INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USEICH Harmonised Tripartite GuidelineGood Manufacturing Practice Guide forActive Pharmaceutical IngredientsQ7Current Step 4 versiondated 10 November 2000This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA.Q7Document HistoryFirst CodificationHistoryDateNew CodificationNovember 2005Q7AApproval by the Steering Committee under Step 2 and release for public consultation.19July2000Q7Current Step 4 versionQ7AApproval by the Steering Committee under Step 4 and recommendation for adoption to the three ICH regulatory bodies.10 November 2000Q7Good Manufacturing Practice Guide forActive Pharmaceutical IngredientsICH Harmonised Tripartite GuidelineHaving reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 10 November 2000, this guideline is recommended for adoption to the three regulatory parties to ICHTABLE OF CONTENTS1. INTRODUCTION 11.1 Objective 11.2 Regulatory Applicability 11.3 Scope 12. QUALITY MANAGEMENT 42.1 Principles 42.2 Responsibilities of the Quality Unit(s) 42.3 Responsibility for Production Activities 52.4 Internal Audits (Self Inspection) 52.5 Product Quality Review 63. PERSONNEL 63.1 Personnel Qualifications 63.2 Personnel Hygiene 63.3 Consultants 74. BUILDINGS AND FACILITIES 74.1 Design and Construction 74.2 Utilities 84.3 Water 84.4 Containment 84.5 Lighting 94.6 Sewage and Refuse 94.7 Sanitation and Maintenance 95. PROCESS EQUIPMENT 95.1 Design and Construction 95.2 Equipment Maintenance and Cleaning 105.3 Calibration 115.4 Computerized Systems 116. DOCUMENTATION AND RECORDS 126.1 Documentation System and Specifications 126.2 Equipment Cleaning and Use Record 126.3 Records of Raw Materials, Intermediates, API Labelling and Packaging Materials 136.4 Master Production Instructions (Master Production and Control Records) 136.5 Batch Production Records (Batch Production and Control Records) 146.6 Laboratory Control Records 146.7 Batch Production Record Review 157. MATERIALS MANAGEMENT 167.1 General Controls 167.2 Receipt and Quarantine 167.3 Sampling and Testing of Incoming Production Materials 167.4 Storage 177.5 Re-evaluation 178. PRODUCTION AND IN-PROCESS CONTROLS 188.1 Production Operations 188.2 Time Limits 188.3 In-process Sampling and Controls 188.4 Blending Batches of Intermediates or APIs 198.5 Contamination Control 209. PACKAGING AND IDENTIFICATION LABELLING OF APIS AND INTERMEDIATES 209.1 General 209.2 Packaging Materials 209.3 Label Issuance and Control 209.4 Packaging and Labelling Operations 2110. STORAGE AND DISTRIBUTION 2210.1 Warehousing Procedures 2210.2 Distribution Procedures 2211. LABORATORY CONTROLS 2211.1 General Controls 2211.2 Testing of Intermediates and APIs 2311.3 Validation of Analytical Procedures - see Section 12. 2411.4 Certificates of Analysis 2411.5 Stability Monitoring of APIs 2411.6 Expiry and Retest Dating 2511.7 Reserve/Retention Samples 2512. VALIDATION 2512.1 Validation Policy 2512.2 Validation Documentation 2612.3 Qualification 2612.4 Approaches to Process Validation 2612.5 Process Validation Program 2712.6 Periodic Review of Validated Systems 2712.7 Cleaning Validation 2812.8 Validation of Analytical Methods 2813. CHANGE CONTROL 2914. REJECTION AND RE-USE OF MATERIALS 2914.1 Rejection 2914.2 Reprocessing 3014.3 Reworking 3014.4 Recovery of Materials and Solvents 3014.5 Returns 3115. COMPLAINTS AND RECALLS 3116. CONTRACT MANUFACTURERS (INCLUDING LABORATORIES) 3117. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 3217.1 Applicability 3217.2 Traceability of Distributed APIs and Intermediates 3217.3 Quality Management 3317.4 Repackaging, Relabelling and Holding of APIs and Intermediates 3317.5 Stability 3317.6 Transfer of Information 3317.7 Handling of Complaints and Recalls 3317.8 Handling of Returns 3418. SPECIFIC GUIDANCE FOR APIS MANUFACTURED BY CELL CULTURE/FERMENTATION 3418.1 General 3418.2 Cell Bank Maintenance and Record Keeping 3518.3 Cell Culture/Fermentation 3518.4 Harvesting, Isolation and Purification 3618.5 Viral Removal/Inactivation steps 3619. APIS FOR USE IN CLINICAL TRIALS 3719.1 General 3719.2 Quality 3719.3 Equipment and Facilities 3719.4 Control of Raw Materials 3719.5 Production 3819.6 Validation 3819.7 Changes 3819.8 Laboratory Controls 3819.9 Documentation 3820. GLOSSARY 39Good Manufacturing Practice Guide forActiv。