MEDICINES CONTROL COUNCIL - mccza.com

1 SA Guide to GMP. MEDICINES CONTROL COUNCIL . GUIDE TO GOOD MANUFACTURING PRACTICE. FOR MEDICINES IN SOUTH AFRICA. This document has been prepared to serve as a guidance document on the requirements for Good Manufacturing Practice applicable to the manufacturing of MEDICINES . It is not intended as an exclusive approach. COUNCIL reserves the right to request for any additional information to establish the safety, quality and efficacy of a medicine and may make amendments in keeping with the knowledge which is current at the time of consideration of data accompanying applications for registration of MEDICINES . Alternative approaches may be used but these must be scientifically and technically justified. The MCC is committed to ensure that all MEDICINES gaining market approval will be of the required quality, safety and efficacy.

2 This Guide is based entirely on the Guide to Good Manufacturing Practice for Medicinal Products , version PE 009-2 dated 1 July 2004 published by the Pharmaceutical Inspection Cooperation Scheme (PIC/S). The modifications to that Guide and its adoption as the South African Guide to Good Manufacturing Practice is done so with the expressed permission of the PIC/S. Version 1 - Implementation 1997. Version 1 - Chapter 9 (Validation) reformatted January 2004. Version 2 - Sept 2005 adopted PIC/ s gmp Guide of July 2004 - Implementation January 2006. Version 3 - Sept 2008 update to amend Introduction and include requirements for Quality September 2008. Product Review ( ) , Risk Management ( ), On-going stability programme ( ), Analytical Method Validation (Annex 15 ) and Glossary, keeping of Reference and Retention samples (Annex 19), Quality Risk Management (Annex 20).

3 Version 4 - March 2009 update to amend Radiopharmaceuticals (Annex 3), Herbal March 2009. Medicinal Products (Annex 7). Due date for comment Version 3 31 January 2009. Due date for comment Version 4 30 June 2009. Version 5 (consolidates comments on versions 3 and 4) - Implementation 1 November 2010. REGISTRAR OF MEDICINES . MS M HELA. SA Guide to GMP Jun10 v5 August 2010 Page 1 of 158. SA Guide to GMP. TABLE OF CONTENTS. Page INTRODUCTION 11. 1 CHAPTER 1 - QUALITY MANAGEMENT 13. Principle 13. Quality Assurance 13. Good Manufacturing Practice for Medicinal products (GMP) 14. Quality CONTROL 14. Product Quality Review 15. Quality Risk Management 16. 2 CHAPTER 2 - PERSONNEL 17. Principle 17. General 17. Key Personnel 17. Training 18. Personal Hygiene 19.

4 3 CHAPTER 3 - PREMISES AND EQUIPMENT 20. Principle 20. Premises 20. General 20. Production Area 20. Storage Areas 21. Quality CONTROL Areas 22. Ancillary Areas 22. Equipment 22. 4 CHAPTER 4 - DOCUMENTATION 23. Principle 23. General 23. Documents required 24. Specifications 24. Specifications for starting and packaging materials 24. Specifications for intermediate and bulk products 24. Specifications for finished products 24. Manufacturing Formulations and Processing Instructions 24. Packaging Instructions 25. Batch Processing Records 25. Batch Packaging Records 26. SA Guide to GMP Jun10 v5 August 2010 Page 2 of 158. SA Guide to GMP. Table of contents continued Procedures and records 27. Receipt 27. Sampling 27. Testing 27. Other 27. 5 CHAPTER 5 PRODUCTION 29.

5 Principle 29. General 29. Prevention of cross-contamination in production 30. Validation 30. Starting materials 30. Processing operations - Intermediate and bulk products 31. Packaging materials 31. Packaging operations 32. Finished products 33. Rejected, recovered and returned materials 33. 6 CHAPTER 6 - QUALITY CONTROL 34. Principle 34. General 34. Good Quality CONTROL Laboratory Practice 34. Documentation 35. Sampling 35. Testing 36. On-going stability programme 36. 7 CHAPTER 7 - CONTRACT MANUFACTURE AND ANALYSIS 38. Principle 38. General 38. The Contract Giver 38. The Contract Acceptor 38. The Contract 49. 8 CHAPTER 8 - COMPLAINTS AND PRODUCT RECALL 40. Principle 40. Complaints 40. Recalls 40. 9 CHAPTER 9 SELF-INSPECTION 42. Principle 42.

6 SA Guide to GMP Jun10 v5 August 2010 Page 3 of 158. SA Guide to GMP. Table of contents continued ANNEXES. Annex 1 Manufacture of sterile medicinal products 43. Principle 43. General 43. Isolator technology 46. Blow/fill/seal technology 46. Terminally sterilised products 46. Aseptic preparation 47. Personnel 47. Premises 48. Equipment 49. Sanitation 50. Processing 50. Sterilisation 51. Sterilisation by heat 52. Moist heat 52. Dry heat 53. Sterilisation by radiation 53. Sterilisation with ethylene oxide 53. Filtration of medicinal products which cannot be sterilised in their final container 54. Finishing of sterile products 54. Quality CONTROL 55. Annex 2 Manufacture of biological medicinal products for human use 56. Scope 56. Principle 56.

7 Personnel 56. Premises and Equipment 57. Animal quarters and care 58. Documentation 58. Production 58. Starting materials 58. Seed lot and cell bank system 59. Operating principles 59. Quality CONTROL 60. Annex 3 Manufacture of radiopharmaceuticals 61. Principle 61. Introduction 61. Quality Assurance 62. SA Guide to GMP Jun10 v5 August 2010 Page 4 of 158. SA Guide to GMP. Table of contents continued ANNEXES. Annex 3 Manufacture of radiopharmaceuticals - cont Personnel 63. Premises and equipment 63. Documentation 64. Production 64. Quality CONTROL 65. Reference and Retention samples 65. Distribution 66. Glossary 66. Annex 4 Manufacture of veterinary medicinal products other than 67. immunologicals Manufacture of premixed for medicated feeding stuffs 67.

8 The manufacture of ectoparasiticides 67. The manufacture of veterinary medicinal products containing penicillins 67. Retention of samples 68. Sterile veterinary medicinal products 68. Annex 5 Manufacture of immunological veterinary medical products 69. Principle 69. Personnel 69. Premises 70. Equipment 72. Animals and animal houses 73. Disinfection waste disposal 73. Production 73. Starting materials 73. Quality CONTROL 76. Annex 6 Manufacture of medicinal gases 77. Principle 77. Personnel 77. Premises and equipment 77. Premises 77. Equipment 77. Documentation 78. Production 78. Bulk production 78. Filling and labelling 79. Quality CONTROL 80. Storage and release 81. SA Guide to GMP Jun10 v5 August 2010 Page 5 of 158. SA Guide to GMP. Table of contents continued ANNEXES.

9 Glossary 82. Annex 7 Manufacture of herbal medicinal products 84. Principle 84. Premises 85. Storage areas 85. Production area 85. Equipment 85. Documentation 85. Specifications for starting materials 85. Processing instructions 86. Quality CONTROL 86. Sampling 86. Annex 8 Sampling of starting and packaging materials 88. Principle 88. Personnel 88. Starting materials 88. Packaging Material 89. Annex 9 Manufacture of liquids, creams and ointments 90. Principle 90. Premises and Equipment 90. Production 90. Annex 10 Manufacture of pressurised metered dose aerosol preparations for 91. inhalation Principle 91. General 91. Premises and Equipment 91. Production and Quality CONTROL 91. Annex 11 Computerised systems 93. Principle 93. Personnel 93.

10 Validation 93. System 93. Annex 12 Use of ionising radiation in the manufacture of medicinal products 95. Introduction 95. Responsibilities 95. Dosimetry 95. Validation of the process 96. Commissioning of the plant 96. SA Guide to GMP Jun10 v5 August 2010 Page 6 of 158. SA Guide to GMP. Table of contents continued ANNEXES. Annex 12 Use of ionising radiation in the manufacture of medicinal products cont. General 96. Gamma irradiators A Design 96. B Dose mapping 97. Electron Beam Irradiators: A Design 97. B Dose mapping 98. Re-commissioning 98. Premises 98. Processing 98. Gamma irradiators 99. Electron Beam Irradiators 99. Documentation 99. Microbiological monitoring 99. Annex 13 Manufacture of investigational medicinal products 100. Principle 100.