1 Scope
This part of GB 18280 specifies methods of determining the minimum dose needed to achieve a specified requirement for sterility and methods to substantiate the use of 25 kGy or 15 kGy as the sterilization dose to achieve a sterility assurance level, SAL, of 10-6. This part also specifies methods of dose auditing in order to demonstrate the continued effectiveness of the sterilization dose.
This part defines product families for dose establishment and dose auditing.
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 18280.1-2015 Sterilization of Health Care Products — Radiation — Part 1: Requirements for Development, Validation and Routine Control of a Sterilization Process for Medical Devices (ISO 11137-1:2006, IDT)
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
3 Abbreviations, Terms and Definitions
For purposes of this document, the terms and definitions given in GB 18280.1-2015 and the following apply.
3.1 Abbreviations
3.1.1
A
dose to adjust the median ffp dose downwards, to the FFP dose
3.1.2
CD*
number of positive tests of sterility obtained from tests performed individually on 100 product items irradiated in a Method 2 verification dose experiment
3.1.3
d*
dose derived from an incremental dose experiment performed on product items drawn from a given production batch
3.1.4
D*
initial estimate of the dose to provide an SAL of 10-2 for the test items
Note: Generally, it is the median of the 3 d * values derived for a given product.
3.1.5
D**
final estimate of the dose to provide an SAL of 10-2 for the test items, which is used in the calculation of the sterilization dose
3.1.6
DD*
dose delivered in a Method 2 verification dose experiment
3.1.7
DS
estimate of D10 value of microorganisms present on product after exposure to DD*
3.1.8
D value
D10 value
time or dose required to achieve inactivation of 90% of a population of the test microorganism under stated conditions
[ISO/TS 11139:2006]
Note: For the purposes of this document, D10 applies to the radiation dose only and not to time.
3.1.9
first fraction positive dose
ffp
lowest dose of an incremental dose series, applied to product items drawn from a given production batch, at which at least one of the associated 20 tests of sterility is negative
3.1.10
First Fraction Positive dose
FFP
dose at which 19 positives out of the 20 tests of sterility are expected to occur, calculated by subtracting A from the median of 3 ffp doses
3.1.11
First No Positive dose
FNP
estimate of the dose to provide an SAL of 10-2 for the test items, which is used in the calculation of DS
3.1.12
VDmax15
maximal verification dose for a given bioburden, consistent with the attainment of an SAL of 10-6 at a specified sterilization dose of 15 kGy
3.1.13
VDmax25
maximal verification dose for a given bioburden, consistent with the attainment of an SAL of 10-6 at a specified sterilization dose of 25 kGy
3.2 Terms and definitions
3.2.1
batch
defined quantity of product, intended or purported to be uniform in character and quality, which has been produced during a defined cycle of manufacture
[ISO/TS 11139:2006]
3.2.2
bioburden
population of viable microorganisms on or in product and/or sterile barrier system
[ISO/TS 11139:2006]
3.2.3
false positive
test result interpreted as growth arising from the product, or portions thereof, tested when either growth resulted from extraneous microbial contamination or turbidity occurred from interaction between the product, or portions thereof, and the test medium
3.2.4
fraction positive
quotient in which the number of positive tests of sterility is given by the numerator and the number of tests performed is given by the denominator
3.2.5
incremental dose
dose within a series of doses applied to a number of product, or portions thereof, and used in a dose setting method to obtain or confirm the sterilization dose
3.2.6
negative test of sterility
test result for which there is no detectable microbial growth from product, or portion thereof, subjected to a test of sterility
3.2.7
packaging system
combination of the sterile barrier system and protective packaging
[ISO/TS 11139:2006]
3.2.8
positive test of sterility
test result for which there is detectable microbial growth from product, or portion thereof, subjected to a test of sterility
3.2.9
sample item portion; SIP
defined portion of a health care product that is tested
3.2.10
sterile barrier system
minimum package that prevents ingress of microorganisms and allows aseptic presentation of product at the point of use
3.2.11
sterility assurance level; SAL
probability of a single viable microorganism occurring on an item after sterilization
Note: The term sterility assurance level takes a quantitative value, generally 10-6 or 10-3. When applying this quantitative value to assurance of sterility, an SAL of 10-6 has a lower value but provides a greater assurance of sterility than an SAL of 10-3.
3.2.12
sterilization dose audit
exercise undertaken to confirm the appropriateness of an established sterilization dose
3.2.13
verification dose
dose of radiation predicted to give a predetermined SAL L≥10-2 used in establishing the sterilization dose
Foreword II
Introduction IV
1 Scope
2 Normative References
3 Abbreviations, Terms and Definitions
4 Definition and Maintenance of Product Families for Dose Setting, Dose Substantiation and Sterilization Dose Auditing
5 Selection and Testing of Product for Establishing and Verifying the Sterilization dose
6 Methods of Dose Establishment
7 Method 1: Dose Setting Using Bioburden Information
8 Method 2: Dose Setting Using Fraction Positive Information from Incremental Dosing to Determine an Extrapolation Factor
9 Method VDmax — Substantiation of 25 kGy or 15 kGy as the Sterilization Dose
10 Auditing Sterilization Dose
11 Worked Examples
Bibliography
1 Scope
This part of GB 18280 specifies methods of determining the minimum dose needed to achieve a specified requirement for sterility and methods to substantiate the use of 25 kGy or 15 kGy as the sterilization dose to achieve a sterility assurance level, SAL, of 10-6. This part also specifies methods of dose auditing in order to demonstrate the continued effectiveness of the sterilization dose.
This part defines product families for dose establishment and dose auditing.
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 18280.1-2015 Sterilization of Health Care Products — Radiation — Part 1: Requirements for Development, Validation and Routine Control of a Sterilization Process for Medical Devices (ISO 11137-1:2006, IDT)
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
3 Abbreviations, Terms and Definitions
For purposes of this document, the terms and definitions given in GB 18280.1-2015 and the following apply.
3.1 Abbreviations
3.1.1
A
dose to adjust the median ffp dose downwards, to the FFP dose
3.1.2
CD*
number of positive tests of sterility obtained from tests performed individually on 100 product items irradiated in a Method 2 verification dose experiment
3.1.3
d*
dose derived from an incremental dose experiment performed on product items drawn from a given production batch
3.1.4
D*
initial estimate of the dose to provide an SAL of 10-2 for the test items
Note: Generally, it is the median of the 3 d * values derived for a given product.
3.1.5
D**
final estimate of the dose to provide an SAL of 10-2 for the test items, which is used in the calculation of the sterilization dose
3.1.6
DD*
dose delivered in a Method 2 verification dose experiment
3.1.7
DS
estimate of D10 value of microorganisms present on product after exposure to DD*
3.1.8
D value
D10 value
time or dose required to achieve inactivation of 90% of a population of the test microorganism under stated conditions
[ISO/TS 11139:2006]
Note: For the purposes of this document, D10 applies to the radiation dose only and not to time.
3.1.9
first fraction positive dose
ffp
lowest dose of an incremental dose series, applied to product items drawn from a given production batch, at which at least one of the associated 20 tests of sterility is negative
3.1.10
First Fraction Positive dose
FFP
dose at which 19 positives out of the 20 tests of sterility are expected to occur, calculated by subtracting A from the median of 3 ffp doses
3.1.11
First No Positive dose
FNP
estimate of the dose to provide an SAL of 10-2 for the test items, which is used in the calculation of DS
3.1.12
VDmax15
maximal verification dose for a given bioburden, consistent with the attainment of an SAL of 10-6 at a specified sterilization dose of 15 kGy
3.1.13
VDmax25
maximal verification dose for a given bioburden, consistent with the attainment of an SAL of 10-6 at a specified sterilization dose of 25 kGy
3.2 Terms and definitions
3.2.1
batch
defined quantity of product, intended or purported to be uniform in character and quality, which has been produced during a defined cycle of manufacture
[ISO/TS 11139:2006]
3.2.2
bioburden
population of viable microorganisms on or in product and/or sterile barrier system
[ISO/TS 11139:2006]
3.2.3
false positive
test result interpreted as growth arising from the product, or portions thereof, tested when either growth resulted from extraneous microbial contamination or turbidity occurred from interaction between the product, or portions thereof, and the test medium
3.2.4
fraction positive
quotient in which the number of positive tests of sterility is given by the numerator and the number of tests performed is given by the denominator
3.2.5
incremental dose
dose within a series of doses applied to a number of product, or portions thereof, and used in a dose setting method to obtain or confirm the sterilization dose
3.2.6
negative test of sterility
test result for which there is no detectable microbial growth from product, or portion thereof, subjected to a test of sterility
3.2.7
packaging system
combination of the sterile barrier system and protective packaging
[ISO/TS 11139:2006]
3.2.8
positive test of sterility
test result for which there is detectable microbial growth from product, or portion thereof, subjected to a test of sterility
3.2.9
sample item portion; SIP
defined portion of a health care product that is tested
3.2.10
sterile barrier system
minimum package that prevents ingress of microorganisms and allows aseptic presentation of product at the point of use
3.2.11
sterility assurance level; SAL
probability of a single viable microorganism occurring on an item after sterilization
Note: The term sterility assurance level takes a quantitative value, generally 10-6 or 10-3. When applying this quantitative value to assurance of sterility, an SAL of 10-6 has a lower value but provides a greater assurance of sterility than an SAL of 10-3.
3.2.12
sterilization dose audit
exercise undertaken to confirm the appropriateness of an established sterilization dose
3.2.13
verification dose
dose of radiation predicted to give a predetermined SAL L≥10-2 used in establishing the sterilization dose
Contents of GB 18280.2-2015
Foreword II
Introduction IV
1 Scope
2 Normative References
3 Abbreviations, Terms and Definitions
4 Definition and Maintenance of Product Families for Dose Setting, Dose Substantiation and Sterilization Dose Auditing
5 Selection and Testing of Product for Establishing and Verifying the Sterilization dose
6 Methods of Dose Establishment
7 Method 1: Dose Setting Using Bioburden Information
8 Method 2: Dose Setting Using Fraction Positive Information from Incremental Dosing to Determine an Extrapolation Factor
9 Method VDmax — Substantiation of 25 kGy or 15 kGy as the Sterilization Dose
10 Auditing Sterilization Dose
11 Worked Examples
Bibliography
