PDA-TR49-生物清洁验证（中英文翻译）.docx

Points to Consider for Biotechnology Cleaning Validation Technical Report No. 49 ISBN: 978-0-939459-30-8 ? 2010 Parenteral Drug Association, Inc. All rights reserved. Page 1 of 95 1.0 INTRoduCTIoN 3 1.1 Purpose/Scope 3 2.0 GlossaRy oF TeRms 5 CleaNING PRoCess desIGN aNd deVeloPmeNT 6 Introduction 6 Cleaning Process Controls (Inputs) and Measurements (Outputs) 6 Cleaning Cycle Design 6 Physical-Chemical Aspects 7 Measurements Used to Determine Cleaning Effectiveness 8 Equipment and Plant Design Considerations 8 Piping 8 Automated vs. Manual Systems 9 Centralized CIP vs. Discrete Cleaning of Isolated Equipment 9 Clean Out of Place (COP) 9 Soil Evaluation and Categorization 9 Soil Categories 9 Soil Removal 10 Cleaning Comparability Based on Soil and Surface 11 Soil Selection for Laboratory Evaluations 12 Performing Cleaning Development Experiments 12 Parameter Selection 13 Parameter Interactions 13 Cleaning Process Scale-Up 13 Setting Process Controls 14 Introduction of New Soils to a Validated Cleaning System 14 Applying the “Design Space” Concept to Cleaning Processes 15 0 aCCePTaNCe lImITs 17 Key Issues in Limits for Actives 17 Establishing Limits for Actives in Formulation and Final Fill 18 Establishing Limits for Actives in Bulk Manufacture 18 Limits Based on Toxicity Data 19 Limits for Cleaning Agents 20 Limits for Commodity Chemicals 20 Limits for Formulated Cleaning Agents 20 Bioburden Limits 21 Endotoxin Limits 21 Visual Clean Criterion 21 Modifying Limits 22 samPlING meThods 23 Sampling Method Selection 23 Direct Sampling Methods 23 Rinse Sampling 23 Swab Sampling 24 Comparison of Swab and Rinse Sampling 25 Placebo Sampling 26 Sampling for Microbial and Endotoxin Analysis 26 Sampling Recovery Studies 26 General Considerations 26 Swab Recovery 27 Rinse Recovery 27 “Recovery” in Visual Inspection 28 Recovery for Bioburden and Endotoxin Sampling 28 Training and Qualification of Samplers 29 Key Issues for Training for Swab Sampling 29 Key Issues for Training fo