GB 18280.1-2015Sterilization of health care products -- Radiation -- Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices (English PDF)

1.2.1 This document does not specify requirements for medical devices to be designated

“STERILE”.

NOTE. For China’s requirements for designating medical devices as “STERILE”, refer to YY/T

0615.1.

1.2.2 This document does not specify a quality management system for controlling all stages of the medical device manufacturing process.

NOTE. This document does not require the establishment of a complete quality management system in manufacturing, but the elements that need to be controlled in the sterilization process within the quality management system shall refer to the applicable clauses in this document (see Clause 4). The application of the reference quality management system standard (see GB/T 42061) in the entire medical device manufacturing process, including sterilization, is permitted.

1.2.3 This document does not require the use of biological indicators in the validation and monitoring of radiation sterilization, nor does it require the use of products listed in the pharmacopoeia for test for sterility and release.

1.2.4 This document does not specify occupational safety requirements related to the design

and operation of irradiation plants.

NOTE. For Chinese occupational safety regulations related to radiation, refer to GB 10252, GB

18871, and HJ 979.

1.2.5 This document does not specify sterilization requirements for used and reprocessed

medical devices.

3.1 Dose

Absorbed Dose

The energy of ionizing radiation transmitted to a unit mass of a substance.

NOTE. The unit of absorbed dose is Gray (Gy), 1 Gy=1 J/kg (=100 rad).

[Source. ISO 11139.2018, 3.3, with modifications]

3.2 Bioburden

The total number of microorganisms surviving on or inside the surface of a product and/or a sterile barrier system.

[Source. ISO 11139.2018, 3.23]

3.3 Biological Indicator

[Source. ISO 11139.2018, 3.315]

4.2 Calibration procedures for all equipment (including instruments used for testing purposes)

used to meet the requirements of this document shall be specified.

4.3 Dosimetry used for the development, validation and routine control of a sterilization process shall be traceable to national or international standards and shall have a known level of uncertainty.

NOTE. Dosimetry procedures are described in ISO/ASTM 52628.

5.1 Sterilizing Agent

5.1.1 The type of radiation used in the sterilization processing (e.g., gamma rays, electron beams, or X-rays) shall be specified.

5.1.2 For electron beams or X-rays, the energy level of the electron beam shall be specified.

The potential for induced radioactivity in the product and packaging system shall be assessed if any of the following conditions exist.

--- The electron energy level exceeds 11 MeV;

--- The electron energy level used to generate X-rays exceeds 7.5 MeV.

The results of the assessment and the basis for the decisions shall be documented.

NOTE. Further guidance is available in Appendix A.

5.2 Inactivation Efficacy

The application of radiation in the inactivation of microorganisms or in the sterilization processing is well documented in the literature. The aforementioned literature provides knowledge of how process variables affect microbial inactivation. This document does not require a comprehensive study involving microbial inactivation.

5.3 Material Effects

The effects of radiation on various materials used in the manufacture of medical devices are well documented, and this literature is valuable for the design and development of medical devices sterilized by radiation. This document does not require a study of the material effects, but it does require a study of the effects of radiation on the product and packaging system (see

8.1).

5.4 Environmental Considerations

An assessment of the potential environmental impacts of the radiation sterilization process shall be conducted, and environmental protection measures shall be developed. This assessment and environmental impact (if any) shall be documented, and control measures (if developed) shall be specified and implemented.

6.1 Processes

Process parameters and their tolerances are part of the process specifications (see 9.4.3), and methods for monitoring and controlling process variables shall be defined. Actions shall be taken to ensure that failure of control functions does not lead to the invalidation of process variable records, so as not to make an invalid process appear valid. This can be achieved by using independent control and monitoring systems, or by identifying any discrepancies characterizing the fault through cross-checking between control and monitoring.

NOTE. For guidance on identifying, monitoring and controlling process variables related to the establishment and control of a radiation sterilization process, refer to ISO/TS 11137-4.

6.2 Equipment

6.2.1 Specify the irradiation facility and its operation methods. Revise the specifications for the irradiation facility as necessary (see 12.5.1) and retain these specifications for the duration of the irradiation facility’s service life (see 4.1).

6.2.2 Software used for controlling or monitoring processes shall be validated.

6.2.3 Table 1 lists the minimum requirements that the equipment design specifications for

and the placement of products within the packaging).

7.2 A production quality management system for the product shall be specified and implemented to ensure that the product’s state and bioburden are controllable when submitted for sterilization and will not jeopardize the effectiveness of the sterilization process. For products that support microbial growth, careful consideration shall be given to controlling microorganisms throughout the period up to the start of sterilization. Factors to consider include the maximum time interval between manufacturing and completion of irradiation, and environmental conditions. The effectiveness of the production system shall be demonstrated, including bioburden determination (with characterization) and bioburden warning and action limits established in accordance with GB/T 19973.1.

7.3 If a sterilization dose is established for a product family, the specific requirements for the product family definition in the standard upon which the dose was established must be met (see

8.2).

NOTE. The standard to be followed is GB/T 18280.2 or ISO 13004.

7.4 If a processing category is used for routine processing purposes, the product’s suitability for that category shall be assessed according to documented standards. The assessment shall include consideration of product-related variables that affect the product’s dose and processing specifications. The results of the assessment shall be documented (see 4.1).

7.5 Changes to the product, product packaging, or the placement of the product within the packaging shall be clearly specified (see 12.5.2).

8.1 Establishing the Maximum Acceptable Dose (Dmax,acc)

8.1.1 A maximum acceptable dose (Dmax,acc) of the product shall be established. If the product is treated with the maximum acceptable dose, the product shall meet its specified functional requirements throughout its specified lifespan.

8.1.2 The basic technical requirements for establishing the maximum acceptable dose shall include.

a) a facility for assessing whether the product and packaging meet acceptance criteria;

b) a product physically representative of routine production within a sterile barrier system;

c) an irradiation facility capable of administering precise and accurate doses relevant to routine processing conditions (see 8.4.1).

8.2 Establishing the Sterilization Dose (Dster)

8.2.1 A sterilization dose (Dster) of the product shall be established.

8.2.2 One of the two methods a) and b) of this article shall be selected to establish the sterilization dose.

a) Obtain and utilize information on bioburden quantity or resistance, or both, to establish the sterilization dose;

NOTE 1.A detailed description of the methods for establishing the sterilization dose and the conditions under which these methods can be used is given in GB/T 18280.2, including

Method 1, Methods 2A and 2B.

b) Select and confirm the sterilization dose; in confirming the sterilization dose, the manufacturer shall provide evidence that the selected sterilization dose meets the specified sterility requirements.

NOTE 2.The VDmaxSD method for confirming the sterilization dose and the conditions under which it can be used are specified in detail in GB/T 18280.2, which specifies the selection of

15 kGy and 25 kGy as sterilization doses; while ISO 13004 specifies in detail the selection of 17.5 kGy, 20 kGy, 22.5 kGy, 27.5 kGy, 30 kGy, 32.5 kGy and 35 kGy as sterilization doses. The selection of dose is only effective for the upper limit of the specified average bioburden. The sterility assurance level (SAL) obtained using these methods is 10-6.

8.2.3 The basic technical requirements for establishing the sterilization dose shall include.

a) a microbiology laboratory capable of performing bioburden determination and characterization in accordance with GB/T 19973.1 and the test of sterility in accordance with GB/T 19973.2;

b) a product microbiologically representative of routine production within a sterile barrier system;

c) an irradiation facility capable of administering precise and accurate doses within the required dose range (see 8.4.2).

NOTE. For guidance on dose aspects in radiation sterilization, refer to GB/T 18280.3.

8.3 Specifying the Maximum Acceptable Dose and Sterilization Dose

The maximum acceptable dose and sterilization dose of the product shall be specified.

8.4 Conversion of Maximum Acceptable Dose, Verification Dose, or Sterilization

Dose Between Different Radiation Sources

8.4.1 Conversion of maximum acceptable dose

When converting the maximum acceptable dose from the radiation source where the initial dose

......