GOOD MANUFACTURING PRACTICE GUIDELINE FOR …

1 Ethiopian Food, Medicine & Healthcare Administration & Control Authority (EFMHACA) good MANUFACTURING PRACTICE GUIDELINE FOR PHARMACEUTICAL PRODUCTS MAIN PRINCIPLES First Edition, 2014 Addis Ababa, Ethiopia i Table of Contents ACKNOWLEDGMENTS .. viii DEFINITIONS .. 2 CHAPTER ONE-QUALITY 11 Principle .. 11 Quality Assurance .. 11 good MANUFACTURING PRACTICE for Products .. 12 Quality Control .. 12 Product Quality Review .. 13 Quality Risk Management .. 14 CHAPTER TWO- SANITATION AND HYGIENE .. 15 Principle .. 15 General .. 15 CHAPTER THREE-PREMISES.

2 16 Principle .. 16 Premises .. 16 General Requirement .. 16 Production Area .. 16 Storage Area .. 17 Quality Control Area .. 18 Ancillary Area .. 18 Principle .. 19 General Requirement .. 19 CHAPTER 20 Principles .. 20 General .. 20 Starting Materials .. 20 Packaging Materials .. 21 Intermediate and Bulk Products .. 21 Finished Products .. 22 Rejected, Recovered, Reprocessed and Reworked Materials .. 22 Recalled Products .. 22 Returned Products .. 22 ii Reagents and Culture Media .. 22 Reference Standards .. 23 Waste Materials .. 23 Miscellaneous .. 23 CHAPTER SIX-PERSONNEL.

3 24 Principle .. 24 General .. 24 Key Personnel .. 24 26 Personnel Hygiene .. 26 CHAPTER SEVEN-PRODUCTION .. 28 Principle .. 28 General .. 28 Prevention of Cross Contamination in Production .. 29 Validation .. 29 Starting Materials .. 30 Processing Operation-Intermediate and 30 Packaging Operations .. 30 CHAPTER EIGHT-QUALITY 32 Principle .. 32 General .. 32 good Quality Control Laboratory PRACTICE .. 32 Documentation .. 32 Sampling .. 33 Testing .. 33 Stability Study 34 CHAPTER NINE-CONTRACT PRODUCTION AND 37 Principle .. 37 General .. 37 The contract giver.

4 37 The Contract acceptor .. 37 The Contract .. 38 CHAPTER TEN-COMPLAINTS AND PRODUCT RECALL .. 39 Principle .. 39 iii Complaints .. 39 Recall .. 39 CHAPTER ELEVEN- SELF INSPECTION AND QUALITY AUDITS .. 41 Principle .. 41 General .. 41 CHAPTER TWELVE- VALIDATION AND QUALIFCATION .. 42 Principles .. 42 Validation .. 42 Qualification .. 42 Design Qualification .. 42 Installation Qualification .. 43 Operational Qualification .. 43 Performance Qualification .. 43 Process Validation .. 43 General .. 43 Prospective Validation .. 44 Concurrent Validation .. 44 Retrospective Validation.

5 45 Qualification of Established (in use) Facilities, Systems and Equipment .. 45 Cleaning Validation .. 45 Change Control .. 46 Computerized System .. 46 Principle .. 46 General .. 46 System .. 47 Validation .. 48 Hardware Validation .. 49 Analytical Method Validation Principle .. 50 General .. 50 Pharmacopoeial method .. 51 Non-pharmacopoeial method .. 51 Method Validation .. 51 Characteristics of analytical validation .. 51 System Suitability Testing .. 53 iv Revalidation .. 53 CHAPTER THIRTEEN-DOCUMENTATION .. 54 Principle .. 54 General .. 54 Essential Documents Specifications.

6 55 Specifications for starting and packaging materials .. 55 Specifications for intermediate and bulk products .. 55 Specifications for Finished Products .. 55 Batch Formula and Processing Instruction .. 55 Packaging Instructions .. 56 Batch Processing Records .. 56 Batch Packaging Records .. 57 Procedures and Records .. 58 CHAPTER FOURTEEN-WATER FOR PHARMACEUTICAL USE .. 60 Principle .. 60 General .. 60 Water Quality Specification .. 60 Drinking Water .. 61 Purified Water .. 61 Highly Purified Water .. 61 Other Grades of Water .. 61 Application of Specific Water for Dosage Form Processing.

7 62 Water Purification .. 62 General .. 62 Production of Drinking Water .. 63 Production of Purified water .. 63 Production of Highly Purified Water .. 64 Water Storage and Distribution .. 64 General .. 64 Sanitization of Water System .. 66 Storage Vessel .. 66 Water Distribution Pipe .. 67 Temperature Control and Heat Exchangers .. 67 Circulation Pumps .. 67 v Bio-contamination Control System .. 67 Operational Consideration .. 68 CHAPTER FIFTEEN-HEATING, VENTILATION AND AIR CONDITIONING SYSTERM (HVAC) .. 69 Principle .. 69 Scope .. 69 Protection.

8 69 Product and 69 Cross-Contamination .. 72 Temperature and Relative Humidity .. 73 Dust Control .. 74 Protection from the Environment .. 75 Vapour and Fume Removal .. 76 HVAC System and Component .. 77 Principle .. 77 General .. 77 Re-circulation system .. 77 Fresh Air System .. 78 Commissioning, Qualification and maintenance of HVAC system .. 78 ANNEX I-MANUFACTURE OF STERILE MEDICINAL PRODUCTS .. 79 PRINCIPLE .. 79 GENERAL .. 79 Clean Area Classification .. 80 Clean Area Monitoring .. 80 Barrier/Isolator Technology .. 82 Blow/Fill/Seal Technology .. 82 Terminally Sterilized Products.

9 83 Aseptic Preparation .. 83 Personnel .. 84 Premises .. 85 Equipment .. 86 Sanitation .. 86 Processing .. 86 Sterilisation .. 88 vi Sterilisation by Heat .. 89 Sterilisation by Moist Heat .. 89 Sterilisation by Dry Heat .. 90 Sterilisation by Radiation .. 90 Sterilisation with Ethylene Oxide .. 90 Sterilization by Filtration .. 91 Finishing of Sterile Products .. 91 Quality Control .. 92 ANNEX II- MANUFACTURING BIOLOGICAL MEDICINAL PRODUCTS .. 93 SCOPE .. 93 Principle .. 93 Personnel .. 93 Premises and Equipment .. 94 Animal Quarter and Care .. 95 Documentation.

10 95 Production Starting 95 Seed Lot and Cell Bank System .. 96 Operating Principles .. 96 Quality Control .. 97 98 vii ACRONYMS AC Air Conditioner AHU Air Handling Unit API Active Pharmaceutical Ingredient BMR Batch MANUFACTURING Record BPR Batch Packaging Record cGMP Current good MANUFACTURING PRACTICE CFU Colony Forming Units CIP Clean In Place DQ Design Qualification EU End toxin Unit FAT Factory Acceptance Test FMHACA Food.