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Table of Contents 1.0 Introduction....................................................2 1.1 Purpose/Scope.................................................2 2.0 Glossary OF TERMS..........................................3 3.0 HOW FILTERS WORK............................................7 3.1 Pore Size Rating...............................................7 4.0 FILTER SELECTION AND CHARACTERIZATION...8 4.1 Filter Qualification and Validation.....................8 4.1.1 Revalidation..............................................9 4.2 Filter Cleanliness..............................................9 4.3 Filter Safety....................................................10 4.3.1 Toxicity....................................................10 4.3.2 Animal-Derived Materials........................10 4.4 Operational Ranges........................................10 4.5 Filter Interactions with the Process Stream..... 10 4.5.1 Evaluating Filter Extractables and Leachables..............................................10 4.5.2 Chemical Compatibility...........................12 4.5.3 Adsorption..............................................12 5.0 Filter Use, Handling and Design Considerations..............................................13 5.1 Flow Characteristics.........................................13 5.2 Filter Throughput...............................................14 5.3 Filter Scale-up Considerations..........................15 5.3.1 Small-Scale Device Testing.......................16 5.3.2 Filter Cartridge Design...............................16 5.4 Effect of System Design...................................17 5.5 Operating Conditions........................................18 5.5.1 Inlet and Differential Pressure....................18 5.5.2. Filtration Process Temperature..................18 5.5.3 Filtration Time (Duration)...........................19 5.5.4 Flushing Conditions / Filter Priming...........19 6.0 STERILIZING FILTER VALIDATION/ BACTERIAL RETENTION.....................................20 6.1 Factors Influencing Bacterial Retention..........20 6.2 Bacterial Retention Validation Studies..............20 6.3 Bacterial Retention Validation Studies – Risk Assessment...........................................21 6.4 Challenge Organism Selection Criteria...........22 6.5 Culture Maintenance and Challenge Preparation.....................................................22 6.6 Testing Procedure and Protocol Development...23 6.7 Nonbactericidal Processes and Fluids............23 6.8 Bacteriostatic/Bactericidal/Nondispersive Challenge Fluids.............................................23 6.8.1 Reduced Exposure Time..........................25 6.8.2 Modify Test Method Parameters.............25 6.8.3 Modify Test Product Formulation............25 6.8.4 Use of Resistant Indigenous Bioburden.....25 6.9 Filtrate Sampling............................................26 6.10 Results Interpretation.....................................26 6.11 Filters in Series..............................................26 6.12 Filter Assembly Change.................................26 7.0 INTEGRITY TESTING............................................27 7.1 Relationship between Integrity Test Results and Bacterial Retention..................................28 7.1.1 Validation Testing....................................29 7.1.2 Integrity Testing of Production Filters......30 7.1.3 Filtrate Sterility Assurance......................30 7.2 Product-Wetted Integrity Tests......................30 7.2.1 Product-Wetted Bubble Point Tests.........30 7.2.1.1 Bubble Point Ratio Approach...........30 7.2.1.2 Bubble Point Statistical Approach...31 7.2.2 Product-Wetted Diffusive/Forward-Flow Test.........................................................32 7.3 Automated Integrity Test Instruments............32 7.4 Integrity Testing of Filters in Large, Multiple-Cartridge Housings..........................33 7.5 Qualification of Integrity Test Devices............33 www.pda.org/bookstore
Table of Contents 7.6 When a Sterilizing-Grade Filter Should be Integrity Tested..............................................34 7.6.1 Pre-Use Integrity Test Considerations.....35 7.6.2 Post-Filtration Integrity Test Considerations........................................36 7.6.3 Serial Filtration........................................36 7.7 Failure Analysis/Troubleshooting....................36 7.7.1 Insufficient Wetting Failure Analysis.......39 8.0 STERILIZATION OF FILTERS...............................40 8.1 Steam Sterilization.........................................40 8.1.1 Autoclave................................................40 8.1.2 Steam in Place........................................41 8.2 Irradiation Sterilization...................................41 8.3 Gas Sterilization.............................................41 8.4 Resterilization of Filters..................................42 9.0 SINGLE-USE DISPOSABLE SYSTEMS................43 9.1 Filter Capsules...............................................43 9.2 User Requirement Specifications...................43 9.3 Component and System Qualification............44 9.3.1 Qualification Tests...................................44 9.3.2 Process and Functionality Tests..............44 10.0 APPENDICES.......................................................46 Appendix A: Diffusive Flow Theory......................46 Appendix B: Nondestructive Physical Integrity Test Methods...................................48 Appendix C: Statistical Adjustment To The Calculated Product-Wetted Bubble Point....................................55 Appendix D: Integrity Test Troubleshooting Guide...56 11.0 REFERENCES.......................................................58 www.pda.org/bookstore
Page 1 and 2: Technical Report No. 26 Revised 200
Page 3: Sterilizing Filtration of Liquids T
Page 7 and 8: 2.0 Glossary of Terms For the purpo
Page 9 and 10: Medium In filtration, the porous ma

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