08/30149503 DC : DRAFT JAN 2008

Foreword
Introduction
1 Scope
2 Normative references
3 Terms and definitions
4 General
5 Characteristics of biological indicators
   5.1 General
   5.2 Test organism suspension for direct inoculation
        of products
   5.3 Inoculated carriers
   5.4 Self-contained biological indicators
   5.5 Other biological indicators
6 Selection of supplier
   6.1 General
   6.2 Documentation
        6.2.1 General
        6.2.2 Manufacturer audit
7 Biological indicators in process development
   7.1 General
   7.2 Overkill approach
   7.3 Combined biological indicator and bioburden method
   7.4 Bioburden method
8 Biological indicators in sterilization validation
   8.1 General
   8.2 Placement and handling of biological indicators
   8.3 Sterilizer qualification
   8.4 Performance qualification
   8.5 Review and approval of validation
   8.6 Requalification
9 Biological indicators in routine monitoring
   9.1 General
   9.2 Placement and handling of biological indicators
   9.3 Process challenge device (PCD)
10 Results
   10.1 General
   10.2 Interpretation of results
11 Application of biological indicator standards
   11.1 General assessment of biological indicator
        performance by the user
   11.2 Nominal population of test organism
   11.3 Resistance determination
        11.3.1 General
        11.3.2 Survivor curve method
        11.3.3 Fraction-negative method
   11.4 z-value determination
        11.4.1 General
        11.4.2 Graphically plotting the z-value
        11.4.3 Mathematically calculating the z-value
        11.4.4 Correlation coefficient (r) for the z-value
   11.5 F (T, Z) Equivalent sterilization value determination
   11.6 Establishing spore-log-reduction (SLR)
   11.7 Sterility assurance level (SAL) calculation
   11.8 Testing equipment
12 Culture conditions
   12.1 General
   12.2 Incubation temperature
   12.3 Incubation period
   12.4 Choice of growth medium
13 Third-party requirements
   13.1 General
   13.2 Minimum requirements for replicates and total
        number of biological indicators
   13.3 Test equipment
14 Personnel train
15 Storage and handling
15 Storage and handling
16 Disposal of biological indicators
Annex A (informative) - Microbiological inactivation kinetics
        and enumeration techniques
Annex B (informative) - Process challenge devices
  B.1 General
  B.2 Helices
  B.3 Standard test packs
  B.4 User's process challenge devices
  B.5 Biological test packs
Annex C (informative) - Formulae for fraction negative methods
        for D-value calculations
  C.1 General
  C.2 Materials
  C.3 Methods
      C.3.1 Holcomb-Spearman-Karber Procedure (HSKP)
      C.3.2 Limited Holcomb-Spearman-Karber-Procedure (LHSKP)
      C.3.3 The Stumbo-Murphy-Cochran-Procedure (SMCP)
Annex D (informative) - Examples of documentation for biological
        indicators prepared by the user
  D.1 General
      D.1.1 Sources of microorganism
      D.1.2 Documentation
  D.2 Commercially available suspension
  D.3 Suspension from a commercially available strain
  D.4 Suspension from in-house isolates
  D.5 Inoculated carriers
      D.5.1 General
      D.5.2 Documentation of fluid carrier materials
      D.5.3 Documentation of solid carrier materials
      D.5.4 Documentation of inoculated carriers used for
Annex E (informative) - Calculation of z-value
Annex F (informative) - D-value determination by survivor
        curve method
  F.1 General
  F.2 Materials
  F.3 Procedure
Bibliography

BS EN ISO 14161