Microsoft Word C043187e doc Reference number ISO 17665 1 2006(E) © ISO 2006 INTERNATIONAL STANDARD ISO 17665 1 First edition 2006 08 15 Sterilization of health care products — Moist heat — Part 1 Requ[.]
Inclusions
1.1.1 This part of ISO 17665 specifies requirements for the development, validation and routine control of a moist heat sterilization process for medical devices
NOTE Although the scope of this part of ISO 17665 is limited to medical devices, it specifies requirements and provides guidance that may be applicable to other health care products
Moist heat sterilization processes outlined in ISO 17665 encompass various methods, including saturated steam venting systems, active air removal systems utilizing saturated steam, air-steam mixtures, water spray techniques, and water immersion methods.
Exclusions
ISO 17665 does not outline the requirements for the development, validation, and routine control of processes aimed at inactivating spongiform encephalopathy agents, including scrapie, bovine spongiform encephalopathy, and Creutzfeldt-Jakob disease However, specific recommendations for handling materials that may be contaminated with these agents have been established in various countries.
NOTE See also ISO 22442-1, ISO 22442-2 and ISO 22442-3
1.2.2 This part of ISO 17665 does not apply to those sterilization processes that are based on a combination of moist heat with other biocidal agents (e.g formaldehyde) as the sterilizing agent
1.2.3 This part of ISO 17665 does not detail a specified requirement for designating a medical device as
NOTE Attention is drawn to national or regional requirements for designating medical devices as “sterile.” See, for example, EN 556-1 or ANSI/AAMI ST67
1.2.4 This part of ISO 17665 does not specify a quality management system for the control of all stages of production of medical devices
ISO 17665 does not mandate a complete quality management system during manufacturing; however, it references essential elements necessary for controlling the sterilization process, particularly in Clause 4 It is important to note that ISO 13485 outlines standards for quality management systems that govern all production stages of medical devices, including sterilization Additionally, regional and national regulations may necessitate the implementation of a comprehensive quality management system, which could require third-party assessment.
1.2.5 This part of ISO 17665 does not specify requirements for occupational safety associated with the design and operation of moist heat sterilization facilities
NOTE Requirements for operational safety are specified in IEC 61010-2-040 Additionally, safety regulations exist in some countries
The referenced documents are essential for applying this document For dated references, only the specified edition is applicable, while for undated references, the most recent edition, including any amendments, is relevant.
ISO 10012, Measurement management systems — Requirements for measurement processes and measuring equipment
ISO 11138-1, Sterilization of health care products — Biological indicators — Part 1: General Requirements
ISO 11138-3, Sterilization of health care products — Biological indicators — Part 3: Biological indicators for moist heat sterilization processes
ISO 11140-1, Sterilization of health care products — Chemical indicators — Part 1: General requirements
ISO 11140-3, Sterilization of health care products — Chemical indicators — Part 3: Class 2 indicator systems for use in the Bowie and Dick steam penetration test
ISO 11140-4, Sterilization of health care products — Chemical indicators — Part 4: Class 2 indicators as an alternative to Bowie and Dick test for detection of steam penetration
ISO 11140-5, Sterilization of health care products — Chemical indicators — Part 5: Class 2 indicators for
Bowie and Dick air removal test sheets and packs
ISO 11607-1, Packaging for terminally sterilized medical devices — Part 1: Requirements for materials, sterile barrier systems and packaging systems
ISO 11607-2, Packaging for terminally sterilized medical devices — Part 2: Validation requirements for forming, sealing and assembly processes
ISO 11737-1, Sterilization of medical devices — Microbiological methods — Part 1: Determination of a population of microorganisms on products
ISO 11737-2, Sterilization of medical devices — Microbiological methods — Part 2: Tests of sterility performed in the validation of a sterilization process
ISO 13485:2003, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 17664, Sterilization of medical devices — Information to be provided by the manufacturer for the processing of resterilizable medical devices
For the purposes of this document, the following terms and definitions apply
3.1 air detector device designed to detect the presence of non-condensable gases in a stream of steam and condensate or in the sterilizer chamber
〈sterilization〉 device that, in response to pre-determined operating cycle variables, operates the sterilizer sequentially through the required stages of the operating cycle(s)
3.3 bioburden population of viable microorganisms on and/or in a product and/or sterile barrier system
3.4 biological indicator test system containing viable microorganisms providing a defined resistance to a specified sterilization process
Calibration is a set of operations that defines the relationship between the values indicated by a measuring instrument or system and the corresponding values established by standards, under specified conditions This process ensures accuracy and reliability in measurements by comparing them to material measures or reference materials.
3.6 chemical indicator non-biological indicator test system that reveals change in one or more pre-defined process variables based on a chemical or physical change resulting from exposure to a process
3.7 contained product product for which the environment within the sterilizer during any stage of the sterilization process does not come into direct contact with the product
NOTE The environment within the sterilizer is used for heating and cooling purposes only, not for achieving the sterilization effect; e.g a solution in a sealed bottle
3.8 correction action to eliminate a detected nonconformity
NOTE A correction can be made in conjunction with a corrective action
3.9 corrective action action to eliminate the cause of a detected nonconformity or other undesirable situation
NOTE 1 There can be more than one cause for a nonconformity
NOTE 2 Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent occurrence
NOTE 3 There is a distinction between correction and corrective action
D 10 value time or dose required to achieve inactivation of 90 % of a population of the test microorganism under stated conditions
NOTE For the purposes of this part of ISO 17665 D-value refers to the exposure necessary to achieve 90 % reduction
3.11 development act of elaborating a specification
3.12 environmental control application of engineering and/or procedural systems to maintain conditions in defined areas within specified limits
NOTE Such systems can include air and fluid filters, surface disinfection, protective clothing and administrative procedures
The equilibration time is the duration required for the sterilization temperature to be reached at all points within the sterilization load after it has been attained at the reference measuring point.
3.14 establish determine by theoretical evaluation and confirm by experimentation
3.15 exposure time period for which the process parameters are maintained within their specified tolerances
3.16 fault one or more of the process parameters lying outside its/their specified tolerance(s)
F 0 value microbiological lethality of a 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
3.18 health care product(s) medical device(s) including in vitro diagnostic medical device(s) or medicinal product(s) including biopharmaceutical(s)
〈sterilization〉 period for which the temperatures at the reference measurement point and at all points within the sterilization load are continuously within the sterilization temperature band
IQ process of obtaining and documenting evidence that equipment has been provided and installed in accordance with its specification
3.21 load configuration specified configuration within the sterilization chamber of the items of fixed chamber parts and the numbers, types, distribution and orientation of product presented for sterilization
〈sterilization〉 combination of all technical and associated administrative actions intended to retain an item at/or restore it to a state in which it can perform its required function
A medical device encompasses a range of items including instruments, apparatuses, machines, appliances, implants, in vitro reagents, calibrators, software, and other related materials These devices are specifically designed by manufacturers for use, either individually or in combination, to serve one or more defined purposes for human beings.
⎯ diagnosis, prevention, monitoring, treatment or alleviation of disease;
⎯ diagnosis, monitoring, treatment, alleviation of or compensation for an injury;
⎯ investigation, replacement, modification or support of the anatomy or of a physiological process;
In vitro examination of human-derived specimens provides essential information for medical purposes This process does not primarily achieve its intended action through pharmacological, immunological, or metabolic means, although it may be supported by these methods.
NOTE This definition from ISO 13485:2003 was developed by the Global Harmonization Task Force (GHTF 2002)
A measuring chain is a series of components within a measuring instrument or system that facilitates the transmission of the measurement signal from the input, which is the quantity being measured, to the output, which represents the measurement result.
3.25 microorganism entity of microscopic size, encompassing bacteria, fungi, protozoa and viruses
Certain standards may not necessitate proving the sterilization process's effectiveness against all microorganisms defined previously for validation or routine control.
3.26 moist heat thermal energy in the presence of moisture provided as steam or liquid water for the purpose of achieving microbial lethality
3.27 non-condensable gas air and/or other gas which will not liquefy under the conditions of a saturated steam processes
OQ process of obtaining and documenting evidence that installed equipment operates within predetermined limits when used in accordance with its operational procedures
3.29 operating cycle complete set of stages of the process, carried out in a specified sequence
3.30 packaging system combination of the sterile barrier system and protective packaging
The PQ process involves obtaining and documenting evidence that the equipment, when installed and operated according to established procedures, consistently meets predetermined performance criteria, ensuring that the resulting product adheres to its specifications.
3.32 preventive action action to eliminate the cause of a potential nonconformity or other undesirable potential situation
NOTE 1 There can be more than one cause for a potential nonconformity
NOTE 2 Preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence
3.33 plateau period equilibration time plus the holding time
PCD item designed to constitute a defined resistance to a sterilization process and used to assess performance of the process
3.35 process parameter specified value for a process variable
NOTE The specification for a sterilization process includes the process parameters and their tolerances
3.36 process variable condition within a sterilization process, changes in which alter microbicidal effectiveness
EXAMPLE Time, temperature, pressure, concentration, humidity, wavelength
NOTE For the purposes of sterilization standards, product is tangible and can be raw material(s) intermediates, sub- assembly(ies) and healthcare product(s)
〈sterilization〉 groups or subgroups of product characterized by similar attributes such as mass, material, construction, shapes, lumens, packaging system and which present a similar challenge to the sterilization process
3.39 reference challenge device device having a known thermal relationship to the contained product or sterilization load
3.40 reference load specified sterilization load(s) created to represent difficult combinations of items to be sterilized
3.41 reference measuring point point where the temperature sensor used for the operating cycle control is located
3.42 reference microorganism microbial strain obtained from a recognized culture collection
3.43 requalification repetition of part of validation for the purpose of confirming the continued acceptability of a specified process
3.44 saturated steam water vapour in a state of equilibrium between condensation and evaporation
3.45 services supplies from an external source, needed for the function of equipment
EXAMPLE Electricity, water, compressed air, drainage
3.47 specify stipulate in detail within an approved document
3.48 sterile free from viable microorganisms
3.49 sterility state of being free from viable microorganisms
NOTE In practice, no such absolute statement regarding the absence of microorganisms can be proven
SAL probability of a single viable microorganism occurring on an item after sterilization
The term Sterility Assurance Level (SAL) is quantified, typically as 10^{-6} or 10^{-3} An SAL of 10^{-6} offers a higher assurance of sterility compared to an SAL of 10^{-3}, despite its lower numerical value.
3.51 sterilization validated process used to render product free from viable microorganisms
In a sterilization process, microbial inactivation follows an exponential pattern, meaning the survival rate of microorganisms on individual items can be quantified as a probability Although this probability can be minimized to a very low level, it can never reach absolute zero, as indicated by the sterility assurance level.
3.52 sterilization load product to be, or that has been, sterilized together using a given sterilization process
3.53 sterilization process series of actions or operations needed to achieve the specified requirements for sterility
The sterilization process involves pre-treatment of the product when required, exposure to a sterilizing agent under specified conditions, and any necessary post-treatment It is important to note that this process does not encompass any cleaning, disinfection, or packaging operations that occur prior to sterilization.
3.54 sterilization temperature minimum temperature of the sterilization temperature band
3.55 sterilization temperature band range of temperatures, expressed as the sterilization temperature and the maximum permissible temperature which may prevail throughout the sterilization load during the holding time
3.56 sterilizer chamber part of the sterilizer which receives the sterilization load
3.57 sterilizing agent physical or chemical entity, or combination of entities having sufficient microbicidal activity to achieve sterility under defined conditions
3.58 thermal energy energy in the form of heat
3.59 test of sterility technical operation performed as part of development, validation or requalification to determine the presence or absence of viable microorganisms on product or portions thereof
3.60 validation documented procedure for obtaining, recording and interpreting the results required to establish that a process will consistently yield product complying with predetermined specification
3.61 z value temperature change required to effect a ten fold change in D value
Documentation
4.1.1 Procedures for the development, validation, routine control and product release from sterilization shall be specified
Documents and records specified in ISO 17665 must be reviewed and approved by designated personnel, as outlined in section 4.2.1 Additionally, these documents and records should be managed in compliance with the relevant clauses of ISO 13485.
Management responsibility
The implementation and fulfillment of the requirements outlined in ISO 17665 must have clearly defined responsibilities and authority Competent personnel should be designated in accordance with the relevant clauses of ISO 13485.
4.2.2 If the requirements of this part of ISO 17665 are undertaken by organizations with separate quality management systems, the responsibilities and authority of each party shall be specified.
Product realization
4.3.1 Procedures for purchasing shall be specified These procedures shall comply with the applicable clauses of ISO 13485
4.3.2 Procedures for identification and traceability of product shall be specified These procedures shall comply with the applicable clauses of ISO 13485
A system that adheres to the relevant clauses of ISO 13485 or ISO 10012 must be established for the calibration of all equipment, including testing instrumentation, to ensure compliance with the requirements outlined in this section of ISO 17665.
Measurement, analysis and improvement — Control of non-conforming product
Procedures for managing non-conforming products, including correction, corrective actions, and preventive measures, must be clearly defined These procedures should align with the relevant clauses of ISO 13485.
Sterilizing agent
5.1.1 For the purposes of this part of ISO 17665 the sterilizing agent shall be moist heat
5.1.2 Contaminants contained within the sterilizing agent shall not impair the safety of the product for its intended use.
Microbicidal effectiveness
If moist heat is used outside of the range of conditions that are widely recognised, then the microbicidal effectiveness shall be established and documented
NOTE The microbicidal effectiveness of moist heat and its use in sterilization processes has been comprehensively documented and is available in the published literature.
Materials effects
The effect of the sterilizing agent on materials shall be assessed in accordance with the requirements of Clauses 6 and 7.
Environmental consideration
Moist heat is typically not viewed as having a major environmental impact; however, it is essential to evaluate the environmental effects of the sterilization process Any necessary measures to mitigate these effects should be identified and documented, including any potential impacts and control measures.
Process
General
All sterilization processes must be clearly specified, including a detailed description of the operating cycle, process parameters with tolerances, and the applicable product families It is essential to outline any necessary conditioning requirements prior to sterilization, the reference measuring point's location, and the minimum and maximum pressures within the sterilizer chamber Additionally, the rate of pressure change, maximum allowable contaminants, and the process variables for verification should be defined Load configuration and any size or mass restrictions must also be included, along with periodic tests and acceptance criteria to ensure reproducibility The locations and acceptance criteria for biological and chemical indicators should be specified, as well as the minimum cycle lethality achieved and the methods used to determine it Finally, any post-operating cycle treatments included in the sterilization process should be documented.
Saturated steam processes
The specification for a saturated steam sterilization process must include several critical elements: the holding time and temperature range within the sterilizer chamber, including fixed parts; the maximum allowable temperature difference between the reference point and theoretical steam values; a steam penetration test description for products that restrict steam access; the maximum water amount that could be suspended in the steam if it adversely affects product integrity; reference loads for assessing sterilization effectiveness; details about the monitoring device used to verify the sterilization process; and the assessment of the reference load's dryness through mass change or visible moisture.
Contained product processes
The sterilization process specification must include essential information for a sterilization load associated with the identified product family, particularly for the most challenging load configuration This includes details about the product and its container, the size and positioning of the sterilization load within the chamber, and the temperature profiles along with their measurement locations during the operating cycle Additionally, it should specify the maximum and minimum temperatures and their rates of change for the claimed lethality period, as well as the method for determining where these temperature measurements are taken.
Equipment
The sterilization process requires specific equipment, which must be detailed in the specifications This includes the main equipment and any necessary ancillary items, as well as the materials used in the construction of components that contain and transport steam or other gases or liquids into the sterilizer chamber Additionally, each measuring chain utilized for controlling, indicating, monitoring, and recording the sterilization process must be clearly defined.
1) a description of the measuring chain;
2) the characteristics and location of the sensor;
The verification method for calibrating the measuring chain must be traceable to a national calibration standard It is essential to monitor the maximum rate of pressure change and identify any faults recognized by the sterilizing equipment, which should include visual, audio, or recorded warnings Safety features must be in place to control personnel and protect the environment, along with a statement confirming conformity to local, regional, or national emissions regulations If vacuum is utilized during the operating cycle, a detailed description and acceptance criteria for testing air leakage into the sterilizer chamber are required Additionally, if an air detection device is installed, it should be described along with its settings for detecting non-condensable gases, including air, that may be present in the steam supplied to the sterilizer chamber or remain after the air removal stage of the sterilization process.
The operating procedures for equipment and ancillary items must be clearly defined, including the programmed operating cycles in the automatic controller and the process for modifying these programs Detailed step-by-step operating instructions should be provided, along with methods for identifying failures in process parameters and the corresponding corrective actions Additionally, calibration and maintenance instructions are essential, as well as procedures for detecting errors in measurement results for control, indication, or recording Finally, contact information for technical support should be readily available.
The installation location for the equipment must be clearly defined, including the specific site, available space, and environmental conditions Additionally, comprehensive installation instructions should be provided, along with detailed information on all necessary services required for the equipment's proper operation, including any applicable requirements.
6) minimum and maximum voltage and maximum volt amperes;
7) maximum level of non-condensable gas and liquid water in saturated steam;
The article outlines essential considerations for equipment installation, including the maximum allowable levels of contaminants, the structural integrity required to support heavy components, the appropriate materials for transporting steam, gas, air, and water, and the necessity for documentation proving compliance with local, regional, or national environmental emission regulations.
6.2.4 The sterilization load support system in the sterilizer chamber shall not inhibit the uniform attainment of the sterilizing conditions or cause damage to the product and/or its packaging
6.2.5 Means shall be provided to ensure that failure to attain specified process parameters does not lead to an ineffective sterilization process appearing to be effective
The equipment manufacturer must create documented procedures to validate the application of software and any changes made to it, ensuring that these do not compromise the equipment's conformity to its specifications.
7.1 Product to be sterilized shall be specified
7.2 Product packaging systems (if used) shall be specified and shall conform to ISO 11607-1 and
7.3 The product family assigned to the product and its packaging system shall be specified
7.4 The criteria for assigning the product family shall be specified
7.5 If a process challenge device (PCD) is identified as a challenge that can be used to represent the product and its packaging system, it shall be defined
Each process variable related to the product and its packaging system must have specified limiting values These values should encompass all materials and their combinations It is essential to identify the worst-case effects of exposure, or repeated exposure when relevant, to the sterilizing agent under various process parameters, focusing on the impact on the product's physical and chemical characteristics as well as its biocompatibility.
Examples of some process variables include:
⎯ dwell time at the limit values;
⎯ rate of change of pressure;
⎯ rate of change of temperature
NOTE Limiting values for these process parameters are specified, because exceeding the specified values could have an adverse effect on the performance of the product and/or its packaging
The efficiency of the sterilization process can be influenced by the moisture levels in the product and its packaging Therefore, it is essential to specify the limiting values of moisture present before sterilization.
7.8 The stability and potency of a contained product shall not be adversely affected when exposed to the proposed sterilization temperature and exposure time(s)
7.9 If the integrity of the product can be affected by a contaminant(s) remaining on the product after sterilization, the contaminant and the maximum acceptable limit shall be specified
A robust system must be established to ensure that the product and its packaging are in optimal condition for sterilization, safeguarding the effectiveness of the process Key components of this system include: effective cleaning and disinfection, particularly for reusable packaging like rigid sterilization containers; maintaining the integrity of the packaging both before and after sterilization; controlling environmental factors that may affect product bioburden; and, when using a bioburden-based method, estimating the bioburden in line with ISO 11737-1 standards.
The sterilization process must be clearly defined, including its parameters and their limits It is essential to measure physical process parameters during the establishment of this process to ensure reproducibility.
8.2 The minimum level of sterility assurance, SAL, to be achieved by the sterilization process on and/or within a product shall be specified
8.3 The sterilization process shall not expose the product and its packaging system (if used) to process parameters exceeding the levels identified in 7.6 and also to the contaminant(s) identified in 7.9
To ensure effective sterilization of a product using saturated steam, it is crucial that residual air and non-condensable gases do not hinder the steam's contact with all surfaces of the product, including those in cavities, lumens, and tubing, at the start of the holding time.
Biological indicator systems utilized in the sterilization process must adhere to ISO 11138-1 and ISO 11138-3 standards It is essential to identify the microorganism, its population, resistance, and method of presentation, considering the specific sterilization process and the anticipated or established bioburden.
The method of presentation may include inoculated product or the placement of inoculated carrier(s) within the product
Biological indicator systems utilized in the saturated steam sterilization process must adhere to ISO 11138-1 standards, as outlined in sections 8.11 b), c), and/or d).
8.7 For contained product, the effect of the product and its packaging system on the lethality of the test microorganism when exposed to the proposed sterilization process shall be known
Chemical indicators used in the sterilization process must adhere to the relevant sections of the ISO 11140 series Additionally, these indicators should not negatively impact the medical device through reactions, contamination, or transfer at any stage of the sterilization process.
To evaluate the effectiveness of the sterilization process for the product mentioned in Clause 7, it is essential to establish and document the validity of the Process Challenge Device (PCD), the testing methodologies, and the acceptance criteria.
8.10 The sterilization process shall be established from at least one of the following:
⎯ data supplied by the medical device manufacturer, and/or packaging material manufacturer and/or the sterilizer manufacturer (see ISO 17664);
⎯ similarity with a product that is already assigned to a product family;
⎯ development of an operating cycle that will deliver the specified SAL
General
9.1.1 Each stage of validation shall be carried out in accordance with a documented procedure
9.1.2 It shall be verified that each item of fixed and portable equipment used during validation complies with its specification
9.1.3 Any modifications to product, equipment, or sterilization process carried out during validation shall be recorded and justified, and the specification(s) changed accordingly (see also 12)
9.1.4 The measuring chain for each test instrument used for validation shall have:
⎯ calibration traceable to a national standard;
⎯ a valid maintenance certificate (if appropriate);
⎯ a calibration status verified according to the technical and applicable management requirements;
⎯ verification of calibration carried out at a value(s) used to control the sterilization process and judge the results of the test in which the measuring chain is used
9.1.5 The correlation between readings indicated and recorded by instruments fitted to the sterilizer and readings registered by independent test instruments having sensors in similar locations shall be verified
9.1.6 It shall be verified during installation qualification (IQ), operational qualification (OQ) or performance qualification (PQ), as applicable, that fault recognition systems function and comply with their performance specifications
When utilizing an existing sterilizer and sterilization process for a new product, the IQ and OQ validation stages can be skipped, as long as no modifications are made to the equipment or the current sterilizer loads that could impact the effectiveness of the sterilization process.
9.1.8 The validity of the proposed periodic test(s) shall be verified [see 6.1.1 l) and 10.3].
Installation qualification (IQ)
Equipment
It shall be verified that the equipment and documentation comply with 6.2.1, 6.2.2 and 6.2.3 and that services comply with 6.2.3.
Installation
It shall be verified that the installation complies with 6.2.3.
Function
It is essential to confirm that the equipment and operational safety systems outlined in section 6.2.1 operate according to their specifications Additionally, the operating cycle(s) must comply with section 6.1.1 a), and there should be no signs of leakage from the services or equipment.
Operational qualification (OQ)
9.3.1 Operational qualification shall demonstrate that installed equipment will deliver the sterilization process defined in 8, and shall establish data for each requirement (if applicable) listed in 6.1
The documentation must include the reasoning behind the selection and placement of temperature sensors to ensure compliance with temperature distribution requirements in an empty sterilizer chamber, including its fixed components, as well as in the presence of a test load, if applicable.
Performance qualification (PQ)
9.4.1 Performance qualification shall demonstrate that product has been exposed to the specified sterilization process by the equipment to be used for routine sterilization
9.4.2 Rationale shall be documented for the number and locations of temperature sensors used to demonstrate that requirements are met in the sterilization load
Checks must ensure that documentation verifies successful Installation Qualification (IQ) and Operational Qualification (OQ) The test sterilization load should consist of products that are routinely processed and belong to compatible product families, particularly those that pose the greatest challenge to the sterilization process Additionally, the packaging system must match that used in regular production or reprocessing Pre-conditioning must adhere to the specified requirements, and the load configuration should be the most challenging to sterilize, in accordance with established guidelines Finally, the size and mass of the sterilization load must meet the specified criteria.
9.4.4 For each of the following, studies shall establish; a) conformity to the sterilization process identified in Clause 8 and the limiting process values identified in
The article outlines the necessary data requirements for sterilization processes, including exposure profiles at specified positions, holding times, and temperature measurements It emphasizes the importance of documenting minimum and maximum temperatures during the sterilization load, as well as the temperature profiles during the plateau period of the identified processes.
⎯ measured at the reference measuring point;
⎯ measured on or within the sterilization load;
⎯ determined from the sterilizer chamber pressure;
When establishing the maximum allowable discrepancy between measured and calculated temperatures, it is essential to consider national or regional standards, such as EN 285 Additionally, the performance of chemical indicators and the response of the process challenge device (PCD) should be evaluated, along with the integrity of the packaging system utilized.
In addition to measuring physical parameters, the sterilization process should also consider bioburden and microbiological verification To ensure effectiveness, biological indicators must be strategically placed in and/or on the product at specified locations, as outlined in section 9.4.4, and subsequently exposed to the sterilization method.
The treatment applied is less intense than that used in the sterilization process, yet it effectively demonstrates that the minimum microbicidal effectiveness requirements are satisfied when the sterilization process is implemented.
The treatment conducted at the lower tolerances of the sterilization process parameters confirms that the specified requirements for minimum microbicidal effectiveness are achieved.
PQ must consist of a minimum of three consecutive exposures of the sterilization load to the sterilization process, ensuring adherence to the sterilization process specifications and demonstrating the reproducibility of the sterilization process.
9.4.7 Non-compliance with the sterilization process specification during PQ shall be reviewed and corrected
If a failure is linked to factors unrelated to the validated sterilization process, it can be recorded as not affecting the sterilization performance, eliminating the need for three additional consecutive exposures.
EXAMPLE Power failure, loss of services and failure of external monitoring equipment.
Review and approval of validation
During the validation process, all information collected or generated during Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) must be assessed for compliance with the established acceptance criteria for each phase The results of this evaluation should be thoroughly documented and receive formal approval.
A sterilization process specification must be confirmed, detailing process parameters and tolerances This specification should outline the criteria for designating a sterilization process as conforming for a specific sterilizer load and must document the following: the applicable product families, load configurations, size and mass of the sterilization load, pre-conditioning procedures, packaging system and methods, distribution of medical devices within multi-device packages, periodic tests, relevant process challenge devices, and applicable bioburden.
10.1 Routine monitoring and control shall be performed on each operating cycle
10.2 Evidence of successful maintenance and requalification (if applicable) shall be verified
To ensure the operational status of the equipment, periodic tests must provide evidence of various factors, including air leakage into the sterilizer chamber, the quality of saturated steam or heat transfer media, and checks for non-condensable gases and contaminants Additionally, it is essential to verify the functionality of automatic controls and the effectiveness of steam penetration, as well as to confirm that the sterilization process remains consistent and reproducible.
The verification of the sterilization process will be conducted through the results of chemical indicators or biological indicator systems, if applicable Additionally, it is essential to confirm that the recorded data from routine monitoring aligns with the validation data within specified tolerances.
For saturated steam processes, essential data must include the sterilization temperature, chamber pressure, and theoretical steam temperature during the plateau period, along with the duration of this plateau Additionally, it is important to record the chamber temperature and pressure for each stage of the operating cycle, the results from a process challenge device, and any temperatures or pressures from a process monitoring system used for process control.
For contained product processes, it is essential to include specific data such as the temperature measurements from the reference challenge device used for process control, the chamber temperature and pressure profiles during heating, exposure, and cooling, as well as the temperature profiles for the product during these phases in designated positions.
In the context of process control, it is essential to consider the plateau period or holding time, the values for the process parameters that ensure homogeneity of the heating media within the sterilizer chamber, and the results from inspecting the sterilization load to verify the dryness and integrity of the packaging system.
10.7 All records shall be retained in accordance with 4.1.2
Procedures for reviewing records and releasing products from the sterilization process must be clearly defined These procedures should outline the necessary requirements for a sterilization process to be considered conforming If any requirement is not satisfied, the product will be classified as non-conforming and managed according to established protocols.
11.2 A system shall be specified to ensure that processed and non-processed items are clearly differentiated
Demonstration of continued effectiveness
12.1.1 Product presented for sterilization shall comply with a) the product definition in Clause 7; b) the load configuration as defined in 6.1.1 j); c) the size and mass criteria defined in 6.1.1 k)
12.1.2 Successful completion of periodic tests, calibrations, maintenance tasks and requalification carried out at specified intervals shall be verified
12.1.3 The quality of the environment in which the product is prepared and/or packaged shall be periodically verified
12.1.4 Requirements for the health, cleanliness and clothing of personnel in the manufacturing and/or packaging area shall be specified and enforced
12.1.5 If the sterilization process makes use of a vacuum, an air leakage test shall be carried out at specified intervals
To ensure effective sterilization, a steam penetration test must be conducted daily before using the sterilizer, especially when the process depends on removing air from the chamber for optimal steam distribution.
The steam penetration test utilizes a device designed to assess air removal and steam penetration during sterilization processes In industrial settings, when using saturated steam with established sterilization loads that do not obstruct steam penetration, alternative methods may be employed These alternatives are based on specific physical measurements and a thorough risk assessment of potential process failures.
12.1.7 Product shall conform to bioburden requirements, if applicable.
Recalibration
The accuracy and reliability of each measuring chain used to control, indicate, or record the sterilization process shall be verified periodically in accordance with 4.3.3.
Maintenance of equipment
12.3.1 Preventative maintenance shall be planned and performed in accordance with documented procedures
12.3.2 Equipment shall not be used to process product until all specified maintenance tasks have been satisfactorily completed and recorded
12.3.3 The maintenance plan, maintenance procedures and maintenance records shall be retained
(see 4.1.2) and reviewed at specified intervals by a designated person The results of the review shall be documented.
Requalification
Requalification of a sterilization process must be performed for specific products and equipment at set intervals, as well as following any changes The justification for the extent of requalification should be clearly established.
12.4.2 Requalification procedures shall be specified and records of requalification retained (see 4.1.2)
Requalification data must be evaluated against established acceptance criteria following documented procedures It is essential to maintain records of these evaluations, including any corrections and corrective actions taken.
Assessment of change
Any modifications must be evaluated for their potential impact on the sterilization process's effectiveness Considerations for changes include the replacement of parts that may alter process parameters, increase leakage into the sterilizer chamber, or affect homogeneity within the chamber Additionally, any new or modified software and hardware, adjustments to process parameters, maintenance service outcomes, changes in packaging or packaging procedures, load configurations, and variations in product materials, sources, or designs should also be assessed.
The results of this assessment, along with the reasoning behind the decisions made and any modifications to the sterilization process, product, or requalification requirements, must be thoroughly documented.
The guidance in this annex is not a compliance checklist for ISO 17665 but aims to foster a consistent understanding and implementation of its requirements It offers explanations and acceptable methods for compliance, while alternative methods may also be utilized, provided they are proven effective in meeting the standards of ISO 17665.
NOTE 2 For ease of reference the numbering in this annex corresponds to that in the normative part of this part of ISO 17665
Effective implementation of documented procedures is crucial for the development, validation, and routine control of sterilization processes for medical devices These procedures are integral to a quality management system, as outlined in ISO 17665, which specifies essential elements for effective sterilization control by referencing ISO 13485 It is important to note that a complete quality management system compliant with ISO 13485 is not mandatory, nor is third-party assessment of the specified elements required Additionally, national and regional regulatory requirements for quality management systems in medical device manufacturing and third-party assessments should be considered.
The requirements outlined in normative references are applicable to this section of ISO 17665 only to the extent that they are specifically cited, whether referencing the entire standard or particular clauses.
Requirements for control of documents and records are specified in 4.2.3 and 4.2.4 of ISO 13485:2003, respectively
In ISO 13485:2003, the requirements for documentation relate to the generation and control of documentation
(including specifications and procedures) and records
Requirements for responsibility and authority are specified in 5.5 of ISO 13485:2003, and requirements for human resources are specified in 6.2 of ISO 13485:2003
In ISO 13485, the requirements for management responsibility relate to management commitment, customer focus, quality policy, planning, responsibility, authority and communication and management review
The development, validation, and routine control of a sterilization process involve multiple parties, each responsible for specific elements According to ISO 17665, it is essential to clearly define and document the responsibilities of these parties within their quality management systems The designated party must assign these responsibilities to qualified personnel, ensuring their competence through appropriate training and qualifications.
ISO 13485 outlines the requirements for product realization throughout the entire product lifecycle, encompassing the identification of customer needs, design and development processes, procurement, production control, and the calibration of monitoring and measuring devices.
According to section 7.4 of ISO 13485:2003, specific requirements for purchasing are outlined, emphasizing that the verification requirements in section 7.4.3 apply to all products and services acquired from external sources.
A.4.3.2 Requirements for identification and traceability are specified in 7.5.3 of ISO 13485:2003
A.4.3.3 Requirements for calibration of monitoring and measuring devices are specified in 7.6 of
A.4.4 Measurement, analysis and improvement — Control of nonconforming product
Procedures for control of non-conforming product and corrective action are specified in 8.3 and 8.5.2 of
In ISO 13485, the requirements for measurement, analysis and improvement relate to process monitoring, control of nonconforming product, analysis of data, and improvement (including corrective and preventive actions)
This activity aims to evaluate the sterilizing agent by characterizing its properties, demonstrating its effectiveness against microbes, assessing its impact on various materials, and identifying safety requirements for personnel and environmental protection.
This activity may be undertaken in a test or prototype system; the final equipment specification should be relatable to the experimental studies undertaken using any such test or prototype system
The purpose of this activity is to characterize the entire sterilization process and the equipment necessary to deliver the sterilizing process safely and reproducibly
A sterilization process must be defined for specific product families and loading configurations, detailing the process parameters that outline the exposure profile during the operating cycle and those used to ensure reproducibility It is essential to identify the exposure duration that establishes lethality and to define the upper and lower limits of each process parameter that influences both lethality and product performance The sterilization process specification, along with the equipment used, should provide enough detail to be considered in the process definition section when proposing a new product or loading configuration.
This activity aims to identify the product designated for sterilization, focusing on its microbiological quality, known as bioburden, before the sterilization process Additionally, it addresses how the product is packaged and presented for effective sterilization.
The materials selected for product construction and packaging must endure the typical parameters of moist heat processes It is essential to identify any limitations imposed by the product design and the materials utilized.
The goal of this activity is to establish a comprehensive specification for the sterilization process of a defined product, ensuring that its safety, quality, and performance remain uncompromised.
The sterilization process can be recognized through validated equipment designed for products within the same family This identification may come from the product manufacturer or be specifically developed for the assigned product family It is essential to adhere to the defined limits on process parameters and exposure restrictions outlined in the product specifications.
Examples of operating cycles are illustrated in Annex E
Validation ensures that the sterilization process is effectively and consistently applied to the sterilization load It involves several key stages: installation qualification, operational qualification, and performance qualification During installation qualification, compliance with equipment, services, and installation specifications is verified Operational qualification confirms the delivery of the specified sterilization process, while performance qualification establishes the achievement of the required Sterility Assurance Level (SAL) on the product.