (see 11.4);
aa) information to show how many operating cycles the sterilizer is designed to deliver during its functional life;
bb) the location of any emergency stop buttons or switches;
cc) any additional instrumentation and controls fitted;
dd) the type of recorder(s) fitted;
ee) the load supporting and handling equipment required;
ff) a statement that the sterilizer shall be installed in an area that has a minimum illumination of 200 lx;
gg) accuracy of the F0 value accumulation system, if carried out by the recorders.
11.1.2 Post delivery information to be provided
Upon delivery of a sterilizer, a document shall be available with the following information:
a) the operating instructions (see 11.6);
b) the works test / factory acceptance test (FAT) report describing tests carried out and their outcomes, including the identified coolest locations during tests on the empty chamber and on any reference loads employed (see Annex F);
c) evidence of verification of each safety function and that the function of each safety protective device and safety accessory and its setting conforms with the specification;
NOTE 1 EN 285:2015, Clause 11 provides detailed requirements for safety, risk control and usability.
d) identification of the software release (if applicable);
e) details of the operating cycles programmed into the automatic controller including the settings for each stage of each cycle characterized by physical conditions such as pressures, temperatures, times and operation of any other equipment needed to deliver a satisfactory operating cycle (e.g. the characteristics of the circulation system to ensure homogeneity of chamber conditions);
f) the location of the reference measurement point for temperature and pressure;
g) the setting of the air detector or process control device if one is fitted;
h) the equipment maintenance instructions, including drawings of pipework, connecting points for services, drawings of the electrical circuits;
i) a schedule of recommended service intervals and a list of spare parts and means of identification;
j) any certificates or declarations confirming conformance to this standard and any necessary regulatory requirements;
k) evidence of verification of the calibration of all measuring systems;
NOTE 2 For measurement traceability and estimation of measurement uncertainty see ISO/IEC 17025:2005, 5.4.5, 5.5.4 and 5.6.
l) instructions for disposal of the packaging of the sterilizer which shall also be clearly indicated on the outside of the packaging.
NOTE 3 This can be in the form of symbols, explained within the document, indicating, for example, recyclability.
11.1.3 Marking
11.4.1 The following marking(s) shall be clearly visible and shall be permanently affixed to the equipment frame or body:
a) If applicable, the unique device identification number (UDI);
NOTE 1 The UDI is a recognised global coding system.
b) electricity supply rated voltage, rated frequency, maximum current or power;
c) maximum operating pressure, design pressure and hydrostatic test pressure;
d) the design temperature;
e) regulatory registration identification;
NOTE 2 Regulatory requirements or specific standards can require additional marking(s).
f) warning symbols;
g) the number and date of the version of this document to which conformity is claimed;
h) the name of the manufacturer of the vessel;
i) the unique identification number such as the serial number of the sterilizer;
j) the date of manufacture;
k) the vessel identification mark of the manufacturer or his agent;
l) any statutory marking required;
m) a facsimile of this marking shall accompany the documentation described in 11.2 q).
11.4.2 Pipework, indicating and operating devices shall be identified as to their function.
11.1.4 Label
Each sterilizer shall be labelled with, as applicable:
a) safety precautions to be taken for operating the door(s);
b) safety precautions to be taken to prevent burns from high temperature;
c) applications of the sterilizer;
d) warnings and precautions.
11.1.5 Instructions for use
The instructions for use for each sterilizer shall include:
a) name and full address of the manufacturer;
b) common name, the manufacturer’s type and model designation;
c) clear description of the intended use of the sterilizer;
d) general description of the sterilizer;
e) description of the available sterilization cycle(s), their recommended settings, their intended application range and restrictions for use, if applicable;
f) description of the types of sterilization load(s), load configuration and appropriate loading volume if applicable;
g) specified process parameters and cycle parameters for the sterilization process if applicable;
h) details of any additional operating cycles provided by the automatic controller if applicable;
i) name and address of the holder of the regulatory approval;
j) warnings and precautions, including a comprehensive list of residual risks;
k) information required by regulatory requirements;
l) instructions for the safe and effective operation of the sterilizer, including:
1. safety precautions to be taken during routine use;
2. safety precautions to be taken for operating the door(s);
3. safety precautions to be taken to prevent burns from high-temperature;
4. considerations for loading (load size, type of materials, load configuration);
5. means by which sterilization cycles programmed into the automatic controller can be selected;
6. means by which a failure to satisfy sterilization process parameters can be detected and the recommended actions;
NOTE Specific procedures can be identified by the user for handling loads which have been subjected to an unsatisfactory sterilization cycle.
7. means by which an error in the monitoring, recording, or controlling of the process parameters can be detected and the recommended actions;
8. instructions for inspection and routine equipment maintenance, including a schedule for implementing inspection and routine equipment maintenance procedures;
9. cleaning procedures with a caution that these procedures should be carried out by trained personnel using appropriate personal protective equipment.
11.1.6 Technical description
The technical description for the sterilizer shall include:
a) name and address of manufacturer;
b) the common name, the manufacturer’s type and model designation;
c) serial number;
d) year of manufacture;
e) unique device identification;
f) electricity supply rated voltage, current type, rated frequency, maximum current or power;
g) design pressure and maximum operating pressure and hydrostatic test pressure;
h) if applicable, regulatory registration identification or mark signifying regulatory approval;
i) requirements for external services;
j) instructions for the installation and installation qualification of the sterilizer, complete and comprehensive enough to ensure the safe and effective operation of the equipment, including such information as the required building system services and the type of materials to be used for installation, including:
1. assembly, installation and connection instructions, including drawings, diagrams and the means of attachment, and the specified requirements for the installation area;
2. details of the services required for supply, drainage and ventilation;
3. the design of the drainage connection which will prevent back pressure or obstructions to flow;
4. the maximum temperature of fluid released from the sterilizer to an external drainage system;
5. clearance required to allow opening of the door(s) and loading and unloading operation of the sterilizer;
6. if applicable, provisions necessary to ensure the mechanical stability of the device during installation, operation, equipment maintenance and service.
k) instructions for inspection and routine equipment maintenance;
l) equipment maintenance interval or timetable and description of routine equipment maintenance procedures;
m) schedule for implementing inspection by the authority having jurisdiction and explanation for routine self-inspection;
n) specific directions concerning the equipment maintenance of critical components, such as filters, recorders, steam separators or traps, valves, and safety valves;
o) list of spare parts replaceable by the user;
p) list of special tools necessary for equipment maintenance;
q) if applicable, description of the recommended procedure for draining and decontaminating the water supply reservoir;
r) declaration that the sound pressure levels are below 70 dBA or if above 60 dBA, the measured sound pressure levels;
s) name and telephone number or other contact information of an authorized service agent or representative;
t) dimensions of the usable chamber space;
u) details of the heating medium;
v) external dimensions of the sterilizer and the floor loading;
w) instructions for handling during transport and storage such as conditions for stability, orientation, temperature humidity and pressure;
x) details of consumables and accessories dedicated to the sterilizer;
y) the total heat in Joules transmitted by the sterilizer to the surrounding air during an hour of continuous operation with the sterilization cycle giving the highest emission of heat, based on an ambient temperature of (23 ± 3) °C;
z) requirements for ambient lighting and lighting of equipment maintenance area(s);
aa) instructions on protective measures to be taken by users, including, if applicable, any personal protective equipment to be provided;
bb) cleaning instructions for the chamber and the exterior including the type of agents to be used;
cc) any restrictions for installation or operation;
dd) statement that materials used in the sterilizer which can come in contact with saturated steam, the heating medium or carrier fluids do not react to an extent that material deterioration could affect the operation of the sterilization cycle, have a detrimental effect on the materials of the sterilizer or chamber accessories, or create a hazardous situation;
ee) maximum rate of pressure change in an operating cycle.
(informative)
Background to the development of ISO 19253- Background
A.1.1 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 (e.g. 1 ml) sealed glass ampoules to large volume (e.g. >1 l) sealed plastic bottles or flexible pouches. Examples of product would be 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 facilities, such as larger regional hospitals, may also have sterile fluids production units. Wherever produced, sterile aqueous liquids in sealed containers, which may 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 water spray in order to heat the contained product to sterilizing temperatures.
A.1.2 ISO/TS 22421 is a general technical specification for any sterilizer used for the terminal sterilization of medical devices. During development of the technical specification, many national and regional standards and guidance documents were consulted in order to ensure the content of ISO/TS 22421 was comprehensive in reflecting the content of currently published documents. Furthermore, during development and in order to respect the various opinions and comments expressed, content was sufficiently general to allow a degree of interpretation by document users. Upon completion, it was generally agreed that this new standard could form the basis of a whole series of documents covering specific sterilization modalities thereby acting as a template for the future development of specific sterilizer standards. In line with this concept, relevant CEN sterilizer standards will be formatted using ISO/TS 22421 as a template.
A.1.3 In the United Kingdom the British Standards Institute published the first edition of BS 3970-2 in 1991 which covered steam sterilizers for aqueous fluids in sealed rigid containers. During the revision of BS 3970-2 an effort was made to mirror the format of ISO/TS 22421. However, noting that the developing standard spanned a variety of application areas and had an international perspective, BSI advanced a proposal for an ISO new work item which was ultimately accepted.
A.1.4 This document for contained product moist heat sterilizers is complementary to ISO 17665 for moist heat sterilization processes.
A.1.5 Sterilizers used for the terminal sterilization of aqueous liquid containing health care products in sealed containers are used both in health care facilities and industrial settings. Such sterilizers can 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 may also be found. An example can 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 sufficiently 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, large steam sterilizers), contained product sterilizers are different in terms of construction and operation thus warranting the need for a separate standard.
- Market relevance and extant standards and guidance
Sterilizers used for the terminal sterilization of aqueous liquid containing health care products in sealed containers are used globally in both health care facilities 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, British Pharmacopoeia and 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 Technical Report 1 and Technical Report 48). 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 aqueous liquid containing health care products in sealed containers would provide a global commonly agreed approach both for manufacturers and users of such sterilizers.
(informative)
Illustrations of the interrelationship between control and recording- General
This annex provides examples of configurations of the relationships between control and recording of a sterilizer to illustrate potential approaches to conforming with Clause 6.
In developing the illustrations, the following criteria were identified as relevant:
a) adequately reflecting the state of the art and the concept for "independent recording" of the process data, as established in current equipment standards for reprocessing of medical devices;
b) not being design restrictive, independent of its informative character;
c) not superseding published sterilizer standards requirements (see 1.0);
d) providing consistency in its details with the requirements given in the normative text;
e) consistently using the terminology as defined in this document and ISO 11139.
- Illustration 1
B.2.1 Figure B.1 provides the first example of a potential configuration of control and recording.
Key
A/D analogue to digital conversion
x1 to xj measurements
<graphic>
</graphic> data flow
<graphic>
</graphic> control flow
<graphic>
</graphic> software or hardware modules / option of separated modules
Figure B.1 — Illustration 1 of the interrelationship between control and recording
[SOURCE: Adapted from ISO/TS 22421:2021]
B.2.2 Figure B.1 is guided by some basics which are considered essential and helpful for understanding of the monitoring and control concept as specified in this document.
The understanding of "independent monitoring" diverges between different experts. It can be helpful to differentiate between:
a) monitoring systems for high-risk applications, which require full (or multiple) redundancy of the complete control and monitoring systems (mirroring), combined with a sophisticated process evaluation and supervising system (e.g. "watch dog"), which allows immediate fault detection, alarms, and eventually automated corrective actions for continued (non-interrupted) basic operation.
NOTE Such systems are typically used in, for example, life support systems in medical intensive care units or in space applications.
b) monitoring systems providing redundant measurement of essential parameters using independent monitors (measuring chains) for control and recording of essential process parameters, combined as well with a process evaluation and supervising system (e.g. "watch dog"), which allows fault detection and alarms, followed, if applicable, by a controlled reset of the system into a safe status and allows proper documentation of all details for later evaluation and consideration.
B.2.3 Consequently, the concept:
a) distinguishes between cycle control, data processing and the user interfaces (controls, indication, recording and printing);
b) has a focus on processes (hardware or software), rather than on hardware components;
c) allows flexible separation of cycle control from redundant data collection and processing, independent from the design several modules may exist;
d) has a focus on flows of information, which do not limit the implementation of the identical (redundant) functions but allows a specific segregation of functional modules and processes;
e) indicates an exchange of information between two "independent processes" and identification of unintended deviations helps minimizing risk. An example is the control of a sterilizer that may react to a deviation between the datasets of process control and independent reference measurements and ensures:
1. the measured difference should be detected as a failure;
2. the detected failure should be indicated and recorded;
3. the process control should be able to react to this deviation;
4. neither the process control nor an action at the control panel are able to modify the independent recording.
Modern software and hardware use concepts like "events" or "data tunnelling", what is addressed by directed streams of information and a distinction between "Data flow" and "Control flow" (commands).
- Illustration 2
Figure B.2 provides the second example of a potential configuration of control and recording.
Key
A/D analogue to digital conversion
x1 to xj measurements
<graphic></graphic> data flow
<graphic></graphic> control flow
Figure B.2 — Illustration 2 of the interrelationship between control and recording
[SOURCE: Adapted from ISO/TS 22421:2021]
The above diagram is one illustration of the principles described below.
a) Means is provided to ensure that a failure or deviation of sterilization cycle control does not remain undetected and that a defective cycle does not appear effective. This is achieved by comparative analysis between data used for cycle control and independently acquired data. The comparison is performed for, at least, each process and cycle variable as defined by the sterilizer manufacturer (for example, temperature of the chamber or load, pressure in the chamber, time, concentration of sterilizing agent, etc.).
b) The means by which control and independent data are acquired may differ. For example, the temperature, pressure or sterilizing agent concentration data may be produced by different type of sensors and/or methods.
c) A/D conversion of cycle control data and independent monitoring data is segregated.
d) Processing of control data and independent data may be segregated or share common hardware or software module. In the second case, design avoids misleading interference between the two flows of data.
e) Failure detection by comparative analysis of cycle control data and independent data is performed automatically and/or by analysis of recorded, displayed or printed data by a certified operator.
f) Records of independent data, results of failure analysis and optionally control data are stored in accordance with local requirements.
- Illustration 3
- General
- Illustration 3
Figure B.3 provides the third example of a potential configuration of control and recording.
Key
A/D analogue to digital conversion
x1 to xj measurements
<graphic></graphic> data flow
<graphic></graphic> control flow
<graphic>
</graphic> segregated software modules
a Refer to corresponding requirement subclause.
Figure B.3 — Illustration 3 of the interrelationship between control and recording
[SOURCE: Adapted from ISO/TS 22421:2021]
- Main objectives
Means is provided to ensure that a failure in a control function does not lead to a failure in recording of process parameters such that an ineffective process appears effective. This is achieved by the use of segregated systems and through failure detection that identifies any discrepancies and indicates a fault.
Independence can be achieved by physical or logical segregation and involve one or more microcontrollers. Modules can be divided into more submodules as long as they remain segregated from the other modules.
- Control data processing system
The control data processing system is segregated from the independent data (see 6.3.2). This system receive data from sensors and AD-converters physically different from the independent sensors (see 6.3.1). The system converts the raw data to data scaled in engineering units and may include provisions for filtration, linearization, correction and calibration.
- Independent data processing system
The independent data processing system is segregated from the control data (see 6.3.2). This system receives data from sensors and AD-converters physically different from the process control sensors (see 6.3.1). Cycle parameters and process parameters critical for process efficacy and safety are monitored. The system converts the raw data to data scaled in engineering units and may include provisions for filtration, linearization, correction and calibration.
- Cycle control function
The cycle control function receives control data (see 6.3.3) and includes the main logics used to direct the equipment sequentially through required stages of the cycle in response to programmed cycle parameters. The control function operates valves, timers, proportional integral derivative (PID)-controllers and pumps, and makes decisions at various positions during the cycle for example when parameters are reached or timers have elapsed.
- Means for failure detection
A system for failure detection is critical for the process efficacy or the safety. Failures are generated if the parameters differ from the specified conditions. This system receives both control and independent data (see 6.3.5).
- Data retention module
The data retention module compiles and stores control and independent data and informative data for identification, time stamps, phase shifts and notification of failures when they occur. Records are generated periodically, during phase shifts and at extreme points in the process. The data are submitted for recording or printing. This module includes functionality for submittal at a later stage, if data transfer to the recorder or printer is temporary out of service.
- Controls and indicating devices
User interfaces with controls and indicating devices are used for visible, audible and tactile interaction with operators to perceive and interact with the process. Indication can be shown as a physical property, such as temperature, pressure, time and concentration, or just as distinct information displayed as something being active, inactive, ready, open or closed. The user interfaces can be on the sterilizer or in a remote operating facility. Controls can be any button or switch including soft buttons on an operating panel. Faults are indicated and result in audible or visible alarms. Stop or automatic progression after faults can be decided by the control function (see B.4.5) or a result of interaction through indication and controls.
- Recorder
Storage of process records from the data retention module described in B.4.7 can be directly with devices connected to the sterilizer, or remotely on a network drive (see 6.3.6). Process records may also be handled by an external SCADA system.
NOTE SCADA is supervisory control and data acquisition. SCADA is a collection of both software and hardware components that allow supervision and control of plants, both locally and remotely. This can include handling of goods flow in the health care premises locally or regionally.
- Optional printer
Printing of process records can be directly with devices fitted on the sterilizer, or remotely on a network printer (see 6.3.7).
(normative)
Methods for the determination of the dimensions of the sterilizer chamber and the usable chamber space- Cylindrical chamber
- Dimensions of the sterilizer chamber
- Cylindrical chamber
C.1.1.1 The chamber depth/length shall be determined by taking measurements as follows:
a) from the internal surface of the door to either:
1. the inner surface of the end-plate, if its surface is flat (L, Figure C.1); or
2. the beginning of the curve of the end-plate if its surface is concave (L, Figure C.2);
b) if the chamber has a flat door at each end, between the internal surfaces of the two doors (L, Figure C.1);
c) if the internal surfaces of the doors are convex to the chamber, from the crown of the convex portion of the door(s) or any projection attached to it (L, Figure C.3).
C.1.1.2 The chamber diameter shall be determined by calculating the average of three measurements taken:
a) 100 mm in from the beginning and end point for the measurement taken for determining chamber length (D1 and D3, Figure C.1 or Figure C.2 or Figure C.3);
b) at the midpoint along the length of the chamber (D2, Figure C.1 or Figure C.2 or Figure C.3).
Key
C/L centre lines
D diameter (mm)
L length (mm)
Figure C.1 — Determination of the dimensions of a chamber with a flat door and endplate
Key
C/L centre lines
D diameter (mm)
L length (mm)
Figure C.2 — Determination of the dimensions of a chamber with a flat door and concave endplate
Key
C/L centre lines
D diameter (mm)
L length (mm)
Figure C.3 — Determination of the dimensions of a chamber with a convex door and flat endplate
- Dimensions of the usable chamber space
The dimensions of the usable chamber space shall be calculated from measurements of the diameter and length of a theoretical cylinder which could be inserted and removed from the chamber without obstruction or having to dismantle any part of the sterilizer assembly.
NOTE The definition of a theoretical cylinder which can be inserted or removed from the chamber space takes into account any protrusions into the chamber, such as steam entry port baffle plates, sensor entry ports, chamber functional furniture e.g. circulating fans, curvature of the endplate, which can obstruct insertion or removal and therefore reduce the usable chamber space.
- Parallelepiped chamber
- Dimensions of the sterilizer chamber
- Parallelepiped chamber
C.2.1.1 All measurements shall exclude corner radii.
C.2.1.2 The chamber width and height shall be determined by measuring the distance between the parallel surfaces making up the side walls of the chamber (width) and the floor and ceiling surfaces of the chamber (height).
C.2.1.3 The average of three measurements of height and width shall be taken such that the measurement passes through the geometric centre line of the chamber as follows:
a) 100mm in from the beginning and end point of the measurement taken for determining chamber length (H1 and H3 for height, W1 and W3 for width, Figure C.4);
b) at the mid-point along the length of the chamber (H2 for height and W2 for width, Figure C.4).
C.2.1.4 The chamber length (L) shall be determined according to C.1.1.1 a), b) or c).
Key
C/L centre lines
L length (mm)
H height (mm)
W width (mm)
Figure C.4 — Determination of the dimensions of a parallelepiped chamber
- Dimensions of the usable chamber space
The dimensions of the usable chamber space shall be defined by the width, height and length of a theoretical parallelepiped shape which could be inserted or removed from the chamber without obstruction or having to dismantle any part of the sterilizer assembly.
NOTE See C.1.2 NOTE.
(informative)
Examples of contained product sterilization processes and an explanation of the stages and terminology associated with such processes- Examples of contained product sterilization processes
D.1.1 j of ISO 17665:2024 describes some examples of moist heat sterilization cycles which can be used as contained product sterilization processes.
This includes:
a) steam-air mixtures (to provide an overpressure) sterilization cycles (ISO 17665:2024, D.3);
b) water spray sterilization cycles (ISO 17665:2024, D.4);
c) water immersion sterilization cycles (ISO 17665:2024, D.5).
D.1.2 Steam-air mixtures sterilization cycles
D.1.2.1 This sterilization cycle is primarily used for contained product where at certain stages in the cycle the pressure within the container exceeds the pressure within the chamber. This can result in fracture of the container or loss of integrity of the seal; to compensate for this an overpressure is used.
For such contained product, several sterilization processes are available to ensure that the pressure on the outside of a product balances the pressure on its inside.
D.1.2.2 During the heating (conditioning) stage of the sterilization cycle steam is admitted to the chamber whilst the atmospheric air remains. Steam continues to enter the chamber until the prescribed sterilization temperature or specified temperature is attained. If the entrapped air is insufficient to provide a sufficiently large overpressure to protect the product, compressed air or nitrogen is introduced. Circulation of the heating medium is normally required to maintain a uniform environment.
D.1.2.3 During the plateau period the heating medium within the chamber continues to be circulated and the sterilization temperature or specified temperature maintained for a prescribed time or until a specified F0 value has been achieved while ensuring the chamber's overpressure balances the pressure inside the container.
D.1.2.4 During the cooling (re-conditioning) stage the load temperature is reduced by using cooled compressed air or a cooled water spray. Heat exchangers can be used to cool the cooling medium before it is transferred to the chamber. During this stage, damage to the contained product from rapid de-pressurization of the chamber is prevented by introduction of compressed air or nitrogen. The required overpressure which ensures that the pressure on the outside of the container balances that inside, is then maintained in the chamber until the contained product has been sufficiently cooled and it is then vented to atmosphere.
D.1.3 Water spray sterilization cycles
D.1.3.1 This cycle is used for contained product and utilises a spray of heated water to heat the load.
D.1.3.2 During the water filling (conditioning) stage at the beginning of the sterilization cycle, a quantity of water is introduced into the sterilizer or produced as condensate from the steam supplied to the chamber. It is then sprayed over the product.
D.1.3.3 During the heating (conditioning) stage the load is heated by either introducing steam and air into the circulation system or by heating the spray water by passage through a heat exchanger whilst simultaneously introducing compressed air into the chamber to provide an overpressure which ensures that the pressure on the outside of the container balances that inside.
D.1.3.4 During the plateau period the circulation system is operated and the circulating heated water and contained product is maintained at the required sterilizing temperature or specified temperature for a prescribed time or until a specified F0 value has been achieved while ensuring the chamber's overpressure balances the pressure inside the container.
D.1.3.5 During the cooling (re-conditioning) stage the pressure in the chamber is maintained by compressed air or nitrogen and the contained product is cooled as the temperature of the circulating water is cooled at a controlled rate. The chamber is de-pressurized when the contained product has been reduced to a specified temperature.
D.1.4 Water immersion sterilization cycles
D.1.4.1 This cycle is used for contained product which is completely immersed in water throughout the sterilization cycle as it is heated, held and then cooled.
D.1.4.2 During the water filling (conditioning) stage at the beginning of the sterilization cycle, a quantity of water is introduced into the chamber so that the load is completely immersed. The water is then circulated around a closed loop system which includes a heat exchanger which can heat or cool the water.
D.1.4.3 During the heating (conditioning) stage the immersion liquid and load is heated to the required sterilizing temperature or specified temperature by pumping the water through the heat exchanger.
D.1.4.4 During the plateau period the circulation system continuously operates so that the circulating heated water and contained product is maintained at the required sterilizing temperature or specified temperature for a prescribed time or until a specified F0 value has been achieved.
D.1.4.5 During the cooling (re-conditioning) stage the immersion liquid and load is cooled to the required specified safe temperature by pumping the water through the heat exchanger. At the end of the cooling stage the circulating water is either discarded or returned to a holding tank for further use.
- An example of the stages which can be used in a contained product sterilization cycle
- Stage 1: preliminary actions
- An example of the stages which can be used in a contained product sterilization cycle
Preliminary actions are carried out in the sterilizer preparing it for subsequence stages. This can include the following actions.
a) Removing air from the chamber by trapping, venting, steam purging, or by means of a vacuum pump(s) (active air removal).
b) Leaving air in the chamber or adding additional compressed air or inert gases to act as an over-pressurising gas preventing container fracture or deformation. This is often termed ballasting.
c) Adding water of specified quality to the chamber to a specified level for water spray or water immersion sterilization processes (closed loop systems) in which water is continuously spayed over the load to hasten its heating or where containers are immersed in a body of water. Water sprays may also be used during the cooling period to accelerate the rate of cooling, the water being passed through a heat exchanger.
d) Steam is admitted to the chamber or is produced in the chamber to a specified temperature and pressure so as to begin to heat the load. The temperature of the steam can be within the sterilization temperature band or at a higher specified temperature in order to hasten temperature attainment within the load but should not cause damage to the load. The steam can also be added at a controlled ramping rate to achieve a controlled heating rate within the load.
- Stage 2: heating period
During this stage:
a) all parts of the chamber are exposed to the heating medium;
NOTE 1 The temperature in the chamber can be within the sterilization temperature band, at a higher specified temperature, at some other specified temperature found in the process specification or subjected to a pressure rise ramping rate.
b) the load is heated to reach
1. a specified sterilization temperature;
2. a lower specified temperature at which point F0 values begin to be accumulated by the automatic controller.
NOTE 2 The minimum temperature at which this begins is normally 110 °C but lower temperatures can be used if the microbiological lethality is established.
- Stage 3: holding time or exposure period
D.2.3.1 If a sterilization cycle is being used which employs a fixed sterilization temperature for a specified holding time (e.g. 121 °C for 15 min) then during this stage the temperature of all parts of the chamber exposed to the heating medium, and the aqueous liquid in all containers comprising the load, and any recirculating water, will be within the sterilization temperature band (e.g. -0/+3 °C).
D.2.3.2 If the sterilization cycle being used does not employ a fixed sterilization temperature for a specified holding time then the exposure period will be from when the automatic controller begins to accumulate F0 values. The containers in the load will be allowed to heat up and when a defined F0 value is reached the cycle progresses to the next stage, normally the cooling period. The accumulated F0 values will have a relationship to the sterility assurance level specified for the load.
- Control of stages 2 and 3
Stages 2 and 3 can be controlled by means of one or more of the following:
a) a timer(s) within the automatic controller initiated by parameters from temperature sensors within the chamber, chamber drain or within container(s) of the load (see 6.3.1);
b) temperature parameters from a load surrogate system; or
c) by a system which calculates the F0 value from a temperature sensor which can be located in a representative container(s) of the load or a load surrogate. If this approach is used the calculation of the F0 value only commences when a temperature of 110 °C has been attained within the load container or load surrogate system and is only capable of initiating Stage 4, cooling period, when a specified F0 value has been accumulated.
- Stage 4: cooling period
D.2.5.1 When the holding time is complete or the parameters of the exposure period have been achieved, the cooling period begins. The load is cooled to a temperature low enough not to cause a hazard when removed from the chamber. Load cooling can be either by natural or by assisted cooling.
D.2.5.2 In natural cooling mode, when the cooling period begins the steam supply to the chamber is shut off and the sterilizer and its load allowed to cool to the specified safe temperature by natural heat loss. This may take several hours to complete and is only suitable for loads with high thermal stability.
D.2.5.3 In assisted cooling mode the load is cooled using an active means of removing heat from the load. Depending on the sterilization cycle (see D.1.1) the fluid remaining in the chamber after stage 3 is over is passed through a heat exchanger and circulated over the load accelerating the rate of cooling. The cooling fluid could be a cooled gas, a water spray or the immersion fluid. The benefit of using active cooling is that a more rapid and homogeneous cooling rate can be achieved throughout the load and the rate of cooling can be controlled.
D.2.5.4 The cooling period can be controlled by a timer set in the automatic controller or a temperature sensor mounted within a simulator. During the cooling period the chamber door(s) will remain locked until the cooling period timer has reached its end point or the simulator indicates that the load temperature will be less than 90 °C for plastic loads or 80 °C for glass loads (see Annex J). The cooling period timer or simulator temperature setting is load specific and is established during validation (see ISO 17665) or works testing when reference loads are used.
D.2.5.5 When assisted cooling is effected by means of a spray in the chamber, the spray is in operation throughout Stages 2 and 3 of the operating cycle in order to expose the coolant to the sterilizing conditions of the sterilization cycle.
- Terminology associated with contained fluid sterilization cycles
D.3.1 Some contained product sterilization cycles utilise heated water which is sprayed over the load or the load is immersed in a body of heated water. In such processes the heated water is maintained at a high temperature in the liquid phase by virtue of the fact that the chamber is at a high pressure either with steam or a steam-air mixture (see ISO 17665:2024, Annex E). These processes have a variety of synonyms including, for example, hot water under pressure processes, hot water spray, hot raining water process, water cascade sterilization, water deluge, hot water shower, water spray, spray fluids, circulating water, water sprinkle, water immersion, water submersion.
D.3.2 The term superheated water spray or immersion processes is often used to describe the sterilization cycles in which liquid water is used as a heating medium. In this respect the term superheated water is water in the liquid phase above 100 °C requiring an overpressure to maintain this state as the liquid is circulated around the system. The term superheated water should not be confused with the term superheated steam, which is steam which has been heated to a temperature above the saturation temperature at a given pressure described in steam tables (see ISO 17665:2024, Annex E and References [47] and [50]).
D.3.3 Some contained product sterilization process provide a sterilization cycle in which a non-condensing gas such as air or nitrogen is retained within or added to the chamber in order to provide an overpressure which helps prevent containers bursting or becoming deformed during the process. These processes have a variety of synonyms including, for example, steam-air mixtures also known as SAM processes, air over pressure, cover pressure, compensating pressure, counter pressure, support pressure or fan (circulation device) circulation. It should also be noted that the gas overpressure used in these processes can be present throughout the whole of the sterilization cycle or introduced at specific stages, for example, the cooling stage in order to compensate for the reduction in chamber pressure as the steam in the heating medium condenses. When steam air/gas mixtures are used the sterilizer will normally have some means of ensuring homogeneity of the heating medium in the chamber by use of, for example, a mechanically, magnetically coupled or electrically driven circulation device.
D.3.4 Some contained product sterilizers utilise “simulators”, or “load surrogate devices”, or both. Simulators are devices which are installed as a permanent fixture in the sterilizer and are equipped with a temperature sensor which provides data to the automatic controller. During works testing or validation the simulator set point temperature will be determined which ensures the door interlock does not allow opening until the load is at or below 90 °C for plastic containers or 80 °C for glass containers. The simulator can be constructed from a durable material which will retain its thermal properties for the life span of the sterilizer or can be a serviceable component which will be replaced during equipment maintenance.
Load surrogate devices can be actual containers filled with simulated product into which a flexible probe is inserted which provides temperature data to the automatic controller allowing control and monitoring of the sterilization cycle and accumulation of F0 values. The load surrogate device can also be fixed in a convenient location within the chamber and made from a durable material which will retain its thermal properties for the life span of the sterilizer or can be a serviceable component which will be replaced during equipment maintenance.
(informative)
Verification of the sterilizer’s F0 value accumulation system (if fitted)- General
E.1.1 This annex specifies methods for demonstrating that the F0 value accumulation system calculates F0 values within acceptable tolerances (see Table 1).
NOTE Other methods can be used provided they are shown to have equivalent accuracy (see Table E.1 and Table 1).
E.1.2 The accuracy of the F0 value accumulation system can be established using one of the three methods described in E.2, E.3 or E.4.
E.1.3 The minimum temperature at which the calculation of accumulated F0 values can commence will normally be not less than 110 °C. However, if the calculation of accumulated F0 values takes place at a temperature less than 110 °C for specified and documented reasons then the microbicidal effectiveness will be established and documented (see ISO 17665:2024, 5.2).
NOTE For sterilization processes based on the inactivation of the natural bioburden on the product or on the inactivation of bioburden and reference microorganisms, accurate determination of the accumulated F0 value is critical when calculating the sterility assurance level of the product (see ISO 17665:2024, Annex B).
- Method for establishing the accuracy of the F0 value accumulation system using an in-situ approach
- Introduction
- Method for establishing the accuracy of the F0 value accumulation system using an in-situ approach
In this approach the sterilizer’s load temperature sensor(s) and one from a test instrument (see Annex H) are placed within a 1 l bottle containing water at a temperature less than 30 °C. An operating cycle is carried out and recorded by the sterilizer’s recorder and the test instrument. Upon completion of the operating cycle the accumulated F0 values are compared for conformance with the acceptance criteria.
- Apparatus
E.2.2.1 Glass bottle, of nominal capacity 1 l, conforming with ISO 8536-1.
E.2.2.2 Independent test instrument with F0 calculation capability (see Annex H).
E.2.2.3 If the test instrument does not have F0 value calculation capability, it should have the ability to export recorded data sets in a format which can be imported into spreadsheet software so that F0 values can be calculated (see Annex H).
- Procedure
E.2.3.1 Install the test instrument (see Annex H).
E.2.3.2 Place 1 L of water at less than 30 °C in the bottle. Insert the sterilizer’s load temperature sensor(s) and the sensor of the test instrument so that the sensing points of each are in close proximity and are placed in a documented challenge location within the bottle. Seal the bottle.
E.2.3.3 The response time of the test instrument’s temperature sensor(s) should be within +/- 2,5 % of the sterilizer’s load temperature sensor(s).
NOTE If necessary, a thermal shield can be placed over the test instrument’s temperature sensor to ensure response time equivalence to the sterilizers load temperature sensor (see E.2.3.3).
E.2.3.4 Select and perform an operating cycle with a nominal sterilization temperature of 121 °C and a holding time of 15 min and note the F0 value shown by the sterilizer’s recorder and the test instrument’s recorder at the commencement of the plateau period, the holding time and the end of the holding time.
E.2.3.5 Repeat E.2.3.2 and E.2.3.4 three times, filling the bottle with fresh water each time.
E.2.3.6 Select a second operating cycle with a nominal sterilization temperature of 121 °C and a holding time of 30 min and repeat the readings taken in E.2.3.4 three times.
E.2.3.7 Compare the accumulated F0 values for each reading taken from the sterilizers recorder with those taken from the test instrument and check for conformance with the recommended acceptance criteria specified in E.5.
- Method for determining the accuracy of the F0 value accumulation system using a thermal reference block approach.
- Introduction
- Method for determining the accuracy of the F0 value accumulation system using a thermal reference block approach.
This approach uses a programmable thermal reference block to create a specified thermal profile analogous to a load container of high thermal capacity (e.g. a 1 l bottle of water) and compares the F0 value calculated by the sterilizer’s recorder with that indicated by a test instrument as specified in Annex H.
- Apparatus
E.3.2.1 Programmable thermal calibration dry block or oil bath.
E.3.2.2 Test instrument with F0 value calculation capability (see Annex H).
E.3.2.3 If the test instrument does not have F0 value calculation capability, it can have the ability to export recorded data sets in a format which can be imported into spreadsheet software so that F0 values can be calculated (see Annex H).
- Procedure
E.3.3.1 Place the sterilizer’s load temperature sensor(s) into a well of the thermal block.
E.3.3.2 Place the temperature sensor of the test instrument which is attached to the F0 value accumulation channel preferably in the same well of the thermal block.
NOTE Heat contact fluid can be added if necessary to improve thermal contact between the sensors and the heated block.
E.3.3.3 The response time of the test instrument’s temperature sensor(s) should be within +/- 2,5 % of the sterilizer’s load temperature sensor(s).
NOTE If necessary, a thermal shield can be placed over the test instrument’s temperature sensor to ensure response time equivalence to the sterilizers load temperature sensor (see E.3.3.3).
E.3.3.4 Programme the thermal block to provide a heating, holding and cooling profile approximately equivalent to that of a 1 l bottle of water exposed to an operating cycle in which a theoretical sterilization temperature of 121 °C would be used for a holding time of 15 min.
E.3.3.5 Record the F0 value shown by the sterilizer’s recorder and the test instruments recorder at the commencement of the theoretical holding time and the end of the theoretical holding time.
E.3.3.6 Repeat the procedure in E.3.3.1 to E.3.3.5, twice.
E.3.3.7 Programme a second heating profile with a sterilization temperature of 121 °C and a holding time of approximately 30 min and repeat the readings taken in E.3.3.5.
E.3.3.8 Compare the accumulated F0 values for each reading taken from the sterilizers recorder with those taken from the test instrument and check for conformance with the recommended acceptance criteria specified in E.5.
- Method for determining the accuracy of the F0 value accumulation system using a reference signal input approach
- General
- Method for determining the accuracy of the F0 value accumulation system using a reference signal input approach
This method assumes that the sterilizer’s sensors will be accurately calibrated according to the requirements of this document and therefore only tests the capability of the sterilizer’s hardware and software modules to accurately calculate F0 values.
- Procedure
E.4.2.1 Introduce an electronic signal (e.g. voltage or current) representative of an equivalent defined theoretical temperature profile and therefore accumulated F0 value representative of a 1 l bottle of water exposed to an operating cycle in which a theoretical sterilization temperature of 121 °C is used for a holding time of 15 min.
E.4.2.2 Note the F0 value indicated at the commencement and end of the theoretical holding time.
E.4.2.3 Repeat twice more.
E.4.2.4 Repeat E.4.2.1 to E.4.2.3 using an equivalent holding time of 30 min.
E.4.2.5 Repeat twice more.
E.4.2.6 Compare the accumulated F0 values for each reading taken from the sterilizers recorder with those taken from the test instrument and check for conformance with the recommended acceptance criteria specified in E.5.
- Recommended acceptance criteria
Each of the accumulated F0 values recorded by the sterilizer should be equal to those recorded by the test instrument (E.2 and E.3) or calculated theoretical values (E.4) according to the tolerances shown in Table 1.
- Calculations showing the accuracy and uncertainties associated with accumulated F0 values arising from the tolerances associated with measured temperature and time
E.6.1 The calculation of accumulated F0 values is carried out using Formula (E.1).
Accumulated F0 = Σ [(10 ((T-121,1)/10) ) x Δt] (E.1)
where
T is the measured temperature at a given point in the operating cycle;
t is the time increment in minutes (1 s = 0,016 667 min).
E.6.2 The accuracy of the accumulated F0 value will depend on the two variables used in the equation, temperature (T) and time (t). Both temperature and time variables have associated tolerances specified in this document but these tolerances will depend on whether the measurement chain is part of the instrumentation attached to the sterilizer (see 6.5) or an independent test instrument (see Annex H) used for the evaluation of the sterilizer to some of the requirements specified in this document.
E.6.3 For measurement chains attached to the sterilizer the tolerances for temperature measurement are that they should not exceed 1 % over the scale range 50 °C to 150 °C but not exceed 0,5 K at the used sterilization temperatures. It should be noted that these differential tolerances on temperature measurement accuracy create an anomaly when F0 value accumulation is carried out over a range of temperatures, typically 110 °C to 125 °C (or in some instances as low as 100 °C). Time measurement tolerances are 1 % of each defined stage of the operating cycle. For test instruments the tolerance on temperature measurement is +/- 0,25 % over the scale range 0 °C to 150 °C. Time measurement has a tolerance of +/- 1 s for any measured period of the operating cycle.
E.6.4 When an accumulated F0 value approach is taken for process control then the allowed temperature and time tolerances will have an impact on the calculated F0 values. Table 1 shows a number of target F0 values assumed to be delivered by a process operating at 121,1 °C (holding stage) and the range of F0 values which can be calculated by the automatic controller allowing for the measurement tolerances described in E.6.3.
E.6.5 Examples of the calculations used to determine the values shown in Table 1 are shown below in Table E.1.
Table E.1 — Example of the calculations used to derive the values in Table 1
Lower tolerance (T-0,5 °C, t-1 %) | Target F0 value | Upper tolerance (T+0,5 °C, t+1 %) |
For T = 120,6 °C and t = 14,85' | For T = 121,1 °C and t = 15' | For T = 121,6 °C and t = 15,15' |
|
|
|
T = temperature in °C t = time in min | ||
(normative)
Test methods and reference loads for contained product sterilizers- Background
F.1.1 Sterilizers conforming with this document can be designed to sterilize a specific load. A purchaser can develop a specification for such sterilizers which will include performance requirements, tests and acceptance criteria for a specific load configuration.
F.1.2 The basic performance of a sterilizer conforming with this document can be determined using the tests described in this annex including an empty chamber test, a test using a load of low thermal capacity and a test using a load of high thermal capacity.
NOTE 1 Such basic performance tests can be used for sterilizers supplied to a health care facility where a variety of load configurations can need to be processed.
NOTE 2 In defining a load of low and high thermal capacity this document specifies the containers which can be used, some meeting the requirements of a standard. If a container other than that specified in this document is used it shall be specified and documented and where possible conform with an international or national standard.
F.1.3 Sterilizers conforming with this document can utilise active air removal employing a chamber evacuation stage. If an active air removal stage forms part of the sterilization process, the efficacy of air removal and steam penetration can be established using the methods described in EN 285.
F.1.4 The tests described in Annex F fall into a few basic categories as follows.
F.1.4.1 Automatic control tests are designed to show that the operating cycle functions correctly as evidenced by the values of the cycle variables indicated and recorded by the instruments fitted permanently to the sterilizer.
F.1.4.2 Thermometric tests using a test instrument (see Annex H) use accurate measuring equipment to monitor temperatures and pressures independently of the instruments fitted to the sterilizer. They provide the assurance that the temperature requirements for sterilization are met.
1. Thermometric tests for a small load (see F.3) are designed for two purposes. In sterilizers with an active air removal stage they demonstrate that the sterilizer is capable of removing air from a small load in which air from a near- empty chamber has been retained. In sterilization cycles which employ water sprays as a cooling medium they demonstrate that sufficient condensate will be collected for cooling purposes, and that any initial temperature overshoot as steam enters the chamber is kept within acceptable limits.
2. Thermometric tests for a full load (see F.4) are designed to show that sterilization conditions are present in a test load of specified maximum mass and of sufficient size to fill the usable chamber space.
3. Thermometric tests for minimum (small load, F.3) and maximum (full load, F.4) loads are often used as part of a PQ study (bracketing) (see ISO 17665:2024).
F.1.4.3 Microbiological tests are designed to show that sterilization conditions are attained where thermometric methods are inadequate (i.e. in locations where a temperature sensor cannot be placed) and if expected by the regulatory authority.
NOTE Temperature measurements cannot differentiate hot air from moist heat (saturated steam) at the same temperature e.g. from within interstitial spaces or cavities, between layers of packaging or the headspace above a liquid.
F.1.4.4 Other tests, specific to certain types of sterilizers, are designed to show that the steam supply is suitable, the sterilizer does not produce noise which would create a hazard, the chamber is airtight (pressurized leak test), and safety devices are functioning correctly.
- Empty chamber tests
- General
- Empty chamber tests
The purpose of this section is to establish the thermometric profile of the usable chamber space when empty during a specified operating cycle.
Many of the tests require temperature sensors (or biological or chemical indicators) to be placed in the parts of the load known to be the most difficult to sterilize. To make this assessment, it is necessary to know the hottest and coolest points in the usable chamber space during an operating cycle and those points that are the fastest and slowest to heat up.
- Apparatus
F.2.2.1 Temperature recorder or wireless sensors / dataloggers according to Annex H with at least 12 channels.
NOTE In order to obtain data which has a lower systematic variation in temperature measurements, it can be necessary to use temperature probes with a higher thermal mass than those specified in Annex H.
F.2.2.2 Pressure recorder according to Annex H.
- Procedure
F.2.3.1 Place a temperature sensor(s) attached to the test instrument at the temperature reference measurement point(s).
NOTE The temperature sensor(s) can be conventionally wired devices (e.g. thermocouples) or free standing self-contained dataloggers which can have extended probes.
F.2.3.2.1 Position the remaining temperature sensors in a grid pattern throughout the usable chamber space such that they are located at representative positions which will allow the lowest and highest temperature within the chamber to be recorded and the slowest and fastest to heat up.
NOTE 1 Temperature sensors can be located 150 mm from the chamber wall at the rear of the chamber (top left and right, bottom left and right), front of the chamber (top left and right, bottom left and right) and along the geometric centre lines.
NOTE 2 In large industrial sterilizers it can be necessary to have more than 12 temperature probes for establishing the empty chamber temperature profile.
F.2.3.2.2 If in the case of insufficient availability of temperature sensors multiple operating cycles are run and the temperature sensors are moved to different locations within the chamber, then at least two sensors should remain in the same location for each test to act as comparison points.
F.2.3.3 Select an operating cycle in which the exposure temperature is 121 °C and the exposure period is 15 min.
NOTE The operating cycle can be a specifically named cycle or may be coded and accessed using an equipment maintenance access device.
F.2.3.4 Carry out the operating cycle and record the temperature and pressure from the attached sensors. At the end of the operating cycle, examine the measured temperatures and note the following:
a) the parts of the usable chamber space that are the fastest and the slowest to attain the sterilization temperature;
b) the parts of the usable chamber space that are the hottest and the coolest during the holding time or exposure period;
c) for sterilizers with a thermal door interlock simulator, the part of the usable chamber space that is the slowest to cool to 80 °C.
F.2.3.5 Repeat the operating cycle at least twice more.
NOTE In some industrial sized sterilizers the size of the chamber can require additional replicate tests in order to establish an accurate estimation of empty chamber temperature homogeneity.
F.2.3.6 Upon completion of the operating cycle examine the recorded data and check for conformance with the acceptance criteria.
- Acceptance criteria
F.2.4.1 The test should be considered satisfactory if the following requirements are met:
a) the requirements of the automatic control test are met;
b) the time at which all measured temperatures are above 121 °C is not less than 15 min;
c) during the exposure time:
i. the measured temperatures are within the range 121 °C to 124 °C;
ii. the indicated and recorded chamber temperatures are within 2 °C of the temperature measured in the reference measurement point;
iii. the temperature measured in each location does not fluctuate more than ±1 °C, and does not differ from that in other locations by more than 2 °C;
iv. the indicated and recorded chamber pressures are within 5 kPa (50mB) of the measured pressure;
d) at the end of the cycle, upon inspection, the temperature sensors have remained in position.
NOTE The temperature profile derived in this way is valid only for the usable chamber space in an empty chamber. The presence of a load can alter the measured values.
- Thermometric test for a small load
- Apparatus for conducting a type test
- Thermometric test for a small load
F.3.1.1 50 vials conforming with ISO 8362-1, each of 5 ml nominal capacity and containing 4 ml of water at less than 30 °C. The vials shall have suitable closures and seals conforming with ISO 8362-2 or ISO 8362-3.
F.3.1.2 Two wire baskets to contain the vials.
F.3.1.3 Test instrument as described in Annex H.
F.3.1.4 Test instrument or wireless sensors according to Annex H with at least 12 channels. At least one of the test instrument channels should be capable of calculating the F0 value at 1 s intervals.
- Procedure for conducting a type test
F.3.2.1 Place 25 vials of 5 ml nominal capacity, each containing 4 ml of water, in each of two wire baskets.
F.3.2.2 Support one basket in the upper rear half of the usable chamber space and the other in the lower front half. Use the upper and lower shelves if provided.
F.3.2.3 If the sterilizer is not designed to process vials or ampoules of this size, the smallest size and number of containers recommended in the sterilizer’s instructions for use or technical documentation should be used.
NOTE An approach using thermometric measurement for testing loads can be found in Annex J.
F.3.2.4 Where the sterilizer is to be used to process one size of container only, the test load may be a single container of this size, filled with the nominal volume of water and supported in a position known to be the slowest to attain the sterilization temperature.
F.3.2.5 Place temperature sensors into the following positions;
a) one at the reference measurement point;
b) one in each of the three vials that are slowest to attain a temperature of 121 °C during an operating cycle;
c) one in each of the three vials that are fastest to attain a temperature of 121 °C during an operating cycle;
d) one in each of the three vials that are slowest to cool to either 90 °C if plastic or 80 °C if glass (see 5.1.4);
e) one adjacent to the load probe (or load surrogate device, if fitted);
f) one in the coolest part of the cooling medium in the spray cooling system, (if fitted) that does not require equipment disassembly.
F.3.2.6 If fitted, insert the sterilizer’s load probe into a vial (or load surrogate device if fitted) identified as the slowest to attain 121 °C during the operating cycle. If a second probe is provided, insert it into a vial adjacent to the vial , (or load surrogate device if fitted) identified as the fastest to attain 121 °C during the operating cycle.
F.3.2.7 Connect a pressure sensor(s) to one of the test instruments channels and instal into the chamber.
F.3.2.8 For sterilizers fitted with a pressurised spray cooling system, a second pressure sensor should be connected to the test instrument and fitted to the spray cooling system discharge.
F.3.2.9 For sterilizers fitted with a heat exchanger and the secondary circuit is designed to operate at a higher pressure than the primary circuit, connect a third pressure sensor to the test instrument and fit to the secondary circuit so that the differential pressure between the circuits can be recorded.
F.3.2.10 Select an operating cycle which exposes the test load to a temperature of 121 °C for a holding time of 15 min.
F.3.2.11 As soon as the cycle is complete, note the temperature measured in the vials before opening the door. If the temperature of any of the vials is greater than 80 °C do not open the door.
F.3.2.12 If required, collect a sample of the coolant water for subsequent quality tests.
F.3.2.13 If the coolant water is derived from a water or steam service and is intended to come into contact with the load calculate the F0 value from the temperatures measured by the coolant water sensor (see F.3.3.5 f)) using Formula E.1 from when the coolant first reaches 110 °C during the heating period and then cools to less than 110 °C during the cooling period.
- Apparatus for conducting a works test or installation qualification tests
F.3.3.1 Six (6) vials conforming with ISO 8362-1, each of 50 ml nominal capacity and containing 40 ml of water at less than 30 °C. The vials shall have suitable closures and seals conforming with ISO 8362-2 or ISO 8362-3.
F.3.3.2 One wire basket to contain the vials.
F.3.3.3 Test instrument as described in Annex H.
F.3.3.4 Test instrument or wireless sensors according to Annex H with at least 9 channels. At least one of the test instrument channels should be capable of calculating F0 values at 1 s intervals.
NOTE The works test can also be a repeat of the type test (see F.3.1).
- Procedure for conducting a works test or installation qualification tests
F.3.4.1 Place 6 vials of 50 ml nominal capacity, each containing 40 ml of water, in one wire basket.
F.3.4.2 Support the basket in the lower front half of the chamber.
F.3.4.3 If the sterilizer is not designed to process vials or ampoules of this size, the smallest size and number of containers recommended in the sterilizer’s instructions for use or technical documentation should be used.
F.3.4.4 Where the sterilizer is to be used to process one size of container only, the test load may be a single container of this size, filled with the nominal volume of water and supported in a position known to be the slowest to attain the sterilization temperature.
NOTE An approach using thermometric measurement for testing loads can be found in Annex J.
F.3.4.5 Place temperature sensors into the following positions;
a) one at the reference measurement point;
b) one in each of the vials;
c) one adjacent to the load probe (or load surrogate device, if fitted);
d) one in the coolest part of the coolant in the spray cooling system (if fitted) that does not require equipment disassembly.
F.3.4.6 If fitted, insert the sterilizer’s load probe into a vial (or load surrogate device, if fitted) identified as the slowest to attain 121 °C during the operating cycle. If a second probe is provided, insert it into a vial adjacent to the vial identified as the fastest to attain 121 °C during the operating cycle, (or load surrogate device, if fitted).
F.3.4.7 Connect a pressure sensor(s) to one of the test instruments channels and install into the chamber.
F.3.4.8 For sterilizers fitted with a pressurised spray cooling system, a second pressure sensor should be connected to the test instrument and fitted to the spray cooling system discharge.
F.3.4.9 For sterilizers fitted with a heat exchanger and the secondary circuit is designed to operate at a higher pressure than the primary circuit, connect a third pressure sensor to the test instrument and fit to the secondary circuit so that the differential pressure between the circuits can be recorded.
F.3.4.10 Select an operating cycle which exposes the test load to a temperature of 121 °C for a holding time of 15 min.
F.3.4.11 As soon as the cycle is complete, note the temperature measured in the vials before opening the door. If the temperature of any of the vials is greater than 80 °C do not open the door.
F.3.4.12 If required, collect a sample of the coolant water for subsequent quality tests.
F.3.4.13 If the coolant water is derived from a water or steam service and is intended to come into contact with the load calculate the F0 value from the temperatures measured by the coolant water sensor (see F.3.4.5 d)) using Formula E.1 from when the coolant first reaches 110 °C during the heating period and then cools to less than 110 °C during the cooling period.
- Results
F.3.5.1 Examine the vials for integrity.
F.3.5.2 Examine the temperature records. Analyse the record of the temperatures of the cooling water, if fitted, during the cycle and identify when 110 °C was attained by the cooling water during the heating period and cooled to less than 110 °C during the cooling period. Either:
a) note the F0 value for the cooling water probe calculated by the recorder; or
b) export the temperature recording from the cooling water probe into spreadsheet software and calculate the F0 value according to Formula (E.1).
- Acceptance criteria
F.3.6.1 When the sterilizer is operated with a small load the test should be considered satisfactory if the following requirements are met:
a) the requirements of the automatic control test are met (see F.5);
b) the holding time is not less than 15 min;
c) during the holding time:
i. the measured temperatures are within the range 121 °C to 124 °C;
ii. the measured temperatures are within 2 °C of each other;
iii. the indicated and recorded chamber temperatures are within 2 °C of the temperature measured at the temperature reference measurement point;
NOTE If the sterilizer is to be used for temperature sensitive products then a greater level of thermal stability and process control can be specified in which case a smaller tolerance on the temperature differences given in ii) and iii) above can be required.
iv. the indicated and recorded chamber pressures are within 5 kPa (50 mB) of the measured pressure;
v. if the recorded chamber pressure is within 5 kPa (50 mB) of the theoretical pressure calculated from the temperature measured at the temperature reference measurement point using the steam tables shown in ISO 17665:2024, Annex E;
NOTE See also References [47] and [50].
vi. if a steam-air mixture process is in use, the chamber pressure specified in the instructions for use or technical documentation for the sterilizer.
d) throughout the operating cycle:
i. the coolant spray pressure conforms with the specification;
ii. if applicable, the pressure in the heat exchanger secondary circuit is greater than that in the primary circuit.
e) when the automatic controller indicates the operating cycle is complete:
i. the temperature sensors have remained in position;
ii. the vials containing the sensors have not leaked, burst or broken;
iii. not more than one of the other vials (or 1 %, whichever is the greater) has burst or broken;
iv. the temperature measured in the vials is not greater than 80 °C (see 5.1.4).
f) the accumulated F0 value for the temperature measured in the cooling water is greater than 15 min;
g) the cycle profile, cycle stage limits and durations are as specified in the technical documentation.
- Thermometric test for a full load
- Apparatus for conducting a type test
- Thermometric test for a full load
F.4.1.1 1 l glass bottles conforming with ISO 8536-1, in sufficient number to provide a full load as specified in the sterilizer technical documentation. The bottles shall have suitable closures and seals conforming with ISO 8362-2 or ISO 8362-3.
F.4.1.2 Test instrument as described in Annex H.
F.4.1.3 Test instrument or wireless sensors according to Annex H with at least 12 channels. At least one of the test instrument channels should be capable of calculating the F0 value at 1 s intervals.
- Procedure for conducting a type test
F.4.2.1 Place 1 l of water at less than 30 °C into each bottle. Insert a temperature sensor into each of the chosen test bottles (see F.4.3.5) so that its sensing point is at approximately 85 % of the bottle depth and along the centre lines of the bottle. Seal the bottles.
NOTE See Annex L for guidance on temperature sensor placement.
F.4.2.2 Load the chamber with the filled 1 l bottles at the minimum spacing recommended in the sterilizer’s instructions for use or technical documentation. The bottles and load carrier should fill the usable chamber space.
F.4.2.3 If the sterilizer is not designed to process 1 l bottles, the largest size and number of containers recommended in the sterilizer’s instructions for use or technical documentation should be used.
NOTE An approach using thermometric measurement for testing loads can be found in Annex J.
F.4.2.4 Where the sterilizer is to be used to process one size of container only, the test load may be a single container of this size, filled with the nominal volume of water and supported in a position known to be the slowest to attain the sterilization temperature.
F.4.2.5 Place temperature sensors into the following positions:
a) one at the reference measurement point;
b) one in each of the three bottles that are slowest to attain a temperature of 121 °C during an operating cycle;
c) one in each of the three bottles that are fastest to attain a temperature of 121 °C during an operating cycle;
d) one in each of the three bottles that are slowest to cool to either 90 °C if plastic or 80 °C if glass (see 5.1.4);
e) one adjacent to the load probe (or load surrogate device, if fitted);
f) one in the coolest part of the cooling medium in the spray cooling system, (if fitted) that does not require equipment disassembly.
F.4.2.6 If fitted, insert the sterilizer’s load probe into a bottle (or load surrogate device, if fitted) identified as the slowest to attain 121 °C during the operating cycle. If a second probe is provided, insert it into a bottle adjacent to the bottle, (or load surrogate device if fitted) identified as the fastest to attain 121 °C during the operating cycle.
F.4.2.7 Connect a pressure sensor(s) to one of the test instruments channels and instal into the chamber.
F.4.2.8 For sterilizers fitted with a pressurised spray cooling system, a second pressure sensor should be connected to the test instrument and fitted to the spray cooling system discharge.
F.4.2.9 For sterilizers fitted with a heat exchanger and the secondary circuit is designed to operate at a higher pressure than the primary circuit, connect a third pressure sensor to the test instrument and fit to the secondary circuit so that the differential pressure between the circuits can be recorded.
F.4.2.10 Select an operating cycle which exposes the test load to a temperature of 121 °C for a holding time of 15 min.
F.4.2.11 As soon as the cycle is complete, note the temperature measured in the bottles before opening the door. If any of the bottles are above 80 °C do not open the door.
F.4.2.12 If required, collect a sample of the coolant water for subsequent quality tests.
F.4.2.13 If the coolant water is derived from a water or steam service and is intended to come into contact with the load calculate the F0 value from the temperatures measured by the coolant water sensor (see F.4.3.5 f)) using Formula E.1 shown in E.6.1 from when the coolant first reaches 110 °C during the heating period and then cools to less than 110 °C during the cooling period.
- Apparatus for conducting a works test or installation qualification tests
F.4.3.1 Eight (8) 1L bottles conforming to ISO 8536-1. The bottles shall have suitable closures and seals conforming with ISO 8362-2 or ISO 8362-3.
F.4.3.2 Test instrument as described in Annex H.
F.4.3.3 Test instrument or wireless sensors according to Annex H with at least 11 channels. At least one of the test instrument channels should be capable of calculating the F0 value at 1 s intervals.
NOTE The Works Test can also be a repeat of the Type Test (see F.4.1).
- Procedure for conducting a works test or installation qualification tests
F.4.4.1 Place 1L of water at less than 30 °C into each bottle. Insert a temperature sensor into each of the test bottles (see F.4.4.4) so that its sensing point is at approximately 85 % of the bottle depth and along the approximate centre line of the bottle. Seal the bottles.
NOTE See Annex L for guidance on temperature sensor placement.
F.4.4.2 If the sterilizer is not designed to process bottles of this size, the smallest size and number of containers recommended in the sterilizer’s instructions for use or technical documentation should be used.
F.4.4.3 Where the sterilizer is to be used to process one size of container only, the test load may be a single container of this size, filled with the nominal volume of water and supported in a position known to be the slowest to attain the sterilization temperature.
NOTE An approach using thermometric measurement for testing loads can be found in Annex J.
F.4.4.4 Place temperature sensors into the following positions:
a) one at the reference measurement point;
b) one in each of the bottles;
c) one adjacent to the load probe (or load surrogate device, if fitted);
d) one in the coolest part of the coolant in the spray cooling system, (if fitted) that does not require equipment disassembly.
F.4.4.5 If fitted, insert the sterilizer’s load probe into a bottle (or load surrogate device, if fitted) identified as the slowest to attain 121 °C during the operating cycle. If a second probe is provided, insert it into a container adjacent to the container identified as the fastest to attain 121 °C during the operating cycle, (or load surrogate device if fitted).
F.4.4.6 Connect a pressure sensor(s) to one of the test instruments channels and install into the chamber.
F.4.4.7 For sterilizers fitted with a pressurised spray cooling system, a second pressure sensor should be connected to the test instrument and fitted to the spray cooling system discharge.
F.4.4.8 For sterilizers fitted with a heat exchanger and the secondary circuit is designed to operate at a higher pressure than the primary circuit, connect a third pressure sensor to the test instrument and fit to the secondary circuit so that the differential pressure between the circuits can be recorded.
F.4.4.9 Select an operating cycle which exposes the test load to a temperature of 121 °C for a holding time of 15 min.
F.4.4.10 As soon as the cycle is complete, note the temperature measured in the vials before opening the door. If any of the containers are above 80 °C do not open the door.
F.4.4.11 If required, collect a sample of the coolant water for subsequent quality tests.
F.4.4.12 If the coolant water is derived from a water or steam service and is intended to come into contact with the load containers calculate the F0 value from the temperatures measured by the coolant water sensor (see F.3.4.5 d)) using Formula E.1 shown in E.6.1 from when the coolant first reaches 110 °C during the heating period and then cools to less than 110 °C during the cooling period.
- Results
F.4.5.1 Examine the bottles for integrity.
F.4.5.2 Examine the temperature records. Analyse the record of the temperatures of the cooling water, if fitted, during the cycle and identify when 110 °C was attained by the cooling water during the heating period and cooled to less than 110 °C during the cooling period.
Either:
a) note the F0 value for the cooling water probe calculated by the recorder; or
b) export the temperature recording from the cooling water probe into spreadsheet software and calculate the F0 value according to Formula (E.1).
- Acceptance criteria
F.4.6.1 When the sterilizer is operated with a full load the test should be considered satisfactory if the following requirements are met:
a) the requirements of the automatic control test are met (see F.5);
b) the holding time is not less than 15 min;
c) during the holding time:
i. the measured temperatures are within the range 121 °C to 124 °C;
ii. the measured temperatures are within 2 °C of each other;
iii. the indicated and recorded chamber temperatures are within 2 °C of the temperature measured at the temperature reference measurement point;
NOTE If the sterilizer is to be used for temperature sensitive products then a greater level of thermal stability and process control can be specified in which case a smaller tolerance on the temperature differences given in ii and iii above can be required.
iv. the indicated and recorded chamber pressures are within 5 kPa (50 mB) of the measured pressure;
v. if the recorded chamber pressure is within 5 kPa (50 mB) of the theoretical pressure calculated from the temperature measured at the temperature reference measurement point using the steam tables shown in ISO 17665:2024, Annex E;
vi. if a steam-air mixture process is in use, the chamber pressure specified in the instructions for use or technical documentation for the sterilizer.
d) throughout the operating cycle:
i. the coolant spray pressure conforms with the specification;
ii. if applicable, the pressure in the heat exchanger secondary circuit is greater than that in the primary circuit.
e) when the automatic controller indicates the operating cycle is complete:
i. the temperature sensors have remained in position;
ii. the containers containing the sensors have not leaked, burst or broken;
iii. not more than one of the other containers (or 1 %, whichever is the greater) has burst or broken;
iv. the temperature measured in the container(s) is not greater than 80 °C (see 5.1.4).
f) the accumulated F0 value for the temperature measured in the cooling water is greater than 15 min;
g) the cycle profile, cycle stage limits and durations are as specified in the technical documentation.
- F.5 Automatic control test
- General
- F.5 Automatic control test
The automatic control test is designed to show that the operating cycle functions correctly as evidenced by the values of the cycle variables indicated and recorded by the instruments fitted to the sterilizer. It is carried out as the main test for ensuring that the sterilizer continues to function correctly.
- Apparatus
During the commissioning, periodic test programs, the temperature and pressure sensors for subsequent thermometric tests will be connected to the chamber during this test. If one sensor is placed in the reference measurement point the calibration of the sterilizer instruments may conveniently be checked during the holding time of the automatic control test.
- Procedure
F.5.3.1 Select the cycle to be tested.
F.5.3.2 For commissioning tests, leave the chamber empty except for the chamber furniture.
F.5.3.3 For sterilizers with load probes insert the probes into the location specified by the manufacturer.
F.5.3.4 Ensure that a batch process record is made by the recording instrument fitted to the sterilizer.
F.5.3.5 As soon as the cycle is complete, but before opening the door, observe and note the recorded temperature in the containers which should be below 90 °C (plastic containers) or 80 °C (glass).
NOTE For temperatures upon cycle completion see also 5.1.4.
- Acceptance criteria
F.5.4.1 The following acceptance criteria shall be met.
a) A visual display of cycle complete is indicated.
b) During the whole of the cycle the values of the cycle variables shown on the batch process record are within the limits established in the process specification as giving satisfactory results.
c) During the plateau period determined from the recorded chamber temperature:
1. the indicated and recorded chamber temperatures are within the appropriate sterilization temperature band specified in the process specification;
2. the difference between the indicated and recorded chamber temperature does not exceed 2 °C;
3. the difference between the indicated and recorded chamber pressure does not exceed 10 kPa (100 mB);
4. the holding time determined from any load temperature probes is not less than that specified for the operating cycle.
d) During the holding time, any temperatures recorded in the load are within the appropriate sterilization temperature band for the operating cycle.
e) At the end of the cycle the temperature recorded in the containers is not greater than 90 °C (plastic) or 80 °C (glass).
NOTE For temperatures upon cycle completion see also 5.1.4.
f) No fault or failure is observed or any mechanical or unexpected anomaly observed.
- Chamber leakage test at super atmospheric pressures
- General
- Chamber leakage test at super atmospheric pressures
The chamber leakage test at super atmospheric pressures is used to demonstrate that the quantity of air leakage from the sterilizer chamber during the periods when it is above atmospheric pressure does not exceed a level that will cause a hazardous situation or impede the efficacy of the sterilization cycle.
- Apparatus
F.6.2.1 Pressure instruments as described in Annex H.
F.6.2.2 Stopwatch, with a maximum permissible measurement error of not more than ±0,5 s over a period of 15 min.
F.6.2.3 Connected services.
- Procedure
F.6.3.1 Close and seal the chamber and pressurise with compressed air to the MPWP.
F.6.3.2 Stabilize the temperature and pressure of the chamber.
NOTE As an example, in a closed vessel the pressure rises as the temperature rises and therefore masks any leaks. The test can be compromised if the temperature changes by more than 2 K during the period in which the sterilizer chamber pressure is monitored.
F.6.3.3 With the temperature stabilized and the sterilizer chamber empty except for fixed furniture and necessary sensors observe and record the time (t1) and the pressure (p1). Wait at least 300 s and not more than 600 s to allow stabilisation of pressure within the chamber and then observe and record the pressure (p2) in the chamber and the time (t2). After a further (600 ± 10) s, again observe and record the pressure (p3) and the time (t3).
NOTE This procedure can be carried out automatically by the automatic controller.
F.6.3.4 At the end of the test calculate the rate of pressure decrease (p2-p3) for the 600 s period and check for conformance with the sterilizer specification (a suggested pressure fall rate in x kPa/min).
F.6.3.5 When the sterilizer is tested as described in F.6 the rate of pressure decrease shall be within the specified limits for the sterilizer and in any case shall be not greater than x kPa/min (x mbar/min).
- Microbiological performance assessment
- General
- Microbiological performance assessment
The purpose of microbiological performance assessment is to ensure that a sterilization cycle programmed into the automatic controller is capable of delivering a process which will inactivate biological indicators of specified resistance contained within a reference load(s). This section describes microbiological performance assessment methods, based on those described in ISO 17665:2024, B.4.6 which can be used along with suitable reference loads.
NOTE Many regulatory authorities and users standard operating procedures require microbiological performance qualification. Validation of sterilization cycles used to process production loads is described in ISO 17665.
- Procedure
F.7.2.1 Determine the position(s) within the reference load where it is most difficult to achieve sterilizing conditions (see 10.4).
F.7.2.2 A biological indicator in accordance with ISO 11138-3, containing spores of Geobacillus stearothermophilus with a D121 value of not less than 1,5 min and a population of not less than 1 x 10 5 shall be used (FBIO = 7,5). The Kill Time for the biological indicator shall be not less than 13,5 min and not more than 15 min.
NOTE 1 The Kill Time is determined by multiplying the D121 value by the log10 of the population plus 4 i.e. Kill Time = D121 x (logP +4). See ISO 11138-1.
NOTE 2 The biological indicator can comprise a suspension of spores in a specified liquid contained in hermetically sealed ampoules.
NOTE 3 Biological indicators from a commercial source can be used.
F.7.2.3 Create a challenge to the sterilization cycle by placing a biological indicator into each of ten containers comprising the reference load by one of the following approaches:
a) placing biological indicators in hermetically sealed ampoules within reference load containers at position(s) where sterilizing conditions is most difficult to achieve;
b) inoculating with reference microorganisms the position(s) within reference load containers where sterilizing conditions is most difficult to achieve.
NOTE Option a) is more convenient in a sterilizer manufacturing facility where type testing, works tested and factory acceptance testing is being carried out. Option b) is more commonly used during performance qualification of product load configurations and requires a microbiological laboratory with suitably trained staff.
F.7.2.4 If the load containers contain a biological indicator according to
a) F.7.2.3 a): place a temperature sensor connected to a recorder in the same container.
NOTE The temperature probe can be used to anchor the biological indicator close to the measurement point. Some temperature probes can have specifically designed holders for this purpose.
b) F.7.2.3 b): place a temperature sensor connected to a recorder in a separate container which is then placed immediately adjacent to that containing the biological indicator according to F.7.2.5.
F.7.2.5 Place the containers within the load at previously identified positions (see 10.4.2.1).
F.7.2.6 The reference load shall be exposed to an operating cycle in which the sterilization temperature is 121 °C, the sterilization temperature band -0/+3 °C and the holding time 15 min. The operating cycle controls shall be adjusted so that they deliver a cycle which just falls within the minimum specified requirements.
F.7.2.7 Upon completion of the operating cycle the load shall be removed from the sterilizer and the biological indicators recovered and incubated according to their instructions for use.
F.7.2.8 Repeat exposure of fresh challenges to the level of treatment identified in 10.4.2.5 on at least two further occasions.
NOTE The same reference load containers can be used provided they have equilibrated to the same starting conditions as when first used (see 10.4.2.5).
- Acceptance criteria
Examination of the recorded temperature profile(s) for each of the operating cycles employed shall indicate:
a) the starting temperature of each of the monitored containers in each of the replicate load configurations was within +/- 5 °C of each other;
b) the reference measurement point temperature and each of the containers within the reference load had reached the sterilization temperature (121 °C) and was within the sterilization temperature band (-0/+3 °C) and that the holding time was not less than 15 min;
c) no faults were indicated by the automatic controller;
d) no failures were indicated by the automatic controller or observed;
NOTE A failure which is known not to affect the performance of the operating cycle is permissible. If a failure is observed which is known not to affect the performance of the operating cycle then this can be disregarded with respect to the acceptance criteria. For example a low water alarm for the vacuum pump occurring at the end of the operating cycle.
e) all monitored containers were below 80 °C when cycle complete was indicated;
f) none of the biological indicators showed growth after incubation according to the instructions for use.
- Chamber leakage test at sub atmospheric pressures
- General
- Chamber leakage test at sub atmospheric pressures
F.8.1.1 The air leakage test is used to demonstrate that the quantity of air leakage into the sterilizer chamber during the periods of vacuum does not exceed a level that will inhibit the penetration of steam into the sterilizer load and will not be a potential cause of re-contamination of the sterilizer load during drying.
- Apparatus
F.8.2.1 Pressure instruments as described in Annex H.
NOTE If the sterilizer is fitted with an absolute pressure instrument conforming with Annex H this additional instrument is not required.
F.8.2.2 Stopwatch, with a maximum permissible measurement error of not more than ±0,5 s over a period of 15 min.
F.8.2.3 All services required to conduct an operating cycle.
- Procedure
F.8.3.1 Connect the pressure instruments to the sterilizer chamber.
F.8.3.2 Stabilize the temperature of the sterilizer chamber by carrying out one of the following:
a) if the pressure vessel incorporates a heated jacket, carry out an operating cycle with the chamber empty;
b) if the pressure vessel does not incorporate a heated jacket, ensure that the temperature of the sterilizer chamber is not more than 20 K from ambient.
NOTE As an example, in a closed vessel at 4 kPa pressure, the pressure changes by approximately 0,1 kPa for each 10 K change in temperature, over the range 20 °C to 140 °C; at 7 kPa the change is approximately 0,2 kPa. The test can be compromised if the temperature changes by more than 10 K during the period in which the sterilizer chamber pressure is monitored.
F.8.3.3 With the temperature stabilized and the chamber empty except for fixed fittings and necessary sensors, start the test cycle. When the absolute pressure in the sterilizer chamber is 7 kPa or below close all the valves connected to the sterilizer chamber and stop the vacuum pump. Observe and record the time (t1) and the pressure (p1). Wait at least 300 s and not more than 600 s to allow evaporation of condensate in the sterilizer chamber and then observe and record the pressure (p2) in the sterilizer chamber and the time (t2). After a further (600 ± 10) s, again observe and record the pressure (p3) and the time (t3).
NOTE This procedure can be carried out automatically using a pre-programed leak rate operating cycle.
F.8.3.4 At the end of the test calculate the rate of pressure rise for the 600 s period and check for conformance with the specified acceptance criteria.
NOTE 1 A value of not more than 0,13 kPa/min has been found to be satisfactory.
NOTE 2 If the value of (p2 - p1) is greater than 2 kPa, this can be due to the initial presence of excessive condensate in the sterilizer chamber.
(informative)
Suggestions for information which can be supplied by the purchaser of the sterilizer
G.1 This annex contains points of information which may be useful in forming an agreement or useful information which may assist in establishing a suitable location for and installation of the sterilizer meeting the specifications given in 11.2 through 11.6.
G.2 The purchaser may make the following information known:
a) any statutory or other regulations with which the sterilizer is required to comply;
NOTE 1 Such a list can be non-inclusive of all requirements, especially some specific national regulations can apply if different from international regulations.
b) the name of each regulatory authority referred to in item a);
c) the type of goods to be sterilized;
d) the maximum load dimensions for each operating cycle including the sizes of the largest and of the smallest container and the loading configurations likely to be processed;
e) the required shape and size of the sterilizer;
f) the required materials of construction;
g) the sterilization process monitoring strategy and expected and types and numbers of operating cycles including, information such as the preheating capabilities, the critical stages, process parameter and cycle parameter ranges, and the nature of any alarms signalling cycle complete or a fault or failure, which will be carried out during the useful life of the sterilizer;
h) the location of any emergency stop buttons or switches;
NOTE 2 This can be governed by regulatory requirements. Specific regulatory requirements can apply regarding the location of the emergency stop button.
i) any additional instrumentation and controls to be fitted;
j) the units of measurement for pressure and temperature instruments;
k) the type of recorder(s) to be fitted;
l) the load supporting and handling equipment required;
m) the design temperatures of the environment intended for the working areas;
NOTE 3 This can include separate design temperatures for the work area in front of enclosing facia panels and that behind them (plant / equipment maintenance area).
n) the maximum through-put in an average working day and when required, including additional clarifying information such as how many shifts per day and/or how many working days per year;
o) the mode of cooling required for stage 4 e.g. passive natural cooling or assisted cooling;
p) the nature of any over pressure protection measures (e.g. air ballasting) required for containers likely to be damaged during processing.
q) the intended temperature range(s), if any, required;
r) the number of simulators required, if more than two;
s) the size(s) of the load containers to which the temperature sensors should relate;
t) available utilities and connections information (e.g. electricity, steam, water, air, drain, ventilation, vent lines) including operating ranges / classifications / quality specifications as required (e.g. voltages, available pressure ranges, flow capacity ranges, temperature ranges, instrument air quality, steam qualities, water qualities, labelling, and regulatory references as applicable);
u) layout and dimensions of the location of the equipment including access to plans to the point of location and service access;
v) type of installation (e.g. free-standing installation, single-door/double-door equipment, door opening control strategy, mounted between walls, sealing requirements);
w) required information for installation such as concrete slab information (maximum weight allowed) for mounting the sterilizer and any adjacent/ancillary equipment within scope of delivery;
x) hauling route and required dimensions, indicating the need for split assembly/crating of equipment;
y) purchaser’s contact information;
z) the expected number, locations and types of temperature and pressure sensors including redundancies;
aa) the expected materials and dimensions of the trollies, trucks, carts, or other product conveyance systems;
bb) expected automated/manual loading/unloading systems;
cc) expected steam, water, and air sampling ports, isolation valves, and filtration systems;
dd) expected instrument pass-through penetration details;
ee) expected loading/unloading ramps;
ff) expected closed cooling water loop items: isolation valves, heat exchanger type, cooling fluid, leak off protection, differential pressure control across heat exchanger plates;
gg) expected heating and/or cooling water distribution system;
hh) expected sterilization process data capture, documentation, digital and analog requirements, electronic signature capabilities, audit trail capabilities, including conformance with local regulations; computer system backup. recovery requirements, password-protected user levels;
ii) expected manual sterilization cycle control capabilities;
jj) expected condensate and water reclamation and isolation capabilities;
kk) expected water level sensing and control;
ll) expected air conveyance system including components, monitoring, and control;
mm) documents expected to be provided.
(normative)
Test instrumentation- Test instruments
H.1.1 Alternative measuring systems (e.g. free standing data loggers) may be used as long as they fulfil the requirements of this annex.
H.1.2 If such alternative measuring systems are used the impact on measurements of characteristics such as the additional mass of the electronic housing and the heat conductivity and thermal mass of the sensor probe(s) shall be assessed.
H.1.3 If such alternative measuring systems are used the temperature compensation measures taken shall ensure measurement accuracy remains within the specification given in this annex both when the measuring system is at ambient and when at sterilizing temperatures.
NOTE Free standing dataloggers have the advantage that the integrity of the chamber need not be disrupted by the introduction of sensors and connecting cables through a port in the chamber. For real time data logging systems an antenna can need to be introduced into the chamber.
- Pressure instruments
H.2.1 A test measurement system shall be used to check the pressure indicating and recording instruments attached to the sterilizer. The system may include one or more test gauges or measuring systems incorporating transducers.
H.2.2 An absolute pressure transducer shall:
a) include the range 0 kPa to 400 kPa;
b) have a response time for rising pressure of ≤ 0,12 s.
NOTE The absolute pressure transducer includes the sensor of pressure, the signal conversion elements and transmitter (if applicable).
H.2.3 The pressure measuring chains shall:
a) indicate in kilopascals or bars;
b) include the range 0 kPa to 400 kPa;
c) indicate in absolute pressure units;
d) have a resolution not exceeding 0,1 kPa;
e) have a maximum permissible measurement error not exceeding 1 kPa;
f) if used for the air leakage test, have a scale range specified for the sterilizer and a measurement error not exceeding 0,1 kPa over any pressure difference of 1,5 kPa during the test.
NOTE In some cases it can be necessary to have a pressure measuring chain specifically for conducting the air leakage test which has a sensor of smaller range e.g. 0 to 100 kPa in order to achieve the tolerances specified in H.2.3 f).
- Temperature instruments
- Probes for testing
- Temperature instruments
H.3.1.1 Temperature probes (sensors) shall be either
a) platinum resistance thermometers conforming with Class A of IEC 60751:2022, Table 2; or
b) thermocouples conforming with one of the tables of Tolerance Class 1 of IEC 60584-1:2013, Table 1.
NOTE Other probes for testing of demonstrated equivalence can be used.
H.3.1.2 The response time of the temperature probe(s) shall be ≤ 0,5 s when tested in flowing water at a temperature of 95 °C with a velocity of 0,3 (+/- 0,1) m/ sec according to IEC 60751:2022, 6.5.2.
NOTE The method described in 6.5.6.2 NOTE can also be used to determine response time.
H.3.1.3 The cross-sectional area of any part of the probe for testing and its connecting wires within the usable space shall not exceed 3,1 mm2.
H.3.1.4 The cross-sectional area, thermal mass and response time of the probe which will be used to determine the accuracy of the sterilizer’s F0 value accumulation system using the methods described in Annex E shall be equivalent to that of the fixed load probe.
NOTE This can be achieved by placing a metal sheath of appropriate thermal characteristics over one of the test instruments probes.
H.3.1.5 The performance characteristic for the temperature probes shall not be affected by the working environment in which it is placed, e.g. pressure, steam, water, air or other over pressurising gas or vacuum.
- Temperature measuring chains
H.3.2.1 The temperature measuring chains, including temperature instruments specified in H.4.1.1 shall:
a) indicate in degrees Celsius or Fahrenheit;
b) have a scale which includes the range 0 °C to 150 °C;
c) have a resolution of 0,1 K or better;
d) have a maximum permissible measurement error of ±0,25 % over the scale range 0 °C to 150 °C;
e) have a maximum permissible measurement error not exceeding 0,2 K, if the temperature measuring chain is used for calibration or adjustment of measuring chains of the sterilizer, which are used to record and indicate temperature;
f) have temperature error compensation such that a measurement error caused by a change in the ambient temperature does not exceed 0,04 K/K.
- Recording instruments
- Thermometric recording instrument
- Recording instruments
H.4.1.1 A thermometric recording instrument(s) shall record the temperatures measured in the locations specified in the tests described in this document. It can also be used to check thermometric instruments fitted to the sterilizer.
H.4.1.2 The thermometric recording instrument(s) shall:
a) record the temperatures from a minimum of twelve temperature measuring chains, each conforming with H.3.1.2;
b) record temperatures in the range and scale specified in H.3.1.2;
c) the channels can be multiplexed or independent of each other;
d) the sampling rate for each channel shall be 1 s or less;
e) the temperature measured by all temperature measuring chains shall not differ by more than 0,5 K at the used sterilization temperatures;
f) the accuracy of time measurement for each channel shall be +/- 1 s or less for any measured time period.
NOTE When using modern instrumentation the difference between each measuring chain can be 0,2 K or less.
H.4.1.3 One or more channels of the thermometric recording instrument may be programmed to calculate F0 values by using Formula (H.1).
Accumulated F0 = Σ [(10 ((T-121,1)/10) ) x Δt)] (H.1)
where
T is the measured temperature at a given point in the operating cycle;
t is the time increment in minutes (1 s = 0,016 667 min).
Examples of calculated F0 values using Formula (H.1) are shown in Table H.1. Table H.1 is for reference purposes to illustrate the relationship between temperature and accumulated F0 values and is not intended to be used for calculation of process accumulated F0 values. It is important to use the values shown for the conversion of s to min.
Table H.1 — Reference F0 values for one-minute increments at different temperatures
T °C | F0 value | T °C | F0 value | T °C | F0 value | T °C | F0 value |
110,0 | 0,078 | 118,0 | 0,490 | 125,0 | 2,455 | 133,0 | 15,488 |
111,0 | 0,098 | 119,0 | 0,617 | 126,0 | 3,090 | 134,0 | 19,498 |
112,0 | 0,123 | 120,0 | 0,776 | 127,0 | 3,890 | 135,0 | 24,547 |
113,0 | 0,155 | 121,0 | 0,977 | 128,0 | 4,898 | 136,0 | 30,903 |
114,0 | 0,195 | 121,1 | 1,000 | 129,0 | 6,166 | 137,0 | 38,905 |
115,0 | 0,245 | 122,0 | 1,230 | 130,0 | 7,762 | 138,0 | 48,978 |
116,0 | 0,309 | 123,0 | 1,362 | 131,0 | 9,772 | 139,0 | 61,660 |
117,0 | 0,389 | 124,0 | 1,950 | 132,0 | 12,302 | 140,0 | 77,625 |
NOTE 1 Formula (H.1) can be used to calculate intermediate F0 values.
NOTE 2 At 100 °C the F0 value would be 0,007 8 min.
H.4.1.4 If the thermometric recording instrument cannot be programmed to calculate F0 values then temperature data recorded at 1 s intervals shall be exported into spreadsheet software which shall be used to calculate accumulated F0 values using Formula (H.1).
NOTE The formula which can be used in the spreadsheet cell is =(10^(([cell reference]-121,1)/10))*0,016 667 for 1 s measurement intervals.
H.4.1.5 The thermometric recording instrument shall produce a record, which shall be retrievable and also in a form, which is readable by other systems, e.g. software systems.
NOTE Access to the record can be protected by an access device.
H.4.1.6 A thermometric recording instrument producing electronic records shall be designed to ensure the integrity of the records while it exists in the recorder.
- Pressure recording instrument
H.4.2.1 A pressure recording instrument shall be used in conjunction with the measuring chains specified in H.2 to record the absolute pressure within the sterilizer chamber during an operating cycle. It can also be used to check the pressure instrument(s) fitted to the sterilizer.
H.4.2.2 The pressure recording instrument may be integrated into the temperature recording instrument as an additional channel calibrated for pressure.
The pressure recording instrument(s) shall:
a) record the absolute pressure from a pressure measuring chain, conforming with H.2;
b) record absolute pressures in the range and scale specified in H.2;
c) have a sampling rate for each channel shall of 1 s or less.
H.4.2.3 The pressure recording instrument shall produce a record, which shall be retrievable and also in a form, which is readable by other systems, e.g. software systems.
NOTE Access to the record can be protected by an access device.
H.4.2.4 A pressure recording instrument producing electronic records shall be designed to ensure the integrity of the records while it exists in the recorder.
- Calibration of the test instrument
H.5.1 Calibration of the test instrument shall be carried out according to the instructions for use. This shall include temperature and pressure and any other signal input channel which will be attached to a sensor used to carry out the tests to demonstrate conformity of a sterilizer to this document.
EXAMPLE Temperature, pressure, voltage, current, resistance.
NOTE Temperature and pressure are process and cycle variables which are measured. Other signal inputs can be chamber circulation system speed, water circulation pump speed, heated water circulation flow rate.
H.5.2 Calibration of the temperature and pressure measuring chains shall be carried out using defined procedures in a metrology facility using a working or reference standard which is traceable to the national standard or a primary standard, at the value(s) used to record the sterilization process and to assess the results of the tests, in which the measuring chain is used;
NOTE Suitable fixed points can be 50 °C, 100 °C, 115 °C, 110 °C, 121,1 °C, 125 °C, 135 °C, 140 °C and 100 kPa, 150 kPa, 200 kPa, 250 kPa, 300 kPa. If the sterilization cycle includes a vacuum stage then 5 kPa and 50 kPa can also be used.
H.5.3 When installed in the place of use, the calibration of the temperature and pressure measuring chains shall be verified with an independent temperature and pressure reference source at a temperature and pressure which falls within the sterilization temperature band or across the range of temperatures which will be used for the calculation of accumulated F0 values.
NOTE Verification of the calibration of test instruments can be carried out at the point of use. Adjustment is carried out in a controlled environment metrology laboratory using specified procedures (see H.4.1 and H.4.2).
- Validation of the accuracy of the F0 value accumulation function within the test instrument
- General
- Validation of the accuracy of the F0 value accumulation function within the test instrument
H.6.1.1 The purpose of this section is to validate the accuracy of the F0 value accumulation system within the test instrument.
H.6.1.2 The method described need only be used once unless changes are made during equipment maintenance other than calibration adjustment.
NOTE Examples of changes can be a new revision of software, a replacement multiplexer, a replacement analog to digital converted, a replacement controller circuit board, a replacement real time clock module, a replacement cold junction compensation unit.
- Apparatus
H.6.2.1 Temperature-regulated heat source, capable of being controlled at a given temperature to within 0,10 °C in the range 110 °C to 140 °C.
H.6.2.2 A working or reference temperature indicating standard which is traceable to the national standard or a primary standard.
EXAMPLE A mercury in glass thermometer, a platinum resistance thermometer.
H.6.2.3 Calibrated stopwatch accurate to +/- 1 s.
- Procedure
H.6.3.1 Install the temperature sensor(s) of the test instrument and the working reference thermometer (see H.6.2.2) into the temperature-regulated heat source.
H.6.3.2 Adjust the heat source so that it maintains at one of the temperatures shown in Table H.2 as indicated by the reference thermometer.
H.6.3.3 When the temperature of the heat source has stabilized, check that the temperature indicated by the test instrument and that by the reference thermometer are within 0,2K of each other.
H.6.3.4 Note the indicated F0 value on the test instrument or reset the value to zero and immediately start the stopwatch. Allow the test instrument to accumulate F0 values for a period as shown in Table H.2 timed with the stopwatch.
H.6.3.5 At the end of the timed period note the accumulated F0 value.
H.6.3.6 Repeat stages H.6.3.2 to H.6.3.5 twice.
H.6.3.7 Repeat steps H.6.3.2 to H.6.3.6 for the remaining temperature points shown in Table H.2.
- Acceptance criteria
H.6.4.1 Each value noted in H.6.3.5 shall be greater than the minimum accumulated F0 value and less than the maximum accumulated F0 value shown in Table H.2 for each of the test temperatures used.
Table H.2 — Test temperatures and times for the verification of the F0 value accumulation system on the test instrument and the acceptance criteria
Test temperature (H.6.3.2) +/- 0,1 °C | Test time (H.6.3.4) (+/- 1 s) min | Target accumulated F0 value a min | Minimum accumulated F0 Valueb min | Maximum accumulated F0 valuec min |
110 | 30 | 2,34 | 2,18 | 2,48 |
115 | 30 | 7,35 | 6,89 | 7,87 |
121,1 | 15 | 15,00 | 13,97 | 16,10 |
125 | 10 | 24,55 | 22,80 | 26,42 |
135 | 3 | 73,64 | 67,76 | 80,03 |
140 | 1 | 77,63 | 70,00 | 85,54 |
a The target accumulated F0 value is calculated using Formula (H.1). b The minimum accumulated F0 value is that calculated from Formula (H.1) allowing for a minus 0,25 % tolerance on temperature measurement and a -1 s tolerance on time measurement (H.3.2.1 d)). c The maximum accumulated F0 value is that calculated from Formula (H.1) allowing for a plus 0,25 % tolerance on temperature measurement and a + 1 s tolerance on time measurement (H.3.2.1 d)). | ||||
The impact of the tolerances associated with temperature measurements and accumulated F0 values should be accounted for when calculating an associated SAL calculated from accumulated F0 values particularly when using process definition based on bio-burden methods (see Annex E, particularly E.6 and ISO 17665:2024, Annex B).
(informative)
Test methods for determining steam quality- General
The steam quality measurement methods described in this annex are informative reference methods which can be used by those interested in determining the properties of steam used in their installations. Alternative instrumental methods are available which can often provide continuous read out of such properties. It is of value to know the relationship between the results from the reference methods described in this annex and any alternative methods used.
The suggested results for the steam quality properties described below are for guidance only and relate to the steam quality properties normally used for saturated steam sterilization processes used for Porous and Hard Goods or some combined products.
- Non-condensable gas
- Procedure
- Non-condensable gas
The method described in EN 285, can be used to determine the non-condensable gas level in the steam supplied to the sterilizer.
- Suggested results
The non-condensable gas level can be less than 3,5 ml of non-condensable gas in 100 ml of collected condensate.
NOTE This is often expressed as 3,5 % v/v which means 3,5 ml of non-condensable gas in 100 ml of condensed steam meaning the amount of gas in steam is approximately 2 000 times lower (see ISO 17665:2024, Annex A and E for further information).
- Dryness value
- Procedure
- Dryness value
The method described in EN 285 can be used to determine the dryness value of the steam supplied to the sterilizer.
- Suggested results
The dryness value of the steam supplied to the sterilizer can be more than 0,95 to 1,05.
- Superheat
- Procedure
- Superheat
The level of superheat can be determined using the method described in EN 285 from a sample of steam supplied to the sterilizer.
- Suggested results
The level of superheat can be less than 25 °C.
NOTE In this context the level of superheat relates to the value obtained by throttling the steam supply from the steam supply pressure to atmospheric pressure. It does not describe the level of superheat present in the sterilizer chamber when measured by temperature pressure correlation (see ISO 17665:2024, Annex E).
- Chemical and biochemical contaminants
- Procedure
- Chemical and biochemical contaminants
The method described in EN 285 can be used to collect a sample of condensate from the steam supplied to the sterilizer. The condensate sample can be subjected to chemical and biochemical analysis using standard laboratory test methods. Analytes which can be considered include but are not limited to iron, cadmium, lead, chloride, phosphate, ammonium, calcium, magnesium, nitrate sulphate and silicate ions and bacterial endotoxins. In addition, other physicochemical properties can also be considered including pH, conductivity, appearance, oxidisable substances, the residue on evaporation of a defined volume of condensate.
- Suggested results
The quantity of each chemical and biochemical contaminant can meet the recommendations shown in Clause 7.
- Pressure fluctuations
The sterilizer can be designed to operate with a steam supply which can fluctuate by +/-10 % of the specified supply pressure. The specification for the steam supply can require fluctuations not greater than +/-10 % of a nominal specified value. Pressure fluctuation can be measured at the inlet to the final pressure reduction valve.
(informative)
An exemplar thermometric approach to Performance Qualification when validating a contained product sterilization process according to ISO 17665:2024- General
The tests described in this annex can be performed to evaluate a sterilization process which employs a specific load configuration and a defined sterilization cycle employing a specified holding time at a specified sterilization temperature.
NOTE See ISO 17665:2024.
- Apparatus
The production load under test will normally consist of discrete items such as packs, bottles or other containers according to the Scope of this document.
- Procedure
J.3.1 Place temperature sensors in the following positions:
a) one in each of three items known to be the slowest to attain the sterilization temperature;
b) one in each of three items known to be the fastest to attain the sterilization temperature;
c) if the sterilizer has a thermal door interlock, one in each of three items known to be the slowest to cool to 80 °C.
NOTE In order to establish the positions listed as series of preliminary tests can be carried out.
J.3.2 If the load consists of less than six items, then place a sensor in each item.
J.3.3 The sensors should be in good thermal contact with the fluid or device which they are monitoring, and placed, if possible, in or on the part of the item slowest to heat up.
J.3.4 The fastest and slowest items should have been identified as part of the design of the load configuration. It may be desirable to confirm that the correct items have been selected by placing additional sensors in neighbouring items and running one or more preliminary operating cycles to verify that the selected items are the fastest and slowest.
J.3.5 Place a sensor either at the reference measurement point e.g. the drain or the coolest part of the chamber. (This will normally be close to the sensor connected to the sterilizer recording instrument.)
J.3.6 Insert any load temperature probes provided in the chamber into the positions they will normally occupy in the load. If a probe is required to occupy the same position as a sensor, then the sensor should be moved to a neighbouring load item if they cannot both be accommodated in the same load item.
Note the load configuration and the positions of the sensors and probes in sufficient detail for the test to be replicated on any future occasion.
J.3.7 If the sterilizer has a pressure instrument, connect a pressure recorder to the chamber.
J.3.8 Select the operating cycle that will be used for the production load. Start the cycle.
J.3.9 Ensure that a batch process record is made by the instrument fitted to the sterilizer. This will serve as the basis for a master process record for the load configuration under test. If the sterilizer does not have a recorder note the elapsed time, indicated chamber temperatures and pressures at all significant points of the operating cycle, for example the beginning and end of each stage or sub-stage as per the automatic control test (see F.6).
J.3.10 At the approximate mid-point of the plateau period, note the elapsed time and indicated chamber temperature and pressure.
J.3.11 For fluid loads, during the cooling stage wait for the temperature in the containers to fall to 90 °C (plastic containers) or 80 °C (glass). As soon as cycle complete is indicated, but before opening the door, note the recorded temperature in the containers.
NOTE For temperatures upon cycle completion see also 5.1.4.
- Acceptance criteria
J.4.1 The test should be considered satisfactory if the following requirements are met:
a) the requirements of the automatic control test are met;
b) the holding time, as determined from the measured temperatures, is not less than that specified for the appropriate sterilization temperature band;
c) during the holding time:
i. the measured temperatures are within the sterilization temperature band specified for the sterilization cycle;
ii. the indicated and recorded chamber temperatures are within 2 °C of the temperature measured in the reference measurement point;
iii. the temperature measured in each load item does not fluctuate more than ±1 °C, and does not differ from that in other load items by more than 2 °C;
iv. the indicated and recorded chamber pressures are within 5 kPa (50mB) of the measured pressure;
d) at the end of the cycle when cycle complete is indicated:
i. the temperature sensors have remained in position;
ii. the items containing sensors are intact;
iii. the temperature measured in any fluid containers is not greater than 90 °C (plastic) or 80 °C (glass).
NOTE For temperatures upon cycle completion see also 5.1.4.
J.4.2 If the test is satisfactory, it should be performed two more times to check for reproducibility and to establish permitted tolerances.
(informative)
Potential hazards associated with the sterilization of aqueous fluids in sealed rigid containers
K.1 Rigid containers for sterile fluids (i.e. glass bottles) are commonly sealed with compound closures comprising an elastomeric disc or plug which is secured to the neck of the bottle by means of an aluminium screw cap, an aluminium crimped-on (or turned-on) cap, a cap made of plastics material or a retaining closure embodying both plastics and aluminium parts.
K.2 It is essential that the elastomer is held in tight contact with the neck of the bottle in order to prevent the entry of microorganisms or other materials which can contaminate the product. It is a characteristic of such containers that when they are charged with the specified volume of the aqueous product there remains a substantial air space (sometimes referred to as ullage) above the liquid. The proportion of the total internal volume of a bottle filled with liquid may vary with the design of the bottle but is commonly 80 % to 90 %, so the ullage may be about 10 % to 20 % of the internal volume. Such a space is necessary to allow for thermal expansion of the liquid during sterilization.
K.3 When a sealed bottle is autoclaved, the pressure inside exceeds that in the sterilizer chamber by a substantial margin. The pressure within the bottle is due to the partial pressures of air and steam and dissolved gases in the liquid at the sterilizing temperature plus an additional factor due to compression of the air and steam mixture in the ullage by thermal expansion of the liquid in the bottle. Thus at any single temperature the pressure within a container under sterilizing conditions will be determined largely by the proportion of the total internal volume filled with liquid since, as this increases, the effect of thermal expansion on the air and steam mixture also increases, as illustrated in Figure K.1.
K.4 The high internal pressure within bottles during sterilization imposes a stress on the closures which may be distorted or even ruptured as a result. Distortion of closures, especially of the aluminium parts, may allow the elastomeric seal to lift or loosen in the bottle neck and allow the escape of some air from the ullage. Should this occur, the bottle, on cooling, tends to develop a partial internal vacuum.
This itself is no danger to the product but may allow the entry into the bottle of spray cooling fluid which will dilute the product and may carry in chemical or microbial contamination. An attempt is made to reduce the risk of product contamination by using retained condensate, cooling medium contained in a closed loop system and subjected to the heating and exposure stages in the sterilizer (or in some cases filtered gas) as the cooling agent. An acceptable product requires that the closure of the bottle remains an effective seal throughout the sterilization process. High pressures within bottles may cause weak or damaged containers to burst during sterilization and such explosions may damage other containers in the load. Finally, a potential hazard to the user may result if bottles are removed from the sterilizer when their temperature exceeds 80 °C. Cold draughts and/or unintentional impact may well result in explosive breakages which have been known to endanger life.
K.5 Since the above problems arise as a result of the inevitable excess pressure generated within bottles, the security of bottle closures is the responsibility of the user. Thus the user is required to ensure that the closures and containers are suitably designed to withstand the proposed sterilizing conditions. Where containers are reused, a rigid system of inspection after washing ensures that all bottles with signs of damage, especially of the neck area, are discarded.
It is imperative that a bottle is not charged with a volume of fluid greater than the stated nominal volume of the bottle.
Key
IP maximum internal pressure in bottle (bar)
V volume of water in bottle (ml). 900 ml is equal to 74 % fill volume, 1 000 ml, 82 % and 1 100 ml, 90 %
Figure K.1 — Pressure generated in a nominal 1L bottle, containing different volumes of water, when heated to 121 °C
(informative)
Methods for locating heat penetration temperature sensors into aqueous liquids in sealed containers- General
ISO 17665:2024 covers the development, validation and routine control of moist heat sterilization processes, including those for contained products. Throughout this document there are requirements for the provision of temperature sensors which can be placed within aqueous liquids in sealed containers in order to establish the heat penetration temperatures within the contained product during a sterilization cycle. Such measurements can be achieved using the temperature sensors described in 6.5.6 et seq. When temperature sensors are inserted into sealed containers for all heat penetration studies, including cold spot determination, it is essential that they are securely anchored in place to prevent any movement so as to ensure the accuracy of the results from these measurements. Failure to properly anchor temperature probes during heat penetration studies can result in inaccurate measurements of physical lethality or selection of an improper location for the cold spot. For cold spot studies, it is essential that heat penetration temperature sensors be positioned at locations within the container expected to be the slowest to heat to identify the overall cold spot that reproducibly generates the lowest level of physical lethality. The characteristics of the liquid (e.g. viscosity) can influence heat penetration.
This annex provides guidance on how temperature sensors and probes can be located in various examples of sealed containers to allow accurate measurement of heat penetration temperatures within the contained liquid.
- Temperature sensors
L.2.1 In order to conduct the tests described in this document, particularly Annex F, a number of heat penetration temperature sensors will need to be introduced into the chamber. The characteristics of the temperature sensors are given in Annex H and a method for introducing them into the chamber is described in 5.5. Introduction of temperature sensors through the door seal can cause damage and create a leak so such a method is inadvisable. After installation a leak test can be required to ensure chamber integrity (see F.6 and F.8).
Wireless dataloggers with temperature sensors which can be placed inside the chamber can be used and have the advantage of not requiring a breach in the chamber integrity that is required for hardwired sensors thereby eliminating the need for a pre and post test of chamber integrity (e.g. a leak test). If these dataloggers are used then they should meet the requirements shown in Annex H and preferably have extended flexible probes which can be introduced into the body of the contained liquid. Both wireless dataloggers which store data to be downloaded at the end of the operating cycle and those which wirelessly transmit data in real time are available.
Some temperature sensor probes are commercially available which have several sensor points located along the axis of the sheath to enable product cold spot mapping (see L.5) to be conducted by simultaneous temperature measurement at multiple locations in the container.
Irrespective of the type of heat penetration temperature sensor used, it is essential that it, or its anchoring system, does not affect the routine positioning or the heating and cooling rate of the container in the load.
Figure L.1 shows examples of support assemblies which can be used to ensure the temperature sensor remains aligned along the centre line of the container.
L.2.2 When unsheathed hardwired sensors are used (e.g. thermocouple wires), steam or fluid can be forced along the wire between the cable’s electrical insulation layers. To prevent damage to the recorder, the outer electrical insulation layers should be punctured some distance from the recorder connection point and positioned so that any emerging droplets of liquid fall clear of the recorder. Sheathed sensors are completely sealed against ingress of the heating medium or container contents so the problem associated with liquid tracking along electrical insulation cannot happen. Nevertheless, it may be expedient to take similar measures to those described above in case unnoticed damage to the sensor sheath has occurred.
L.2.3 Figure L.1 shows a number of support assemblies which allow fine gauge temperature sensors to be inserted along the centre line of a rigid, semi rigid and flexible container.
- Methods of inserting hardwired temperature sensors into containers
- Rigid containers
- Methods of inserting hardwired temperature sensors into containers
A hollow fine gauge tube is attached to a bolt with a hollow bore drilled along its centre line. The bolt is then inserted through a suitable drilling in the containers closure system, e.g. a bung, and clamped into place. The bung assembly is then inserted into the filled container and the temperature sensor pushed through the needle so as to be located at the point where temperature measurements are required. This is then sealed in place using epoxy resin or silicone sealant.
For small volume containers such as glass ampoules the temperature sensor can have sufficient rigidity to retain its position along the centre line. Epoxy resins, silicone sealants and adhesives can be used to seal the sensor in position with further support provided by autoclave tape as needed. It is essential the integrity of the ampoule containing a sensor be established before it is used for testing and in some cases, afterwards.
- Semi rigid containers
A similar system to that described in L.3.1 can be used except that a tight fitting bung is used to ensure the assembly is located along the centre line of the container.
- Flexible containers
When inserting temperature sensor probes into flexible containers it is essential to ensure that a support structure is created which ensures the sensor is and remains located within the body of the liquid during the sterilization cycle. This support structure can be internal, external or a combination of both to the container. The orientation of the container during the sterilization cycle can influence the measured heat penetration temperatures and can therefore be considered e.g. laying flat, mounted on a holder which orientates in a vertical or inverted position. Any changes in the flexibility of the container can also be considered when mounting the sensor since it may begin in a centrally located position but this then changes as the container material becomes more pliable and changes shape as a result of heating. If the contained product is sterilized in an overwrap, the temperature sensor is inserted into the required location in the contained product with seals at the penetration points into the primary overwrap and primary container.
Figure L.2 shows methods of introducing temperature sensors into rigid, semi-rigid and flexible containers of different sizes.
- Syringes
When inserting temperature probes into syringes the most convenient approach is to insert the sensor through the hole in the luer lock assembly at the end of the syringe body. A fine gauge temperature sensor which can be inserted through the fine access hole in the luer lock assembly can be used. A compression adapter can be employed which seals the fine gauge temperature sensor into place and this can be secured onto the luer lock assembly at the end of the syringe. Figure L.3 shows a picture of a syringe with a temperature sensor inserted through the luer lock assembly and sealed in place with a compression adapter.
Key
A temperature sensor
B hollow rigid narrow gauge tube
C silicone tube to seal the tube (B)
D container closure system, e.g. bung
E bolt with central hollow drilling to allow insertion of temperature sensor (A)
F silicone or semi rigid tube for insertion into semi-rigid containers e.g. polypropylene bottles
Figure L.1 — Support systems for enabling insertion of temperature sensors into rigid, semi-rigid and flexible containers
Key
A rigid glass containers, e.g. DIN containers
B rigid glass ampoules. The temperature sensor can be sealed into position using epoxy resin, silicone sealant or other suitable adhesive, further supported by autoclave tape.
C narrow necked semi-rigid polypropylene containers
D top view of a flexible container lying flat on a shelf showing the additional support wire framework assembly (a) required to ensure the temperature sensor remains within the bulk of the contained product
Figure L.2 — Methods for inserting temperature sensors into rigid, semi-rigid or flexible containers filled with aqueous liquids
Figure L.3 — Method for inserting a fine gauge temperature sensor into a syringe. The adapter creating the temperature sensor seal is attached to the luer lock assembly at the end of the syringe
- Methods of inserting wireless datalogger temperature sensors into containers
L.4.1 Wireless dataloggers can be used to measure heat penetration into the contents of rigid, semi-rigid and flexible containers and syringes.
L.4.2 Figure L.4 shows an example of how a wireless datalogger can be inserted into a rigid container. The depth of the probe can be adjusted by use of a spacer between the body of the datalogger and the cap of the container.
Figure L.4 — Method for using a wireless datalogger to measure heat penetration temperatures in a rigid container
L.4.3 Semi rigid containers
Figure L.5 shows an example of how a wireless datalogger can be inserted into a semi-rigid container. The depth of insertion of the probe can be adjusted by use of a spacer between the body of the datalogger and the entry point into the container or by adjustment of the length of penetration using the clamping mechanism.
Figure L.5 — Method for using a wireless datalogger to measure heat penetration temperatures in a semi-rigid container
L.4.4 Flexible containers
Figure L.6 shows an example of a flexible container with a wireless datalogger mounted internally and secured in position by use of a frame assembly. The datalogger can be mounted externally to the container or internally. The position of the probe can be adjusted by pushing the probe further into the contents through the filling port if mounted externally or by use of dataloggers having different probe lengths if mounted internally.
Figure L.6 — Method for using a wireless datalogger to measure heat penetration temperatures in a flexible container
L.4.5 Syringes
Figure L.7 Shows an example of a syringe with a wireless datalogger mounted at the end. The datalogger probe can be introduced through the plunger of the syringe once the plunger stem has been removed. The luer lock can then be sealed using an appropriate cap.
Figure L.7 — Method for introducing the probe of a wireless datalogger into a prefilled syringe
- Cold spot mapping
The cold spot is considered to be the location which reproducibly receives the lowest process lethality in terms of the lowest accumulated F0 value or shortest time, or the lowest measured temperature, or both, during the sterilization cycle. There are three definable cold spots in a contained product sterilization process.
1. The product cold spot is that location within a sealed container which receives the lowest process lethality.
2. The load cold spot is the location within the load which receives the lowest process lethality.
3. The chamber cold spot is the location within the chamber (either empty or loaded) which receives the lowest process lethality.
It is common to use the established product cold spot for thermal validation studies during process development and performance qualification since it is assumed that if a satisfactory sterility assurance level is achieved at this point in the container then a satisfactory sterility assurance level will be achieved at locations which are at a higher temperature and or for a longer period. The temperature can differ at various points within the container and care should be taken to establish heat penetration from different points within the container thereby enabling the product cold spot to be identified. Cold spot mapping will be established during process development and validation which is covered in ISO 17665.
Heat penetration temperature mapping to establish a product Cold Spot is usually not required for small volume containers (i.e. less than or equal to 100 ml) since these will heat up rapidly and evenly. However larger containers may exhibit thermal gradients along the vertical axis within the contained product during processing and it is therefore important to establish the product Cold Spot during process development. The larger the container the more likely thermal gradients will be observed.
In order to establish the thermal profile from multiple locations within a container several temperature sensors or a single temperature sensor with multiple sensing points can be introduced through the closure system into the contents of the container at different levels along the vertical axis and at different positions within the container. Alternatively, temperature sensors can be inserted and sealed in position at various points along the body of the container. The choice of temperature sensors of suitable physical size and response time will enable-accurate determination of thermal penetration without affecting the characteristics of the container and its contents
Sterilizer designs which enable mixing of container contents by shaking or rotation can lead to greater thermal homogeneity in container contents
Changes in the rigidity of large volume flexible containers can be taken into account when determining the location of temperature sensors for Cold Spot mapping determinations. For example, a flexible pouch hung on a load carrier can become sufficiently flexible during the sterilization cycle to allow the contents to accumulate in the lower parts creating a greater challenge to heat penetration. Similar containers placed in a horizontal orientation on the load carrier can retain their shape.
Figure L.8 shows an example of how hardwired temperature sensors can be introduced into a flexible container through the filling port and distributed at different locations within the contents.
Figure L.8 — Method for introducing multiple hardwired sensors into a flexible container for establishing the product cold spot
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