Validation of aseptic process

PHARMACEUTICAL INSPECTION CONVENTION PHARMACEUTICAL INSPECTION CO-OPERATION SCHEME

PI 007-1 31 July 2001

RECOMMENDATION on the

VALIDATION OF ASEPTIC PROCESSES

© PIC/S July 2001 Reproduction prohibited for commercial purposes. Reproduction for internal use is authorised, provided that the source is acknowledged.

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31 July 2001

PI 007-1

TABLE OF CONTENTS Page 1. 2. 2.1 2.2 2.3 3. 4. 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 5. 5.1 5.2 5.3 5.4 5.5 6. 7. 7.1 7.2 7.3 7.4 8. DOCUMENT HISTORY ...........................................................1 INTRODUCTION....................................................................1 Purpose .................................................................................1 Scope ....................................................................................1 General information................................................................1 DEFINITIONS ........................................................................3 PROCESS SIMULATIONTEST PROCEDURES ......................4 General Comments ................................................................4 Liquid Products ......................................................................5 Injectable Powder Products ....................................................6 Suspension Products..............................................................6 Freeze Dried(Lyophilised) Products .......................................6 Semi-Solid Products (e.g. sterile ointments) ............................6 Clinical Trials Materials and Small Batch Size Products...........7 Biological and Biotechnology Products....................................7 Sterile Bulk Pharmaceuticals ..................................................7 PROCESS SIMULATION TEST CONDITIONS........................7 Test Performance...................................................................7 Selection of Growth Medium ...................................................8 Incubation Conditions .............................................................9 Reading of the Test ................................................................9 Test Frequency......................................................................9 INTERPRETATION OF DATA ...............................................10 ENVIRONMENTAL AND PERSONNEL MONITORING...........12 Air Borne Microbial and Non-Viable Particle Monitoring .........12 Non-viable monitoring...........................................................13 Microbial Monitoring .............................................................13Intervention Monitoring .........................................................13 STAFF TRAINING ................................................................14

31 July 2001

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PI 007-1

Page 9. 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 9.9 10. IMPORTANT FACTORS IN VALIDATION OF ASEPTIC MANUFACTURING ..............................................................15 Container/Closure IntegrityTesting .......................................15 Container/Closure Sterilisation .............................................15 Equipment Cleaning and Sterilisation....................................15 Disinfection ..........................................................................16 Filter Validation ....................................................................17 Vent Filters..........................................................................17 Equipment Maintenance and Testing ....................................17 Blow Fill Seal/Form Fill Seal .................................................18 Sterility Test.........................................................................18 REVISION HISTORY ............................................................19...