GuidanceforIndustry-FoodandDrugAdministration.docVIP

Sterile Drug Products Produced by Aseptic Processing Draft TABLE OF CONTENTS Draft 1 I. Introduction 1 II. Background 1 III. Scope 2 IV. BUILDINGS AND FACILITIES 2 A. Critical Area (Class 100) 3 B. Supporting Clean Areas 4 C. Clean Area Separation 5 D. Air Filtration 5 1. Membrane (Compressed Gases) 5 2. High Efficiency Particulate Air (HEPA) 6 E. Design 7 V. PERSONNEL TRAINING, QUALIFICATION, MONITORING 9 A. Manufacturing Personnel 10 B. Laboratory Personnel 12 C. Monitoring Program 12 VI. COMPONENTS AND CONTAINER/CLOSURES 12 A. Components 12 B. Containers/Closures 13 1. Preparation 14 2. Inspection of Container-Closure System 15 VII. ENDOTOXIN CONTROL 15 VIII. TIME LIMITATIONS 16 IX. PROCESS VALIDATION AND EQUIPMENT QUALIFICATION 17 A. Process Simulations 17 1. Study Design 18 2. Frequency and number of runs 18 3. Size and Duration of runs 19 4. Line Speed 20 5. Environmental Conditions 20 6. Media 20 7. Incubation and Examination of Media Filled Units 21 8. Interpretation of Test Results 22 B. Filtration Efficacy 23 C. Sterilization of Equipment and Container/Closures 24 1. Sterilizer Qualification and Validation 25 2. Equipment Controls and Instrument Calibration 26 X. LABORATORY CONTROLS 27 A. Environmental Monitoring 27 1. General Written Program 27 2. Establishing Limits and a Trending Program 28 3. Sanitization Efficacy 29 4. Monitoring Methods 29 B. Microbiological Media and Identification 30 C. Pre-filtration Bioburden 31 D. Particulate Monitoring 31 XI. STERILITY TESTING 31 A. Choice of Methods 32 B. Media 32 C. Personnel 33 D. Sampling and Incubation 33 E. Investigation of Sterility Positives 33 XII. BATCH RECORD REVIEW: PROCESS CONTROL DOCUMENTATION 36 APPENDIX 1: ASEPTIC PROCESSING ISOLATORS 37 A) Maintenance 37 1. General 37 2. Glove Integrity 37 B) Design 37 1. Airflow 37 2. Materials of Construction 38 3. Pressure Differential 38 4. Clean Area Classifications 38 C) Transfer of Materials/Supplies 38 1. Int