PREN ISO 11137-2 : DRAFT 2009

Foreword
Introduction
1 Scope
2 Normative references
3 Abbreviations, terms and definitions
   3.1 Abbreviations
   3.2 Terms
4 Definition and maintenance of product families
   for dose setting, dose substantiation and
   sterilization dose auditing
   4.1 General
   4.2 Defining product families
   4.3 Designation of product to represent a
        product family for performance of a verification
        dose experiment or sterilization dose audit
        4.3.1 Product to represent a product family
        4.3.2 Master product
        4.3.3 Equivalent product
        4.3.4 Simulated product
   4.4 Maintaining product families
        4.4.1 Periodic review
        4.4.2 Modification to product and/or manufacturing
               process
        4.4.3 Records
   4.5 Effect of failure of establishment of sterilization
        dose or of a sterilization dose audit on product family
5 Selection and testing of product for establishing
   the sterilization dose
   5.1 Nature of product
   5.2 Sample item portion (SIP)
   5.3 Manner of sampling
   5.4 Microbiological testing
   5.5 Irradiation
6 Methods of dose establishment
7 Method 1: dose setting using bioburden information
   7.1 Rationale
   7.2 Procedure for Method 1 for product with an
        average bioburden greater than or equal
        to 1,0 for multiple production batches
        7.2.1 General
        7.2.2 Stage 1: Select SAL and obtain samples of
               product
        7.2.3 Stage 2: Determine average bioburden
        7.2.4 Stage 3: Obtain verification dose
        7.2.5 Stage 4: Perform verification dose experiment
        7.2.6 Stage 5: Interpretation of results
        7.2.7 Stage 6: Establish sterilization dose
   7.3 Procedure for Method 1 for product with an average
        bioburden greater than or equal to 1,0 for a single
        production batch
        7.3.1 Rationale
        7.3.2 General
        7.3.3 Stage 1: Select SAL and obtain samples of
               product
        7.3.4 Stage 2: Determine average bioburden
        7.3.5 Stage 3: Obtain verification dose
        7.3.6 Stage 4: Perform verification dose experiment
        7.3.7 Stage 5: Interpretation of results
        7.3.8 Stage 6: Establish sterilization dose
   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
8 Method 2: Dose setting using fraction positive information
   from incremental dosing to determine an extrapolation factor
   8.1 Rationale
   8.2 Procedure for Method 2A
        8.2.1 General
        8.2.2 Stage 1: Select SAL and obtain samples of product
        8.2.3 Stage 2: Perform incremental dose experiment
        8.2.4 Stage 3: Perform verification dose experiment
        8.2.5 Stage 4: Consideration of results
        8.2.6 Stage 5: Establish sterilization dose
   8.3 Procedure for Method 2B
        8.3.1 General
        8.3.2 Stage 1: Select SAL and obtain samples of product
        8.3.3 Stage 2: Perform incremental dose experiment
        8.3.4 Stage 3: Perform verification dose experiment
        8.3.5 Stage 4: Consideration of results
        8.3.6 Stage 5: Establish sterilization dose
9 Method VD[max] - Substantiation of 25 kGy or 15 kGy as
   the sterilization dose
   9.1 Rationale
   9.2 Procedure for Method VD[max][25] for multiple production
        batches
        9.2.1 General
        9.2.2 Stage 1: Obtain samples of product
        9.2.3 Stage 2: Determine average bioburden
        9.2.4 Stage 3: Obtain VD[max][25]
        9.2.5 Stage 4: Perform verification dose experiment
        9.2.6 Stage 5: Interpretation of results
        9.2.7 Confirmatory verification dose experiment
   9.3 Procedure for Method VD[max][25] for a single
        production batch
        9.3.1 Rationale
        9.3.2 General
        9.3.3 Stage 1: Obtain samples of product
        9.3.4 Stage 2: Determine average bioburden
        9.3.5 Stage 3: Obtain VD[max][25]
        9.3.6 Stage 4: Perform verification dose experiment
        9.3.7 Stage 5: Interpretation of results
        9.3.8 Confirmatory verification dose experiment
   9.4 Procedure for Method VD[max][15] for multiple
        production batches
        9.4.1 General
        9.4.2 Stage 1: Obtain samples of product
        9.4.3 Stage 2: Determine average bioburden
        9.4.4 Stage 3: Obtain VD[max][15]
        9.4.5 Stage 4: Perform verification dose experiment
        9.4.6 Stage 5: Interpretation of results
        9.4.7 Confirmatory verification dose experiment
   9.5 Procedure for Method VD[max][15] for a single
        production batch
        9.5.1 Rationale
        9.5.2 General
        9.5.3 Stage 1: Obtain samples of product
        9.5.4 Stage 2: Determine average bioburden
        9.5.5 Stage 3: Obtain VD[max][15]
        9.5.6 Stage 4: Perform verification dose experiment
        9.5.7 Stage 5: Interpretation of results
        9.5.8 Confirmatory verification dose experiment
10 Auditing sterilization dose
   10.1 Purpose and frequency
   10.2 Procedure for auditing a sterilization dose
        established using Method 1 or Method 2
        10.2.1 General
        10.2.2 Stage 1: Obtain samples of product
        10.2.3 Stage 2: Determine average bioburden
        10.2.4 Stage 3: Perform verification dose experiment
        10.2.5 Stage 4: Interpretation of results
        10.2.6 Augmentation of a sterilization dose established
               using Method 1, Method 2A or Method 2B
   10.3 Procedure for auditing a sterilization dose
        substantiated using Method VD[max][25] or VD[max][15]
        10.3.1 General
        10.3.2 Stage 1: Obtain samples of product
        10.3.3 Stage 2: Determine average bioburden
        10.3.4 Stage 3: Perform verification dose experiment
        10.3.5 Stage 4: Interpretation of results
        10.3.6 Confirmatory sterilization dose audit
        10.3.7 Augmentation of a sterilization dose
               substantiated using Method VD[max][25] or
               VD[max][15]
   10.4 Failure of the sterilization dose audit
11 Worked examples
   11.1 Worked examples for Method 1
   11.2 Worked examples for Method 2
        11.2.1 General
        11.2.2 Worked example for Method 2A (SIP equal
               to 1,0)
        11.2.3 Worked example for Method 2A (SIP less
               than 1,0)
        11.2.4 Worked example for Method 2B
   11.3 Worked examples for Method VD[max]
   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
   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
   11.6 Worked example of a sterilization dose audit for
        a sterilization dose substantiated using Method
        VD[max][25]
Annex ZA (informative) - Relationship between this International
         Standard and the Essential Requirements of EU
         Directive 93/42/EEC and 90/385/EEC
Bibliography

Defines 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].