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CHAPTER 7


              Risk to the patient—Quantifying

              assurance of sterility


                           a
                                                                      a
                                                  b
              Marc L. Speck , Harry Frederick Bushar , James Niederecker ,
              Byron J. Lambert c
              a R&D Quality, Abbott Vascular, Temecula, CA, United States
              b Retired Statistician, Rockville, MD, United States
              c Assurance of Sterility Task Force, ASTF, Abbott, Temecula, CA, United States
              Contents

              7.1  Risk concepts applied to sterility assurance             167
              7.2  Statistical concepts applied to sterility assurance      169
                 7.2.1  Point estimates                                     170
                 7.2.2  Confidence interval example                         171
                 7.2.3  Confidence bounds                                   175
                 7.2.4  Statistical analysis types                          176
              7.3  Statistical analysis of risk associated with packaging and sterilization    179
                 7.3.1  Introduction to scenarios analyzed                  179
                 7.3.2  Point estimates and confidence bounds—Packaging     179
                 7.3.3  Point estimates and confidence bounds—Aseptic processing    182
                 7.3.4  Point estimates and confidence bounds—Terminal sterilization;
                     bioburden-based approach                               186
                 7.3.5  Point estimates and confidence bounds—Terminal sterilization;
                     overkill method                                        191
                 7.3.6  Summary of statistical analysis                     194
              7.4  Relative patient risks from various industry sectors compared to
                 real-world infection rates                                 196
                 7.4.1  Estimates of infection probabilities                196
                 7.4.2  Other factors influencing the assurance of sterility    202
                 7.4.3  Comparison to real-world infection rates            204
              7.5  Risk acceptability—Bringing it all together, the real risk to the patients    205
              7.6  Conclusion                                               207
              References                                                    208


              This chapter provides a novel look at patient risk by quantifying certain
              aspects  of  assurance  of  sterility  related  to packaging, aseptic processing,
                                                                     a
              terminal sterilization, and product use at health-care facilities.  Terminal
              sterilization (Chapter 3) with a validated logarithmic reduction in product

              a
              Note: reprocessed devices are not included in the analysis of this chapter.
              Assurance of Sterility for Sensitive Combination Products and Materials  © 2020 Elsevier Inc.
              https://doi.org/10.1016/B978-0-12-805082-8.00007-4  All rights reserved.  165
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