GOOD MANUFACTURING PRACTICE (GMP) IN THE PHARMACEUTICAL INDUSTRY: A COMPARATIVE STUDY OF COMPANIES IN NEPAL AND THAILAND by Jaya Bir

Karmacharya

A research study submitted in partial fulfillment of the requirements for the degree of Master of Business Administration in the Management of Technology.

Examination Committee

: Prof. Himangshu Paul (Chairman) Dr. Clemens Bechter Dr. Sununta Siengthai : Nepalese : Bachelor of Pharmacy Jadavpur University Calcutta, India : Government of Austria

Nationality Previous Degree

Scholarship Donor

Asian Institute of Technology School of Management Bangkok, Thailand April, 2000

ACKNOWLEDGEMENT The author would like to express his sincere thankfulness and indebtedness to his advisor Prof. Himangshu Paul for his valuable guidance, advice and insights throughout this research study. The author is also thankful to Dr. Clemens Bechter and Dr. Sununta Siengthai members of his examination committee, for their valuable guidance throughout this research. The author would like to express thanks and appreciation to Mr. Anand Kuptamatee, Manufcaturing Manager of Glaxo Wellcome Vidhyasom Limited, Prof. Chomchin Chantaraskul, Deputy Managing Director of Olic (Thailand) Limited, Mr. Apichart Paptipoksut, Managing Director of Community Pharmacy Public Co. Limited, Mr. Kishen Chakravarthy, Marketing Services Manager of Medicap Limited, and Mr. Suchart Chookruvong, General Manager of Polipharm Co., Limited, for giving kind consent to study their company and providing valuable data for his research work. The author would like to express thanks and appreciation to Mr. Kishor Pradhan, Managing Director of Birat Pharma Lab. (P.) Limited, Mr. Mahendra Amatya, Managing Director of Nepal Pharmaceuticals Lab. (P.) Limited, Mr. Jagdish Roongta, Executive Director of National Healthcare (P.) Limited, Mr. Narayan Chetri, Managing Director of Time Pharmaceuticals (P.) limited, Mr. Tirtha Lal Shrestha, Director of Apex Pharmaceuticals (P.) Limited, and Mr. Bishnu Bahadur Shrestha, Acting Deputy General Manager of Royal Drugs Limited, for allowing to study their company and providing valuable data for his research work. Without them helping the author, this research study would not have been possible. The author would like to express a sincere thanks to Dr. Robert Richmond Stroupe of the Center for Language and Educational Technology, Asian Institute of Technology for his active guidance in writing consultations. The author would like to express thanks to Ms. Sunee, the Chief Librarian of Faculty of Pharmacy, Mahidol University for her active support in collection of research articles. The author is indebted to the Government of Austria for providing scholarship to undertake MBA degree in Management of Technology at Asian Institute of Technology of which this research study is a part. The author would like to express thanks to the Dean, School of Management AIT for providing necessary fund for this research work. The author thanks to all members of School of Management, AIT for their support through his study at AIT. Last, but not the least, the author would like to give a special thanks to his wife Prabha, and two daughters, Jenisha, Prajeena and parents. The author would like to express sincere thanks to his father-in-law Dr. Prachanda Pradhan for his encouragement and continuous support through his study at AIT. Without their continuous moral support and encouragement it would have been quite difficult for him to complete his study successfully.

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ABSTRACT Quality, efficacy and safety of drugs have always been a matter of concern for the public. In the manufacture of drugs, overall control is essential to ensure that the customer receives drugs of high quality. Haphazard operation cannot be permitted in the manufacture of drugs. World Health Organization (WHO) has developed guidelines called Good Manufacturing Practice (GMP) to outline steps that should be taken by manufacturers of drugs with the objective of ensuring that their products are of the nature and quality intended. In Nepal, pharmaceutical companies have been developed since 1971. The companies were build and operated without having specific guidelines and regulations. The regulatory act, the Drugs Act 1978, was passed and promulgated only in 1978. As the industrial and regulatory developments have not occurred simultaneously, there exists a wide gap in GMP concepts and its implementation in different companies. To ensure production of quality, safe and efficacious drugs at competitive prices, a detailed understanding of the implementation of GMP norms in the pharmaceutical industry would be essential. As a result this study was done to investigate and evaluated the practical implementation of GMP norms in the pharmaceutical companies in Nepal in comparison with that of Thailand. A conceptual framework was developed based on WHO guidelines on GMP to conduct the study. This study was conducted with six companies in Nepal and five companies in Thailand to evaluate in detail ten components of GMP. This study provides an overview on the situation in practical implementation of GMP in the pharmaceutical companies in Nepal and Thailand. The results of this study have indicated the weakness in practical implementation of GMP in the Nepalese companies as compared to those of Thailand. This study concludes with the recommendations to formulate a national GMP team for developing national GMP guidelines and to enforce the guidelines for effective implementation of GMP for the production of quality, safe and efficacious drugs. The scope for further research is also suggested.

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TABLE OF CONTENTS CHAPTER TITLE Title Page Acknowledgment Abstract Table of Contents List of Abbreviations List of Figures and Graphs List of Tables 1 I INTRODUCTION 1.1 General background 1.2 Rationale of the research study 1.3 Problem Statement 1.4 Objectives 1.4.1 Overall objective 1.4.2 Specific objective 1.5 Conceptual framework of the study 1.6 Scope of Study 1.7 Organization of the report LITERATURE REVIEW 2.1 GMP for Pharmaceutical Products 2.2 Development of GMP 2.3 Importance of GMP 2.4 Comparison of GMP and ISO 9000 2.5 Different Components of GMP 2.5.1 Quality Control 2.5.2 Sanitation and Hygiene 2.5.3 Production 2.5.4 Complaints and Recalls 2.5.5 Self Inspection and Quality Audit 2.5.6 Personnel 2.5.7 Premises 2.5.8 Equipment 2.5.9 Materials 2.5.10 Documentation 2.6 Concluding remarks PAGE i ii iii iv vii viii ix 1 1 1 2 3 3 3 4 4 4 5 5 6 9 12 13 14 15 16 17 17 18 19 20 21 23 25

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III

PHARMACEUTICAL INDUSTRY IN NEPAL AND THAILAND 3.1 World Pharmaceutical Industries 3.2 Policy Issues 3.3 Pharmaceutical Industry in Thailand 3.3.1 Introduction 3.3.2 Categorization of Pharmaceuticals Manufacturers 3.3.3 Pharmaceutical Market of Thailand 3.3.4 Drug Regulation of Thailand 3.3.5 Selected Thai Companies 3.3.5.1 Glaxo Wellcome Vidhyasom Limited 3.3.5.2 Olic (Thailand) Limited 3.3.5.3 Community Pharmacy Public Co., Limited 3.3.5.4 Medicap Limited 3.3.5.5 Polipharm Co., Limited 3.4 Pharmaceutical Industry in Nepal 3.4.1 Introduction 3.4.2 Development of Pharmaceutical Company 3.4.3 Pharmaceutical Market of Nepal 3.4.4 Drug Regulation of Nepal 3.4.5 Selected Nepalese Companies 3.4.5.1 Birat Pharma Laboratory (P.) Limited 3.4.5.2 Nepal Pharmaceuticals Laboratory (P.) Limited 3.4.5.3 National Healthcare (P.) Limited 3.4.5.4 Time Pharmaceuticals (P.) Limited 3.4.5.5 Apex Pharmaceuticals (P.) Limited 3.4.5.6 Royal Drugs Limited METHODOLOGY 4.1 Introduction 4.2 Conceptual Framework 4.3 Selection of companies for study 4.4 Data evaluation criteria 4.5 Development of indicators 4.5.1 Quality Control 4.5.2 Sanitation and Hygiene 4.5.3 Production 4.5.4. Complaints and Recall 4.5.5 Self Inspection and Quality Audit 4.5.6 Personnel

27 27 30 30 30 31 32 32 33 33 34 34 35 35 35 35 36 37 37 38 38 39 39 40 40 40 42 42 42 44 45 46 46 47 48 49 50 51

IV

4.5.7 Premises
2 4.5.8 Equipment 4.5.9 Materials 4.5.10 Documentation 4.6 Overall calculation criteria

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52 53 53 55

RESULTS AND DISCUSSIONS 5.1 Introduction 5.2 Factor weight for each component of GMP 5.3 Results and discussion of each component of GMP 5.3.1 Quality Control 5.3.2 Sanitation and Hygiene 5.3.3 Production 5.3.4. Complaints and Recalls 5.3.5 Self Inspection and Quality Audit 5.3.6 Personnel

57 57 57 58 58 59 60 62 63 64

5.3.7 Premises
3 5.3.8 Equipment 5.3.9 Materials 5.3.10 Documentation 5.3.11 Average score of GMP 5.3.12 Weighted scores for each company 5.4 Concluding remarks VI CONCLUSIONS AND RECOMMENDATIONS 6.1 Introduction 6.2 Summary 6.3 Conclusions 6.4 Usefulness of the methodology 6.5 Limitations of the study 6.6 Recommendations 6.7 Direction for future research 6.8 Concluding remarks REFERENCE APPENDIX

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66 67 68 69 70 72 74 74 74 75 77 77 78 78 79 80 84

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LIST OF ABBREVIATIONS FULL FORM ABBREVIATION World Health Organization WHO Good Manufacturing Practice GMP Department of Drug Administration, Nepal DDA Food and Drug Administration FDA The Broker Group Limited BGL Association of South East Asian Nations ASEAN International Organization of Standardization ISO Center for Drug Evaluation and Research CDER International Federation of Pharmaceutical Manufacturers Associations IFPMA Quality Control QC Sanitation and Hygiene SH Production PROD Complaints and Recalls CR Self Inspection and Quality Audit SIQA Personnel PER Premises PREM Equipment EQIP Materials MAT Documentation DOC Standard Operating Procedure SOP Government Pharmaceutical Organization, Thailand GPO Glaxo Wellcome Vidhyasom Limited GWL Olic (Thailand) Limited OTL Community Pharmacy Public Co., Limited. CPL Medical Limited . MCL Poliphram Co. Limited. PCL Royal Drugs Research Laboratory RDRL Birat Phrama Laboratory (P.) Limited BPL Nepal Pharmaceuticals Laboratory (P.) Limited. NPL National Healthcare (P.) Limited. NHP Time Pharmaceuticals (P.) Limited. TPL Apex Pharmaceuticals (P.) Limited APL Royal Drugs Limited RDL United Nations Industrial Development Organization UNIDO United Nations Development Program UNDP United Nations International Children Education Fund UNICEF

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LIST OF FIGURES AND GRAPHS FIGURE 2.1 2.2 2.3 2.4 2.5 3.1 3.2 4.1 4.2 4.3 TITLE Sources of Risk from Drug Products Components of Good Manufacturing Practice Process Validation Life Cycle Activity of Process Validation Labels used in manufacturing tablets. World Pharmaceutical Market, 1997 Pharmaceutical Industry Structure of Thailand Logical steps of research Components of good manufacturing practice Conceptual framework of the study PAGE 10 13 17 17 23 28 31 42 43 43

GRAPH 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 5.10 5.11 5.12 6.1

TITLE Quality Control Sanitation and Hygiene Production Complaints and Recall Self Inspection and Quality Audit Personnel Premises Equipment Materials Documentation Average score of GMP Summary of the weighted score GMP scores of Nepalese and Thai Companies

PAGE 59 60 61 62 63 64 65 66 67 68 69 71 75

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LIST OF TABLES TABLE 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 4.10 4.11 4.12 4.13 5.1 5.2 5.3 TITLE Identification of pipelines Major manufacturing/laboratory documentation and records Worlds Top 10 Pharmaceutical Companies, 1998 A typology of the worlds pharmaceutical industries Thai pharmaceutical market share of different companies in 1998 The pharmaceutical market share distribution of Nepal in 1997 List of companies selected for study in Thailand List of companies selected for study in Nepal Calculation for Quality Control Calculation for Sanitation and Hygiene Calculation for Production Calculation for Complaints and Recall Calculation for Self-Inspection and Quality Audit Calculation for Personnel Calculation for Premises Calculation for Equipment Calculation for Materials Calculation for Documentation Format with symbols used for calculation of results Factor weight calculation for each of 10 components of GMP Summary of the scores for GMP components in percentage Summary of the weighted scores for GMP components PAGE 21 24 29 29 32 37 44 44 47 48 49 50 50 51 52 53 53 55 56 58 73 73

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