GB 18279-2023 PDF English
Search result: GB 18279-2023 English: PDF
| Standard ID | Contents [version] | USD | STEP2 | [PDF] delivered in | Name of Chinese Standard | Status |
| GB 18279-2023 | English | 905 |
Add to Cart
|
0-9 seconds. Auto-delivery.
|
Sterilization of health-care products - Ethylene oxide - Requirements for the development, validation and routine control of a sterilization process for medical devices
| Valid |
| GB 18279.1-2015 | English | 555 |
Add to Cart
|
0-9 seconds. Auto-delivery.
|
Sterilization of health care products -- Ethylene oxide -- Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices
| Valid |
| GB 18279-2000 | English | RFQ |
ASK
|
4 days
|
Medical devices. Validation and routine control of ethylene oxide sterilization
| Obsolete |
PDF Preview: GB 18279-2023
PDF Preview: GB 18279.1-2015
GB 18279-2023: PDF in English GB 18279-2023
GB
NATIONAL STANDARD OF THE
PEOPLE’S REPUBLIC OF CHINA
ICS 11.080.01
CCS C 47
Replacing GB 18279.1-2015, GB/T 18279.2-2015
Sterilization of health-care products - Ethylene oxide -
Requirements for the development, validation and routine
control of a sterilization process for medical devices
(ISO 11135:2014, MOD)
ISSUED ON: SEPTEMBER 08, 2023
IMPLEMENTED ON: OCTOBER 01, 2026
Issued by: State Administration for Market Regulation;
Standardization Administration of the People's Republic of China.
Table of Contents
Foreword ... 3
Introduction ... 6
1 Scope ... 8
2 Normative references ... 9
3 Terms and definitions ... 10
4 Quality management system ... 19
5 Characteristics of sterilizing agents ... 20
6 Process and device characteristics ... 21
7 Product definition ... 23
8 Process definition ... 25
9 Validation ... 26
10 Routine monitoring and control ... 33
11 Sterilization release of products ... 34
12 Maintenance of effectiveness of sterilization process ... 35
Annex A (normative) Determination of kill rate of sterilization process - Biological
indicator/bioburden method ... 37
Annex B (normative) Method for determining conservativeness of kill rate in
sterilization process - Overkill approach ... 40
Annex C (informative) Temperature sensors, humidity sensors and biological indicators
... 42
Annex D (informative) Guidance on the application of normative requirements ... 46
Annex E (normative) Single batch release ... 95
Bibliography ... 99
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 Application
This document specifies the development, validation and routine control requirements
for the ethylene oxide sterilization process during the manufacturing process of medical
device products. It is applicable to medical devices sterilized by ethylene oxide.
NOTE 1: There are similarities and differences in the development, validation, and routine control
of sterilization processes in product manufacturing and health care facility. This document can be
used as a reference for ethylene oxide sterilization processes in health care facility. The similarities
are the general requirements for quality systems, personnel training, and appropriate safety measures.
The main differences involve the unique physical and organizational conditions of health care
facility, as well as the initial conditions of reusable medical devices for sterilization.
NOTE 2: Health care facilities differ from medical device manufacturers in the hardware design of
sterilization areas, the equipment used, and the personnel with adequate training and experience.
The primary function of a health care facility is to provide health care services to patients.
Reconditioning of medical devices is only one of countless activities that support this function.
NOTE 3: In terms of the initial condition of medical devices, medical device manufacturers
typically sterilize batches of similar medical devices starting from virgin materials. On the other
hand, health care facilities handle and process both new and reused medical devices with varying
bioburden levels and are therefore faced with the additional challenge of cleaning, evaluating,
preparing, and packaging medical devices prior to sterilization. This document recommends
alternative approaches and guidance for the development, validation, and control of sterilization
processes for health care facilities.
NOTE 4: Ethylene oxide gas and its mixtures are effective sterilants, mainly used for medical
devices that are sensitive to heat and/or moisture and cannot be sterilized by moist heat.
NOTE 5: Although this document is limited to medical devices, the requirements specified and
guidance provided by the standard may also be applicable to other health care products.
1.2 In-application
1.2.1 This document is not applicable to the development, validation and routine control
of processes for inactivating the causative agents of spongiform encephalopathies (e.g.,
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 specify specific requirements for medical devices labeled
as sterile.
1.2.3 This document does not specify a quality management system that controls all
stages of production of medical devices.
NOTE: The development, validation and routine control of sterilization processes for medical
devices require the effective implementation of defined and documented procedures. These
procedures are usually elements of a quality management system. This document does not require
a complete quality management system to be in place during manufacturing or reprocessing.
Necessary elements are normatively referenced at appropriate locations in this document (Chapter
4). Attention shall be paid to the quality management system standards that control all stages of
medical device production or reprocessing (see YY/T 0287-2017).
1.2.4 This document does not specify occupational safety requirements related to the
design and operation of ethylene oxide sterilization facilities.
NOTE: Ethylene oxide is toxic, flammable and explosive. For more information on safety, see
references.
1.2.5 This document does not cover sterilization by direct injection of ethylene oxide
or its gas mixtures into product packaging or flexible chambers.
1.2.6 This document does not contain analytical methods for determining residual levels
of ethylene oxide and/or its reaction products.
NOTE: For detailed information, see GB/T 16886.7-2015.
2 Normative references
The following referenced documents are indispensable for the application 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)
4.3.2 Product identification and traceability procedures shall be specified.
NOTE: These procedures are described in the applicable provisions of YY/T 0287-2017.
4.3.3 Calibration procedures for all equipment (including test instruments) used to meet
the requirements of this document shall be specified.
NOTE: For procedures, see the applicable provisions of YY/T 0287-2017 or GB/T 19022-2003.
4.4 Measurement, analysis and improvement - Nonconforming product control
Procedures shall be defined for the control of nonconforming product and for correction,
corrective action and preventive action.
NOTE: These procedures are described in the applicable provisions of YY/T 0287-2017.
5 Characteristics of sterilizing agents
5.1 General
The purpose of this clause is to define the sterilization agent, specify its sterilization
effect, identify factors that affect sterilization effect, evaluate the effects of the sterilant
on materials, and identify requirements for personnel safety and environmental
protection. These activities may be undertaken by test or prototype systems. Regardless
of where they are performed, the final device specification (see 6.3) shall be consistent
with the results of the test or prototype device studies. The sterilization agent referred
to in this document is ethylene oxide.
5.2 Sterilant
If applicable, the sterilant specification shall include the required storage conditions for
ethylene oxide during its shelf life.
5.3 Effectiveness in killing microorganisms
If ethylene oxide outside the recognized composition range is used or a new diluent is
used, data on microbiological effectiveness shall be developed.
NOTE: The microbial inactivation performance of ethylene oxide is well documented in the
literature. This literature provides knowledge of the effects of process variables on microbial
inactivation. This document does not claim to reference such comprehensive studies of microbial
inactivation.
5.4 Material impact
The effects of ethylene oxide on most materials used to manufacture medical devices
have been thoroughly documented. This documentation is valuable in the design and
development of medical devices that are sterilized using ethylene oxide. This document
does not require specific studies on the effects of ethylene oxide on materials, but does
require studies on the effects of ethylene oxide on products (see Chapter 7).
5.5 Safety and environment
5.5.1 Material Safety Data Sheet (MSDS) or similar safety information shall be
provided for ethylene oxide and its diluent (if any). Necessary measures to protect
personnel safety and health shall be identified.
5.5.2 The potential impact of the sterilization process on the environment shall be
assessed and measures to protect the environment shall be identified. The assessment
including potential impacts and control measures shall be documented.
5.5.3 Attention shall be paid to the discharge and conditioning of ethylene oxide, its
diluents and any by-products.
6 Process and device characteristics
6.1 General
6.1.1 The purpose of this clause is to define the complete sterilization process necessary
and the equipment necessary to enable the sterilization process to be carried out safely
and reproducibly.
6.1.2 If a process already exists for sterilizing the product, this activity is not necessary.
However, the sterilization process and equipment shall be reviewed to ensure that the
variables defined in 6.2 and 6.3 are included in the process specifications for routine
production.
6.2 Process characteristics
6.2.1 Process characteristics, which shall at least include:
a) identification of the necessary stages of the ethylene oxide sterilization process;
b) identification of the process variables at each stage;
c) documentation of the process variables.
NOTE: Data developed during product definition (see Chapter 7) may influence the characteristics
of the sterilization process.
6.2.2 The stages of the sterilization process include:
a) preconditioning (if used);
chamber;
d) Description of the instruments used to monitor, control and record the sterilization
process, including sensor characteristics and locations;
e) Faults that can be identified by the sterilization equipment;
f) Safety features, including those for personal safety and environmental protection;
g) Installation requirements, including specifications for required services and
emission control requirements.
6.3.3 Software used for process control and/or monitoring shall be prepared and
validated in accordance with the requirements of the quality system elements. Written
evidence shall be provided to demonstrate that the software conforms to its design
specifications.
NOTE: For detailed information, see GB/T 19003-2018.
6.3.4 Methods for monitoring and controlling process variables shall be determined and
specified.
6.3.5 Methods shall be provided to ensure that failure of control functions does not
result in invalid process parameter records and to avoid invalid processes being
displayed as valid processes.
NOTE: Identification of deviations and indication of faults can be achieved by using independent
control and monitoring systems, or by mutual checking between control and monitoring systems.
7 Product definition
7.1 General
7.1.1 The purpose of this chapter is to define the products to be sterilized, including
their microbiological characteristics prior to sterilization and the packaging and
presentation of the products prior to sterilization.
7.1.2 A product definition shall be performed before introducing a new or changed
product, package or containment method. Demonstration of equivalence to previously
validated products, packages or containment methods (with reference to the challenge
of the sterilization process) shall be considered to satisfy the requirements of the
product definition. This demonstration of equivalence shall be documented.
7.1.3 The design of the product shall allow for the exclusion of air and, where applicable,
the penetration of heat, moisture and ethylene oxide during the sterilization process, as
well as the removal of ethylene oxide at the end of the process.
7.1.4 The design of the packaging shall allow for the exclusion of air, the penetration
of heat, moisture and ethylene oxide during the sterilization process, and the removal
of ethylene oxide at the end of the process.
7.1.5 The product loading pattern shall be designed to allow for the exclusion of air, the
penetration of heat, moisture and ethylene oxide during the sterilization process, and
the removal of ethylene oxide at the end of the process.
7.1.6 It shall be demonstrated that the specified sterilization process is effective in
sterilizing the most difficult-to-sterilize locations of the product. This can be achieved
through process definition and new product validation; or through demonstration of
equivalence with an already validated product; or through the use of an in-house process
challenge device to demonstrate that the specified sterilization process can meet the
product sterility assurance level requirements (see 8.6).
7.2 Product safety, quality and performance
7.2.1 The sterilization process shall be defined using the process parameters and
tolerances that have been identified as having the greatest impact on the
product/package. Confirm that the product and its packaging meet the specified safety,
quality and performance requirements.
NOTE: Design control in YY/T 0316-2016 is one aspect.
7.2.2 If multiple sterilization cycles are permitted, the effects of such conditionings on
the product and packaging shall be evaluated.
7.2.3 The biological safety of the product after exposure to the sterilization process shall
be determined.
NOTE: See GB/T 16886 (all parts).
7.2.4 A method to reduce the residual amount of ethylene oxide shall be established.
NOTE: See the requirements of GB/T 16886.7-2015.
7.3 Microbiological characteristics
7.3.1 A system shall be established and maintained to ensure that the microbiological
characteristics and cleanliness of products intended for sterilization are kept under
control and do not compromise the effectiveness of the sterilization process.
NOTE: The ethylene oxide sterilization process cannot eliminate bacterial endotoxins. The
Pharmacopoeia of the People's Republic of China provides guidance for bacterial endotoxin testing.
7.3.2 For single-use medical devices, the bioburden shall be estimated at specified time
intervals. For reusable medical devices, the effectiveness of the specified cleaning
process and disinfection process (if applicable) shall be evaluated.
8.7 Commercial biological indicators used in sterilization process definition shall
comply with the requirements of 8.6 and all applicable clauses in GB 18281.1-2015.
8.8 If chemical indicators are used in the sterilization process definition, they shall
comply with the requirements of GB 18281.1-2015. Chemical indicators shall not be
used as the only way to establish a sterilization process, nor shall they be used as an
indicator of achieving the specified sterility assurance level.
8.9 Test of sterility may be performed during the sterilization process definition.
NOTE: For test of sterility, see GB/T 19973.2.
9 Validation
9.1 General
9.1.1 The purpose of validation is to demonstrate that the sterilization process
established in the process definition (see Chapter 8) can effectively and reproducibly
sterilize the product in the sterilization load. Validation consists of a number of defined
stages: installation qualification, operational qualification and performance
qualification. Testing shall begin after the validation procedures and/or protocols have
been approved.
9.1.2 The installation qualification shall demonstrate that the sterilization equipment
and its ancillary facilities have been provided and installed in accordance with their
specifications.
9.1.3 Operational qualification shall demonstrate that the equipment can meet the
performance requirements of the design specifications.
9.1.4 Performance qualification shall be conducted using the product to demonstrate
that the equipment can continue to operate in accordance with the predetermined
acceptance criteria and that the sterilization process is capable of rendering the product
sterile and meeting the specified requirements.
For the equipment used in sterilization process, only one installation qualification and
one operational qualification may be carried out for the designated equipment. Each
new product and/or process to be confirmed shall be subject to performance
qualification to prove that the sterilization process meets the specified acceptance
criteria and can achieve the sterility assurance level required by the product.
9.2 Installation qualification
9.2.1 Equipment
9.2.1.1 Equipment used for the sterilization process, including any ancillary facilities,
shall comply with the design specifications.
9.2.1.2 Sterilization equipment shall comply with applicable safety standards.
9.2.1.3 The operating procedures of the equipment shall be specified. These operating
procedures shall include but are not limited to:
a) Step-by-step operating instructions;
b) Fault conditions, fault indications and conditioning measures;
c) Maintenance and calibration instructions;
d) Technical support contact information.
9.2.2 Qualification
9.2.2.1 The installation of equipment and all associated services shall be in accordance
with the architectural and engineering drawings.
9.2.2.2 Installation instructions shall be documented and shall include instructions
relevant to the health and safety of personnel.
9.2.2.3 Conditions for the safe storage of ethylene oxide shall be specified to ensure
that its quality and composition remain within the specified requirements.
9.2.2.4 The calibration status of test instruments used during installation qualification
shall be determined before the installation qualification is performed.
9.2.2.5 During the installation appraisal, drawings of the installation equipment,
pipelines and other ancillary equipment shall be completed.
9.2.2.6 The impact of system changes during installation qualification on design and
process specifications shall be evaluated and recorded in the design history file.
9.3 Operational qualification
9.3.1 Prior to operational qualification, the calibration status of all instruments
(including test instruments) used to monitor, control, indicate or record the sterilization
process shall be determined (see 4.3.3).
9.3.2 Operational qualification shall demonstrate that the installed equipment meets its
operating specifications.
9.4 Performance qualification
9.4.1 General
9.4.1.1 Performance qualification consists of microbiological performance
9.4.2.1 Microbiological performance qualification shall demonstrate that the
application of the sterilization process meets the specified sterility requirements. This
qualification shall be carried out in a production sterilizer using set process parameters
that have a lower lethality than the specified sterilization process parameters.
9.4.2.2 Microbiological performance qualification shall determine the effectiveness of
the established process for the product/load combination in the production sterilizer.
9.4.2.3 The kill rate of a sterilization cycle shall be determined using the method
described in Annex A or Annex B, or an alternative method that has been validated and
demonstrated to achieve the required sterility assurance level.
9.4.2.4 If the process definition is established in a development sterilizer, the
microbiological performance qualification shall be run in a production sterilizer for at
least three fractional cycles or half cycles to confirm the data from the development
sterilizer.
9.4.2.5 If the overkill half-cycle method [see B.1.2a)] is used, there shall be no positive
internal process challenge devices during the half-cycle operation.
If the external process challenge device has been demonstrated to be more resistant than
the internal process challenge device that provides the “worst case challenge” for
routine processing, an external process challenge device that is positive at half the cycle
is acceptable. The internal process challenge device shall be completely negative.
9.4.2.6 If the overkill cycle calculation method [see B.1.2b)] or the biological
indicator/bioburden method (see Annex A) is used, positive internal process challenge
devices are allowed to exist, but the calculated sterility assurance level shall meet the
specified value (see GB/T 19972-2018).
9.4.3 Performance qualification - Physical
9.4.3.1 Physical property qualification shall demonstrate:
a) The entire load meets the acceptance criteria set forth in the proposed routine
process specification;
b) Process reproducibility.
At least three consecutive, planned qualification runs shall be included. These runs shall
meet all specified acceptance criteria. Physical performance qualification may be
performed during the microbiological performance qualification. If physical
performance qualification is performed simultaneously with at least three
microbiological performance qualifications, at least one additional physical
performance qualification using routine parameters for the full cycle shall be performed.
If the cause of the failure is not related to the process effectiveness factor being verified,
it can be recorded as not related to process performance. No additional three
consecutive successful runs are required. Such types of failures include, but are not
limited to, power outages, loss of other supplied services, or failure of external
monitoring equipment.
9.4.3.2 Physical performance identification shall determine the following process:
a) The minimum temperature of the product entering the sterilization process and/or
the conditions required to achieve the minimum temperature shall be established;
b) At the end of the set preconditioning time (if used), the temperature and humidity
of the sterilization load shall be established;
c) A specified maximum time interval between the end of preconditioning (if used)
and the start of the sterilization cycle is appropriate;
d) At the end of the set conditioning time (if used), the temperature and humidity of
the sterilization load shall be established;
e) If parameter release is adopted, the humidity of the chamber room shall be
recorded;
f) Gaseous ethylene oxide has entered the sterilizer;
g) The pressure rise and the amount of ethylene oxide used or the ethylene oxide
concentration in the sterilizer shall be established [see 9.5.4f)]. If parametric
release is used, see 9.5.5b);
h) During the sterilization cycle, the sterilizer temperature, humidity (if recorded)
and other applicable process parameters shall be established;
i) The product loading temperature during exposure shall be established;
j) During aeration (if used), the sterile loading temperature shall be established.
9.5 Review and approval of validation
9.5.1 The objective of this chapter is to review and document validation data to
determine conformity with the approved sterilization process procedures/protocols and
to approve process specifications.
9.5.2 Information collected or generated during product definition, process definition,
installation qualification, operational qualification and performance qualification,
including the results of biological indicator culture, shall be recorded and reviewed for
acceptability. The results of the review shall be recorded.
9.5.3 A confirmation report shall be prepared and reviewed and approved by the
designated responsible person.
9.5.4 The validation report shall describe or reference the specific validated product,
......
Source: Above contents are excerpted from the PDF -- translated/reviewed by: www.chinesestandard.net / Wayne Zheng et al.
|