Sterilization of health care products – Radiation – Part 2: Establishing the sterilization dose (ISO 11137-2:2012)
Abstract
ISO 11137-2:2013 specifies methods for 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. ISO 11137-2:2013 also specifies methods of sterilization dose audit used to demonstrate the continued effectiveness of the sterilization dose.
ISO 11137-2:2013 defines product families for sterilization dose establishment and sterilization dose audit.
DIN EN ISO 11137-2:2013-09 (E)
Sterilization of health care products – Radiation – Part 2: Establishing the sterilization
dose (ISO 11137-2:2013)
Contents Page
Foreword ………………………………………………………………………………………………………………………………………. 4
Introduction …………………………………………………………………………………………………………………………………… 5
1 Scope …………………………………………………………………………………………………………………………….. 6
2 Normative references …………………………………………………………………………………………………….. 6
3 Terms, definitions, and abbreviated terms ………………………………………………………………………. 6
3.1 Terms and definitions …………………………………………………………………………………………………….. 6
3.2 Abbreviated terms ………………………………………………………………………………………………………….. 8
4 Definition and maintenance of product families for dose setting, dose substantiation,
and sterilization dose auditing ……………………………………………………………………………………….. 9
4.1 General ………………………………………………………………………………………………………………………….. 9
4.2 Defining product families ……………………………………………………………………………………………….. 9
4.3 Designation of product to represent a product family for performance of a verification
dose experiment or sterilization dose audit …………………………………………………………………… 10
4.4 Maintaining product families ………………………………………………………………………………………… 11
4.5 Effect of failure of establishment of sterilization dose or of a sterilization dose audit on a
product family ………………………………………………………………………………………………………………. 12
5 Selection and testing of product for establishing the sterilization dose …………………………. 12
5.1 Nature of product …………………………………………………………………………………………………………. 12
5.2 Sample item portion (SIP) …………………………………………………………………………………………….. 12
5.3 Manner of sampling ……………………………………………………………………………………………………… 14
5.4 Microbiological testing …………………………………………………………………………………………………. 14
5.5 Irradiation …………………………………………………………………………………………………………………….. 14
6 Methods of dose establishment ……………………………………………………………………………………. 14
7 Method 1: dose setting using bioburden information …………………………………………………….. 15
7.1 Rationale ……………………………………………………………………………………………………………………… 15
7.2 Procedure for Method 1 for product with an average bioburden greater than or equal to
1,0 for multiple production batches ………………………………………………………………………………. 16
7.3 Procedure for Method 1 for product with an average bioburden greater than or equal to
1,0 for a single production batch …………………………………………………………………………………… 22
7.4 Procedure for Method 1 for product with an average bioburden in the range 0,1 to 0,9 for
multiple or single production batches …………………………………………………………………………… 24
8 Method 2: Dose setting using fraction positive information from incremental dosing to
determine an extrapolation factor …………………………………………………………………………………. 25
8.1 Rationale ……………………………………………………………………………………………………………………… 25
8.2 Procedure for Method 2A ……………………………………………………………………………………………… 26
8.3 Procedure for Method 2B ……………………………………………………………………………………………… 29
9 Method VDmax — Substantiation of 25 kGy or 15 kGy as the sterilization dose ………………. 33
9.1 Rationale ……………………………………………………………………………………………………………………… 33
9.2 Procedure for Method VDmax 25 for multiple production batches …………………………………. 34
9.3 Procedure for Method VDmax 25 for a single production batch ……………………………………… 39
9.4 Procedure for Method VDmax 15 for multiple production batches …………………………………. 42
9.5 Procedure for Method VDmax 15 for a single production batch …………………………………….. 45
10 Sterilization dose audit ………………………………………………………………………………………………… 48
10.1 Purpose and frequency ………………………………………………………………………………………………… 48
10.2 Procedure for auditing a sterilization dose established using Method 1, Method 2A, or
Method 2B …………………………………………………………………………………………………………………… 48
10.3 Procedure for auditing a sterilization dose substantiated using Method VD max 25 or
Method VD max 15 ……………………………………………………………………………………………………….. 51
10.4 Failure of a sterilization dose audit ………………………………………………………………………………. 57
11 Worked examples ………………………………………………………………………………………………………… 57
11.1 Worked examples for Method 1 ……………………………………………………………………………………. 57
11.2 Worked examples for Method 2 ……………………………………………………………………………………. 59
11.3 Worked examples for Method Vdmax …………………………………………………………………………… 67
11.4 Worked example of a sterilization dose audit for a dose established using Method 1, the
findings from which necessitated augmentation of the sterilization dose ……………………… 69
11.5 Worked example of a sterilization dose audit for a dose established using Method 2A,
the findings from which necessitated augmentation of the sterilization dose ………………… 69
11.6 Worked example of a sterilization dose audit for a sterilization dose substantiated using
Method VDmax 25 ………………………………………………………………………………………………………… 70
Bibliography ……………………………………………………………………………………………………………………………….. 72
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on active implantable medical devices …………. 74
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on medical devices ……………………………………….. 75
Annex ZC (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices …………….. 76