Sterilization of health-care products—Ethylene oxide—Requirements for the development,validation and routine control of a sterilization process for medical devices
Sterilization of health-care products - Ethylene oxide - Requirements for the development, validation and routine control of a sterilization process for medical devices
1 Scope
1.1 Inclusions
This document specifies requirements for the development, validation and routine control of an ethylene oxide sterilization process for medical devices during manufacture, and it is applicable to medical devices adopting EO for sterilization.
Note 1: There are similarities and differences in the development, validation and routine control of an ethylene oxide sterilization process in both the product manufacturing process and health care facilities, please refer to this document for EO sterilization process in health care facilities. Among the similarities are the common need for quality systems, staff training, and proper safety measures. The major differences relate to the unique physical and organizational conditions in health care facilities, and to the initial condition of reusable medical devices being presented for sterilization.
Note 2: Health care facilities differ from medical device manufacturers in the physical design of processing areas, in the equipment used, and in the availability of personnel with adequate levels of training and experience. The primary function of the health care facility is to provide patient care; medical device reprocessing is just one of a myriad of activities that are performed to support that function.
Note 3: In terms of the initial condition of medical devices, medical device manufacturers generally sterilize large numbers of similar medical devices that have been produced from virgin material. Health care facilities, on the other hand, shall handle and process both new medical devices and reusable medical devices with varying levels of bioburden. They are therefore faced with the additional challenges of cleaning, evaluating, preparing and packaging a medical device prior to sterilization. In this document, alternative approaches and guidance on the development, validation and control of sterilization process specific to health care facilities are recommended.
Note 4: EO gas and its mixtures are effective sterilants that are primarily used for heat- and/or moisture-sensitive medical devices that cannot be moist heat sterilized.
Note 5: Although the scope of this document is limited to medical devices, it specifies requirements and provides guidance that may be applicable to other health care products.
1.2 Exclusions
1.2.1 This document does not specify requirements for the development, validation and routine control of a process for inactivating the causative agents of spongiform encephalopathies such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease.
Note: See YY/T 0771.1, YY/T 0771.2 and YY/T 0771.3.
1.2.2 This document does not detail a specified requirement for designating a medical device as sterile.
1.2.3 This document does not specify a quality management system for the control of all phases of production of medical devices.
Note: The effective implementation of defined and documented procedures is necessary for the development, validation and routine control of a sterilization process for medical devices. Such procedures are commonly considered to be elements of a quality management system. It is not a requirement of this document to have a full quality management system during manufacture or reprocessing. The necessary elements are normatively referenced at appropriate places in this document (see, in particular, Clause 4). Attention is drawn to the standards for quality management systems (see YY/T 0287-2017) that control all phases of production or reprocessing of medical devices.
1.2.4 This document does not specify requirements for occupational safety associated with the design and operation of EO sterilization facilities.
Note: EO is toxic, flammable and explosive. For further information on safety, see examples in the Bibliography.
1.2.5 This document does not cover sterilization by injecting EO or gas mixtures directly into packages or a flexible chamber.
1.2.6 This document does not cover analytical methods for determining levels of residual EO and/or its reaction products.
Note: For further information, see GB/T 16886.7-2015.
2 Normative references
The following documents contain requirements which, through reference in this text, constitute provisions 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.
GB 18281.1-2015 Sterilization of health care products - Biological indicators - Part 1:General requirements (ISO 11138-1: 2006, IDT)
GB 18281.2-2015 Sterilization of health care products - Biological indicators - Part 2: Biological indicators for ethylene oxide sterilization processes (ISO 11138-2: 2006, IDT)
GB 18282.1 Sterilization of health care products - Chemical indicator - Part 1:General requirements (GB 18282.1-2015, ISO 11140-1: 2005, IDT)
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
aeration
part of the sterilization process during which ethylene oxide and/or its reaction products desorb from the medical device until predetermined levels are reached
Note: This may be performed within the sterilizer and/or in a separate chamber or room.
3.2
aeration area
either a chamber or a room in which aeration occurs
3.3
bioburden
population of viable microorganisms on or in product and/or sterile barrier system
[Source: GB/T 19971-2015, definition 2.2]
3.4
biological indicator
test system containing viable microorganisms providing a defined resistance to a specified sterilization process
[Source: GB/T 19971-2015, definition 2.3]
3.5
calibration
set of operations that establish, under specified conditions, the relationship between values of a quantity indicated by a measuring instrument or measuring system, or values represented by a material measure or a reference material, and the corresponding values realized by standards
[Source: GB/T 19971-2015, definition 2.4]
3.6
chemical 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 sterilization process
[Source: GB/T 19971-2015, definition 2.6]
3.7
conditioning
treatment of product within the sterilization cycle, but prior to ethylene oxide admission, to attain a predetermined temperature and relative humidity
Note 1: This phase may be carried out either at atmospheric pressure or under vacuum.
Note 2: See 3.26 “Preconditioning”.
3.8
D value
D10 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 document, the D value is the exposure time required to achieve 90% inactivation of the population of the test organism.
[Source: GB/T 19971-2015, definition 2.11]
3.9
development
act of elaborating a specification
[Source: GB/T 19971-2015, definition 2.13]
3.10
dew point
temperature at which the saturation steam pressure is equal to the partial pressure of the steam in the atmosphere
Note: Any cooling of the atmosphere below the dew point would produce water condensation.
3.11
establish
determine by theoretical evaluation and confirm by experimentation
[Source: GB/T 19971-2015, definition 2.17]
3.12
ethylene oxide injection time
duration of the phase beginning with the first introduction of the EO (or gas mixture) into the chamber to the completion of that injection
3.13
exposure time
period for which the process parameters are maintained within their specified tolerances
Note: For the purpose of calculation of cycle lethality, it is the period of sterilization between the end of EO injection and the beginning of EO removal in this document.
[Source: GB/T 19971-2015, definition 2.18]
3.14
fault
one or more of the process parameters lying outside of its/their specified tolerance(s)
[Source: GB/T 19971-2015, definition 2.19]
3.15
flushing
procedure by which the ethylene oxide is removed from the load and chamber by
a) multiple alternate admissions of filtered air, inert gas or steam and evacuations of the chamber, or
b) continuous passage of filtered air, inert gas or steam through the load and chamber
3.16
fractional cycle
a cycle in which the exposure time is reduced compared to that specified in the sterilization process
3.17
half cycle
a cycle in which the exposure time is reduced by 50% compared to that specified in the sterilization process
3.18
health care facility; HCF
governmental and private organizations and institutions devoted to the promotion and maintenance of health, and the prevention and treatment of diseases and injuries
Example: A health care facility may be a hospital, nursing home, extended care facility, free-standing surgical center, clinic, medical office, or dental office.
3.19
health care product
medical device(s), including in vitro diagnostic medical device(s), or medicinal product(s), including biopharmaceutical(s)
[Source: GB/T 19971-2015, definition 2.20]
3.20
installation qualification; IQ
process of obtaining and documenting evidence that equipment has been provided and installed in accordance with its specification
[Source: GB/T 19971-2015, definition 2.22]
3.21
microorganism
entity of microscopic size, encompassing bacteria, fungi, protozoa and viruses
Note: A specific standard might not require demonstration of the effectiveness of the sterilization process in inactivating all types of microorganisms, identified in the definition above, for validation and/or routine control of the sterilization process.
[Source: GB/T 19971-2015, definition 2.26]
3.22
operational qualification; OQ
process of obtaining and documenting evidence that installed equipment operates within predetermined limits when used in accordance with its operational procedures
[Source: GB/T 19971-2015, definition 2.27]
3.23
overkill approach
approach using sterilization process that delivers a minimum of 12 spore-log-reduction (SLR) to a biological indicator having a resistance equal to or greater than the product bioburden
3.24
parametric release
declaration that product is sterile, based on records demonstrating that the process parameters were delivered within specified tolerances
Note: This method of process release does not include the use of biological indicators.
[Source: GB/T 19971-2015, definition 2.29]
3.25
performance qualification; PQ
process of obtaining and documenting evidence that the equipment, as installed and operated in accordance with operational procedures, consistently performs in accordance with predetermined criteria and thereby yields product meeting its specification
[Source: GB/T 19971-2015, definition 2.30]
3.26
preconditioning
treatment of product, prior to the sterilization cycle, in a room or chamber to attain specified conditions for temperature and relative humidity
3.27
process challenge device; PCD
item designed to constitute a defined resistance to a sterilization process and used to assess performance of the process
Note 1: For the purpose of this document, a PCD may be product, simulated product or other device that is inoculated directly or indirectly. See 7.1.6 and D.7.1.6.
Note 2: In this document, a distinction is made between an internal PCD and an external PCD. An internal PCD is used to demonstrate that the required product SAL is achieved. A PCD located within the confines of the product or product shipper case is an internal PCD, whereas a PCD located between shipper cases or on the exterior surfaces of the load is an external PCD. An external PCD is an item designed to be used for microbiological monitoring of routine sterilization cycles.
[Source: GB/T 19971-2015, definition 2.33]
3.28
process parameter
specified value for a process variable
Note: The specification for a sterilization process includes the process parameters and their tolerances.
[Source: GB/T 19971-2015, definition 2.34]
3.29
process variable
condition within a sterilization process, changes in which alter microbicidal effectiveness
Example: Time, temperature, pressure, concentration, humidity, wavelength.
[Source: GB/T 19971-2015, definition 2.35]
3.30
processing category
collection of different product or product families that may be sterilized together
Note: All products within the category have been determined to present an equal or lesser challenge to the sterilization process than the process challenge device for that category.
3.31
product
result of a process
Note: For the purposes of sterilization standards, product is tangible and may be raw material(s), component(s), intermediate(s) and health care products.
[Source: GB/T 19971-2015, definition 2.36]
3.32
product family
group of product possessing characteristics that allow them to be sterilized using defined process conditions
3.33
product load volume
defined space within the usable chamber volume occupied by product
3.34
recognized culture collection
depository authority under the Budapest Treaty on “The International Recognition of the Deposit of Microorganisms for the Purposes of Patent and Regulation”
[Source: GB/T 19971-2015, definition 2.38]
