Pharmacovigilance in Asian Countries

C O M PA R AT I V E Pharmacovigilance Systems
A N A LY S I S
in Five Asian Countries
n e pa l
bangladesh
philippines
thailand
cambodia
Comparative Analysis of
Pharmacovigilance Systems
in Five Asian Countries
Jude Nwokike
Elisabeth Ludeman
Melissa Thumm
S E P T E M B E R 2013
This report is made possible through an interagency agreement between the US Food and Drug Administration (FDA)
and the US Agency for International Development (USAID). The combined support enabled the Systems for Improved
Access to Pharmaceuticals and Services Program to implement the study, under the terms of cooperative agreement
number AID-OAA-A-11-00021. The opinion expressed in this report does not necessarily reflect the official position
of the FDA, the USAID, or the US Government. The contents are the responsibility of Management Sciences for Health
and do not necessarily reflect the views of USAID or the United States Government.
About SIAPS
The goal of the Systems for Improved Access to Pharmaceuticals and Services (SIAPS) Program is to assure the availability
of quality pharmaceutical products and effective pharmaceutical services to achieve desired health outcomes. Toward
this end, the SIAPS result areas include improving governance, building capacity for pharmaceutical management and
services, addressing information needed for decision-making in the pharmaceutical sector, strengthening financing
strategies and mechanisms to improve access to medicines, and increasing quality pharmaceutical services.
Recommended Citation
This report may be reproduced if credit is given to SIAPS. Please use the following citation.
Systems for Improved Access to Pharmaceuticals and Services (SIAPS) Program. 2013. Comparative Analysis of
Pharmacovigilance Systems in Five Asian Countries. Submitted to the US Agency for International Development
by the Systems for Improved Access to Pharmaceuticals and Services (SIAPS) Program. Arlington, VA: Management
Sciences for Health.
Key Words
Pharmacovigilance, medicine safety, post-marketing surveillance, quality control, quality assurance, medicine
information, medication error, treatment failure, regulatory system
Systems for Improved Access to Pharmaceuticals and Services

Center for Pharmaceutical Management
Management Sciences for Health
4301 North Fairfax Drive, Suite 400
Arlington, VA 22203 USA
Telephone: 703.524.6575
Fax: 703.524.7898
E-mail: [email protected]
Website: www.siapsprogram.org
2 co m pa r at i v e a n a lys i s o f p h a r maco v i g i l a n c e s ys t e m s i n f i v e a s i a n co u n t r i e s
Contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Acronyms and Abbreviations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Executive Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Study Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Current State of Pharmaceutical Market in Asia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Selected Recommendations and Options for Enhancing PV Systems. . . . . . . . . . . . . . . . . . 16
Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Background on Asian Pharmaceutical Market. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Definition and Scope of Pharmacovigilance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Study Objectives and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Objectives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Study Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Review of Regulatory and Pharmacovigilance Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Medication Mishaps Have Catalyzed Medicines Regulation . . . . . . . . . . . . . . . . . . . . . . . . . 27
Poor Quality Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Challenges for Pharmacovigilance Systems in Asia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Comparative Analysis of Results of Assessment of Pharmacovigilance Systems. . . . . . 37
Pharmacovigilance at the National Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Governance, Policy, Law, and Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Governance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Policy, Law, and Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Provisions That Mandate Market Authorization Holders to Conduct
Post-Marketing Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Systems, Structure, and Stakeholder Coordination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
PV Center or Unit with a Clear Mandate, Structure, Roles, and Responsibilities. . . . . . . . 45
Budget for PV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Quality Control Lab (or Unit) with Clear Mandate, Structure, and Functions. . . . . . . . . . 46
National PV Guideline/National Standard Operating Procedures for PV and QC. . . . . . . 46
Medicines Safety Advisory Committee and Quality Control Advisory Committee. . . . . . 47
PV Medicines Information Service. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Core Communication Technologies for PV/Core PV Reference Material in
PV Unit/Drug Information Center. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Core PV Topics in Pre-Service Training Curricula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
PV Stakeholder Coordination Mechanism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
WHO International Drug Monitoring Programme Membership. . . . . . . . . . . . . . . . . . . . . 47
Quality Management System for PV and Quality Assurance. . . . . . . . . . . . . . . . . . . . . . . . . 48
Signal Generation and Data Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Systems for Coordination and Collation of PV Data from all Sources within a Country . . 51
Existence of a Form for Reporting Suspected ADRs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Risk Assessment and Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Number of Spontaneous Reports. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
co n t e n t s 3
Risk Management and Communication. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Medicine Safety Information Requests Received and Addressed in the Last Year. . . . . . . . 57
Product Quality Surveillance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
PV Capacity at the National Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Options for Strengthening Pharmacovigilance at
the National Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Strengthening Regulatory Policies and Framework. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Ensuring Convergent Regional and International Regulations . . . . . . . . . . . . . . . . . . . . . . . 67
Improving Information Sharing and Participation in Regional Harmonization
Initiatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Reforming Organizational Structure to Achieve Integrated Safety Surveillance. . . . . . . . . 69
Ensuring Efficient Safety Surveillance and Reduction ofRegulatory Burden. . . . . . . . . . . . 69
Improving Funding for PV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Developing Comprehensive PV Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Strengthening Spontaneous Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Confronting Falsified and Substandard Products. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
PV Results in Public Health Programs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Systems, Structure, and Stakeholder Coordination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Signal Generation and Data Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Risk Assessment and Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Risk Management and Communication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
PV Capacity at the PHP Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Options for Strengthening PV Systems at the PHP Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
PV Results at the Service Delivery Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Policy, Law, and Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Systems, Structure, Stakeholder Coordination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
PV Capacity at the Health Facility Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Options for Improving PV at the Service Delivery Level (Health Facilities and
Community Pharmacies). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
PV Results in the Pharmaceutical Industry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Signal Generation and Data Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Risk Assessment and Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Options for Improving PV in Pharmaceutical Industries. . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
PV Results at the Civil Society Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
PV Capacity in Civil Societies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Options for Improving PV in Civil Societies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Comparison of Performance and Capacity of PV in Selected Asia Countries. . . . . . . . . . 101
Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Global and Regional Initiatives for Strengthening Pharmacovigilance
Systems in Asia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Financing Institutions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Technical Institutions and Programs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Regional Institutions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Annexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Annex A. Medication Mishaps and Related Regulatory Forms. . . . . . . . . . . . . . . . . . . . . . . 108
Annex B. Pharmacovigilance Profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
Annex C. Country Profiles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
Annex D. Assessment Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Annex E. PV Topics in Curriculum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Annex F. Thailand Health Product Adverse Event Report Form. . . . . . . . . . . . . . . . . . . . . . 127
Annex G. Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
List of Tables
Table 1. Summary of Pharmaceutical Market in Studied Countries . . . . . . . . . . . . . . . . . . . 20
Table 2. Functions of Select PV Initiatives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Table 3. WHO-UMC Membership Status. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Table 4. Comparison of Drug Safety Systems Across SRAs . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Table 5. Countries of Manufacture of Cambodia Registered Products . . . . . . . . . . . . . . . . 32
Table 6. Regional Harmonization Initiatives Member Countries . . . . . . . . . . . . . . . . . . . . . . 33
Table 7. PV Governance at the National Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Table 8. Content Analysis of PV Regulatory Requirements for the Pharmaceutical
Industry in Two Countries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Table 9. Content Analysis of Pharmaceutical Legislation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Table 10. Summary of Policy, Law, and Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Table 11. Funding for PV Activities in Five Countries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Table 12. Grants to Support PV. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Table 13. Availability of Quality Control Lab Services in Five Asian Countries. . . . . . . . . . 46
Table 14. System, Structure, and Stakeholder Coordination at the National Level . . . . . . . 49
Table 15. PV Data Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Table 16. Data Mining Methods Used in the Study Countries. . . . . . . . . . . . . . . . . . . . . . . . 52
Table 17. Signal Generation and Data Management at the National Level. . . . . . . . . . . . . . 52
Table 18. Actual ADR Reporting versus Expected . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Table 19. Risk Assessment and Evaluation at the National Level. . . . . . . . . . . . . . . . . . . . . . 56
Table 20. Number of Medical Products Sampled and Analyzed for Quality . . . . . . . . . . . . 58
Table 21. Public Communication Activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Table 22. Other Medicine Safety Regulatory Actions Taken Besides ADR Reporting
in 2011. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Table 23. Risk Management and Communication. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Table 24. Summary of Indicators related to Product Quality Assurance. . . . . . . . . . . . . . . . 63
Table 25. Results of System, Structure, and Stakeholder Coordination in
Public Health Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Table 26. Results of Signal Generation and Data Management in Public Health
Programs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
co n t e n t s 5
Table 27. Results of Risk Management and Communication in Public Health
Programs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Table 28. Number of Health Facilities Surveyed. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Table 29. Results of Systems, Structure, and Stakeholder Coordination at
Service Delivery Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Table 30. Results of PV Related Activities Among Private Pharmacies Surveyed. . . . . . . . 82
Table 31. Results of Signal Generation and Data Management at
Health Facilities Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Table 32. Summary of Results among Private Pharmacies Surveyed. . . . . . . . . . . . . . . . . . . 84
Table 33. Results of Risk Assessment and Evaluation at Service Delivery Level . . . . . . . . . 84
Table 34. Results of Risk Management and Communication at Service
Delivery Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Table 35. Results in Private Pharmacies Surveyed at Service Delivery Level. . . . . . . . . . . . 86
Table 36. Results of Policy, Law and Regulation in the Pharmaceutical Industry. . . . . . . . 90
Table 37. Results of Systems, Structures, and Stakeholder Coordination in
Pharmaceutical Industries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Table 38. Availability of Forms in Pharmaceutical Industry. . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Table 39. Results of Risk Assessment and Evaluation in Pharmaceutical Industry. . . . . . . 92
Table 40. Industry PV Capacity and Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Table 41. Results of Policy, Law, and Regulation at Civil Society Level. . . . . . . . . . . . . . . . . 97
Table 42. Results of System, Structure, and Stakeholder Coordination at
Civil Society Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Table 43a. Classification Scheme for PV Capacity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Table 43b. Performance Card . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
List of Figures
Figure 1. Map of Asian Countries Included in Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Figure 2. Pharmaceutical Market Size of Asian Countries in Assessment . . . . . . . . . . . . . . . 21
Figure 3. National PV Systems Capacity in Five Asian Countries. . . . . . . . . . . . . . . . . . . . . 65
Figure 4. National Public Health Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Figure 5. PV Capacity at the Health Facility Level. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Figure 7. PV Capacity in Pharmaceutical Companies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Figure 8. PV Capacity in Device Companies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Figure 9. PV Capacity in Clinical Research Organizations. . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Figure 10. PV Capacity in Consumer Groups. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Figure 11. PV Capacity in Professional Associations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Foreword
Bangladesh
Pharmacovigilance is not a new concept in Bangladesh. As known, it is not about the
medicines but the value it places for health, welfare and safety of any patients in the
healthcare systems; yet the importance and attention given to it by the authorities has not
been significant over the years. We are thankful to MSH/SIAPS program for this assessment
report which has provided us with important and valuable recommendations to identify
areas and take initiatives. Taking from the recommendations; important measures have been
taken to strengthen the Adverse Drug Reaction Monitoring (ADRM) cell and the Adverse
Drug Reaction Advisory Committee (ADRAC), as a result of which now Bangladesh has
launched the National Pharmacovigilance Program and the national regulatory authority, the
Directorate General of Drug Administration (DGDA) has been recognized as the National
Pharmacovigilance Center by the Ministry of Health and Family Welfare (MOHFW). This is
just the beginning, we strive to learn from our experience and undertake corrective actions to
improve. All these efforts could not be accomplished without the active technical assistance
of MSH/SIAPS program and financial assistance from USAID.
Cambodia
The practice of pharmacovigilance as a systematic method to ensure patient safety is
relatively new for Cambodia in which most health professionals trained in Cambodia are
not yet familiar with the subject and concept of PV. A national pharmacoviglance system
was established in 2008, following establishment of the Cambodian PV Center in 2008,
revision of the National Medicine Policy to include medicine safety statements in 2010, and
introduction of the national PV guidelines in 2012 to improve medicine safety monitoring in
Cambodia within both the public and private sectors, including formation of the Cambodian
PV Center. This significant milestone represented an important first step to establishing a
comprehensive PV system within the Cambodia health system to systematically monitor,
record, and share adverse drug events (ADEs) and adverse drug reactions (ADRs) occurring
in the country.
The assessment on pharmacovigilance system and its performance in Cambodia indicates

that Cambodia has made important progress in introducing a system to achieve medicine
safety monitoring and promote public health, but much works remain to be done. This
assessment has provided important and valuable recommendations to address identified gaps
and further enhance the existing PV system in Cambodia. As a result of the recommendation,
foreword 7
important step has been taken by the PV center to strengthen ADR reporting in both public
and private health facilities and planning to revise regulation and guideline on medicinal
product safety for pharmaceutical companies based on the recommendations provided. The
experiences and lessons draw from other Asian countries participated in the assessment will
further provide foundation and concepts of pharmacovigilance system that are useful for
Cambodia to improve and strengthen our own system. This would not be possible without
the support of USAID and FDA who sponsored the project.
Philippines
We are thankful for this PV report entitled Comparative Analysis of Pharmacovigilance
Systems in Five Asian Countries. As PV is an evolving discipline, in the Philippines, we strive
to learn from our experience and undertake corrective measures to improve. After all, PV
is not about the medicines but the value it places for the health, welfare and safety of any
patients under the care of health systems. Yet, ironically, the attention and importance given
to PV by most authorities is low.
The key driver to improvement is in finding the champions willing to innovate and take
initiative to evolve PV to the next level, and, finding the right mix of political support and
administrative capacities to create a PV culture with technical proficiency.
Nepal
In context of Nepal, we are already a member of WHO-UMC Collaborating Center for
International Drug Monitoring and reporting ADR reports since 2006. Seven hospitals
are participating in the system. Pharmacovigilance though a subject matter of global
importance and the entire humanity, it is relatively new area even among its stakeholders
so in the country. Assessment on Pharmacoviglance system and its performance has been
undertaken by this department with the approval of Ministry of Health and Population. The
assessment has clearly indicated the status of PV in the Asian region and the possibilities of
learning from each other. Following this assessment study of PV in the country, we feel that
the healthcare, medical, pharmaceuticals and other stakeholders are well sensitized. This
study has created a conclusive environment for its system development in the Asian region
including Nepal. I think this is the right time to strike to strengthen the PV system in the
country with the solidarity of all stakeholders and the supporting agencies.
I would like to express my sincere thanks to SIAPS/MSH for supporting this study in Nepal.
I take this opportunity to thank all the stakeholders involved in this study, Ms. Elisabeth
Ludeman and Mr. Navin Prasad Shrestha for coordinating the study.
Thailand
Pharmacovigilance system in Thailand was given establishment in 1983. The national center
was established under the Food and Drug Administration with ADR monitoring program
as its main focus. Starting from 176 total reports by several tertiary hospitals during the first
year, the number of reports is now more than 50,000 annually with pharmacists as a major
reporter. Today the scope of work has been expanded to cover all health products and to
involve various stakeholders in health system including consumers, market authorization
holders, as well as, health facilities, i.e., drugs stores, physician clinics, private hospitals,
and all levels of public hospitals, ranging from community hospitals to tertiary hospitals to
academic and research hospitals.
Although the role of the national center has been well accepted, the extent of
pharmacoviglance system and functions must now be extended beyond its initial
responsibilities. Collaboration among stakeholders as well as supporting their demands on
patient safety becomes vital challenges influencing system effectiveness. Influx of health
information due to the advancing of information technology and health products from
the free trade area is another challenge to the system. Enhancing system performance
requires coordination and integration of all concerned parties not only nationally but also
internationally.
Knowing where we are now is the initial reference to move our system forwards. Learning
from certain Asian countries with comparable resources is the next advantage for us to
cooperate as well as collaborate to strengthen each own pharmacovigilance system. Thanks
to USAID for the initiative to assess the pharmacovigilance system in Thailand together with
other Asian countries. The information and learning experience gained from the project not
only benefits the countries being studied but could also provide foundation and concepts of
pharmacoviglance system for others.
foreword 9
Acronyms and Abbreviations
ADR adverse drug reaction

AE adverse event
AERS adverse event reporting system
AHWP Asian Harmonization Working Party
AIDS acquired immunodeficiency syndrome
APEC Asia Pacific Economic Collaboration
ASEAN Association of Southeast Asian Nations
BCPNN Bayesian confidence propagation neural network
CRO Clinical Research Organization
DDF Department of Drugs and Food [Cambodia]
DIC Drug Information Center
DSUR development safety updated report
DTC Drug And Therapeutics Committee
EMA European Medicines Agency
EU European Union
FDA US Food And Drug Administration
FDAAA Food And Drug Administration Amendments Act
FP family planning
Global Fund Global Fund To Fight AIDS, Tuberculosis And Malaria
GMP Good Manufacturing Practice
HIV human immunodeficiency virus
HPVC Health Product Vigilance Center (Thailand)
ICH International Conference on Harmonization of Technical
Requirements for Registration of Pharmaceuticals for Human Use
ICSR individual case safety report
IOM Institute of Medicine [United States]
IPAT Indicator-Based Pharmacovigilance Assessment Tool
ISO International Standards Organization
MAH Marketing Authorization Holder
MedDRA Medical Dictionary for Regulatory Activities
MSH Management Sciences For Health
NDP National Drug Policy
NML National Medicines Laboratory
NMP National Medicines Policy
NRA National Regulatory Authority
PHP Public Health Program
PMA post-marketing alert
PPWG Pharmaceutical Product Working Group
PQM Promoting the Quality of Medicines [USP]
PRAC Pharmacovigilance Risk Assessment Committee [EMA]
PSUR Periodic Safety Update Report
PV pharmacovigilance
QA quality assurance
QC quality control
RH reproductive health
RHI regional harmonization initiatives
RMP Risk Management Plan
SOP Standard Operating Procedure
SIAPS Systems for Improvised Access to Pharmaceuticals and Services
Program [USAID]
SMP Safety Monitoring Program [Thailand]
SOP standard operating procedure
SPS Strengthening Pharmaceutical Systems Program [USAID]
SRA Stringent Regulatory Agency
STG standard treatment guideline
TB tuberculosis
UNICEF United Nations Children’s Fund
USAID US Agency For International Development
USD US dollars
USP United States Pharmacopeia
VAERS Vaccine Adverse Event Reporting System
WHO World Health Organization
ac r o n ym s a n d a b b r e v i at i o n s 11
Acknowledgments
Authors
Jude Nwokike, Elisabeth Ludeman, Melissa Thumm
Contributors
Bangladesh: Md. Mostafizur Rahman
Cambodia: Chean R. Men
Nepal: Navin Prasad Shrestha
Philippines: Josephine Carmela B. Marcelo
Thailand: Rungpetch C. Sakulbumrungsil
Reviewers
India
Vivek Ahuja
Program for Applied Technologies in Health
Korea
BJ Park
Korea Institute of Drug Safety and Risk Management
Philippines
Kenneth Hartigan-Go
Philippines Food and Drug Administration
United States of America

Patrick Lukulay
United States Pharmacopeia/Promoting the Quality of Medicines program
Andy Stergachis
University of Washington, Seattle, WA
Louis An, Mohan P. Joshi, Lassane Kabore (intern), David Lee, Patricia Paredes,
and Helena Walkowiak
Management Sciences for Health/Systems for Improved Access to Pharmaceuticals
and Services (SIAPS) Program
Review, Project Coordination, Guidance

US Agency for International Development
Anthony Boni, Maria Miralles
US Food and Drug Administration (FDA)

Joan Blair, Katherine Bond, Beverly Corey, Gerald Dal Pan, Justina Molzon,
Charles Preston, Mary Lou Valdez
Executive Summary
Access to medicine is improving in low- and middle-income countries (LMICs), thanks to

the efforts of global health initiatives and also to the commitment of national governments. All countries
Medicines and other health commodities are required to be safe, effective, and of good assessed
quality to achieve their intended purpose. However recent history records several incidences have national
of harm from poor quality or unsafe products. The increasing influx of these products into
medicine laws
global supply chains can diminish the significant improvements in access and compromise
in place that
the success of public health programs. The primary objective of pharmaceutical regulation
is to safeguard the public from unsafe medical products. Countries can achieve that by include legal
establishing a comprehensive pharmacovigilance (PV) system. In many low and middle- provisions
income countries (LMICs), PV activities are fragmented, weak, and unable to protect the for medicine
public adequately. Recognizing the importance of assisting countries protect the public from safety, but their
unsafe and poor quality medicines, the US Agency for International Development (USAID) PV regulatory
and the Food and Drug Administration (FDA) funded the Systems for Improved Access to
requirements
Pharmaceuticals and Services (SIAPS) Program through an interagency agreement to assess
vary greatly.
PV systems’ performance in selected Asian countries. The objectives of the assessment are
to benchmark national systems’ performance, identify replicable and successful experiences,
map the contributions of donor agencies, and recommend options for enhancing PV and
post-market surveillance systems’ capacity and performance.
Study Methods
We conducted a review of the regulatory and PV systems literature with a focus on the Asia
region. A comprehensive assessment of the PV system in Bangladesh, Cambodia, Nepal,
Philippines, and Thailand was conducted by teams of local consultants and data collectors and
detailed report developed for each country. Using primary data from the individual country
assessments, we conducted comparative analysis of the five components of the PV system
including Governance and Policy, Law, and Regulation; Systems, Structure, and Stakeholder
Coordination; Signal Generation and Data Management; Risk Assessment and Evaluation;
and Risk Management and Communication
Current State of Pharmaceutical Market in Asia

The Asian pharmaceutical market size is estimated at 140 billion US dollars (USD),
with China and Japan accounting for about 70% of the total value. Most of the market
is dominated by generic medicines. Of the countries studied, Thailand has the largest
pharmaceutical market size with over USD 4.4 billion and Nepal has the smallest with
USD 1.4 million.
e x e c u t i v e s u m ma ry 13
Results
Pharmacovigilance at the National Level
Governance, Policy, Law, and Regulation
Of the five Asian countries studied, Bangladesh, Philippines, Thailand have regulatory
frameworks, regulatory registers and governance structures. All countries have registers for
approved medical products, licensed pharmaceutical premises, and licensed pharmaceutical
personnel in place. All countries assessed have national medicine laws in place that include
Although all legal provisions related to medicine safety but their PV regulatory requirements vary greatly.
countries have Cambodia and the Philippines have legal provisions mandating industry to report adverse
a national events but only the Philippines mandates industry to conduct post-marketing surveillance
of specified products based on stringent regulatory authority requirements. Generally risk
PV center and
assessment and evaluation and also risk management practices are not explicitly required in
an adverse
the countries legislations.
events form,
less than half Systems, Structures, and Stakeholder Coordination
of the health All countries have a national PV center. Thailand has a dedicated annual budget for PV-
facilities related activities. Cambodia and Thailand have national PV guidelines in place. Cambodia,
surveyed Nepal, and Thailand have Medicines Safety Advisory Committees that meet regularly (at least
have the form once within the past year) and have documented decision-making processes, however only
Thailand’s Advisory Committee has policies that address conflict of interest. Although all the
available
five countries address elements of product quality assurance within their National Regulatory
to them. Authorities (NRAs), only the Philippines has a formal quality management system in place
and only Thailand has a WHO pre-qualified quality control laboratory. Cambodia, Nepal,
Philippines, and Thailand are official members of the WHO International Drug Monitoring
Programme. During this assessment Bangladesh initiated plans to join the WHO program.
Signal Generation and Data Management

All countries have a standardized national adverse events (AE) form. Thailand AE forms
is for all health products and collect data on suspected ADRs, product quality issues,
medication error, and treatment failure. Thailand and Philippines implement consumer
reporting. Availability of the AE reporting forms within service delivery points was found to
be limited. Only 41% of health facilities and 21% of pharmacies sampled across five countries
reported existence of AE forms within their facility. Significant underreporting was observed
in all countries, with the exception of Thailand.
Risk Assessment and Evaluation

Risk assessment and evaluation was identified by the assessment as the weakest component of
the PV system across all the countries. Only the NRA in Thailand reported conducting active
surveillance activity in the last five years.
Risk Management and Communication

Thailand and the Philippines have medicine information processes that are functioning
with a minimum of one information request received and responded to per month. Nepal
and Thailand regularly publish medicines safety bulletins. All countries reported use of
prequalification schemes for procurement decisions related to at least some medical products.
Nepal, the Philippines, and Thailand estimated the levels of unregistered medicines in
their respective markets to be less than one percent, while Cambodia estimates the levels
of unregistered medicines at 30%. Bangladesh also estimates high levels of unregistered
medicines within its market. All countries studied reported that medical products were both
sampled and analyzed for quality in national medicines laboratories in 2011. Encouragingly,
Cambodia, Philippines, and Thailand reported alerting healthcare workers and the public
within three weeks of the detection of a medicine safety concern. The ASEAN post-marketing
alert (PMA) mechanism for sharing information relating to defective or unsafe medicinal
products seems to provide an underutilized opportunity for collaboration to safeguard the
supply chain in the member countries.
Pharmacovigilance in Public Health Programs For all countries,

The assessment included interviews with representatives from 19 national HIV and AIDS, adverse events
malaria, and TB immunization programs. Among PHPs assessed, 84% reported having a reporting in the
policy document that mentions PV and product quality assurance. Thirty seven percent PHPs was low and
were found to have a PV point of contact assigned responsibility for monitoring medicine uncoordinated
safety within the program. Forty two percent reported keeping a log or database of PV
with the national
data collected. For all countries adverse events reporting in the public health programs
PV system.
(PHPs) were low and uncoordinated with the national PV system. However, the national
immunization program in Bangladesh reported collecting 1,100 adverse events reports
following immunization in 2011 against a patient population of 3.7 million children
vaccinated. A review of Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund)
grants for round 10 shows that Cambodia and Thailand included activities or interventions
related to PV in their disease specific or health systems strengthening grants. Though disease
surveillance activities are in place, active safety surveillance of medical products was very
limited. Other components of the PV system including risk management and communication
were minimal or lacking in all five countries.
Pharmacovigilance at the Service Delivery Level

A total of 86 health facilities and 62 pharmacies were surveyed across the five countries.
Only a quarter of the private or community pharmacies surveyed are aware that a national
PV center exists in their country. Nearly half of the community pharmacies were aware of a
national policy for monitoring and reporting adverse events. However, less than half of the
health facilities surveyed have adverse events reporting form available. In Nepal, Thailand,
and the Philippines a quarter of facilities surveyed reported that they had received medicines
safety bulletins from their national PV centers.
Pharmacovigilance in the Pharmaceutical Industry

The assessment included five clinical research organizations (CROs), seven medical
device companies, and 38 pharmaceutical companies, including multinational innovator,
multinational generic and local innovator and generic manufacturers. Sixty-six percent of
pharmaceutical companies, 57% of medical device companies, and 80% of CROs have a PV
or medicine safety unit. The pharmaceutical industry PV performance is below expectation
in an already weak regulatory environment. More than one third of pharmaceuticals,
biotechnology and medical device companies do not submit adverse events reports in
national standard forms or in E2B compliant formats. Among the companies included in the
assessment, it was found that less than half of pharmaceutical companies (42%) and just more
than half of medical device companies (57%) collected spontaneous adverse events reports,
put them in a database, and transmitted to the local NRA. In 2011, causality was determined
for only a third of the reports. Risk assessment and evaluation and risk management practices
are not being implemented presumably since they are not explicitly required in country laws.
Pharmacovigilance at the Civil Society Level
Ten consumer groups, 22 professional organizations, and 21 medical and pharmacy academic
institutions were surveyed in this group, members from three (30%) and eight (36%)
respectively serve on the national safety advisory committee in Bangladesh, Cambodia,
and the Philippines. Few respondents (20% in consumer group and 27% in professional
associations) reported that consumers and members of their association were aware of the
existence of a national policy for monitoring and reporting adverse events. About half of the
professional associations reported having a member who is aware of the national PV center
The while only 20% of consumer groups reported that this knowledge exists among patients and
pharmaceutical consumers.
industry’s PV Capacity and Performance of PV Systems in the Studied Countries
performance
Countries were grouped based on the systems classification; of the five countries, Bangladesh
is below and Nepal are in group 1 with minimal organizational structures and capacity for PV,
expectation Cambodia is in group 2 with policy and legal frameworks, basic organizational structures
in an already including guidelines, SOPs, and a safety advisory committee. Philippines is in group 3 which
weak regulatory are countries that have capacity to collect and evaluate safety data on the basis of legal and
environment. organizational structure and Thailand is in group 4 for countries that have performing PV
systems to detect, evaluate, and prevent medicine safety issues.
Selected Recommendations and Options for

Enhancing PV Systems
National Level
Strengthen Regulatory Policies and Framework
Based on the level of development of regulatory and PV systems, countries can develop new
regulatory policies and frameworks to ensure that regulations are effective and in the public
interest or revise and consolidate the existing ones. Alternatively they can review sections
of existing legislation that deal with aspects of medicines quality, safety, and post-marketing
surveillance, ensure that legislations are congruent with other relevant local laws.
Ensure Convergent Regional and International Regulations

Options for countries for developing regulations convergent within the Asian region—map
differences and provide guidance on regulations that the country considers as equivalent to
regional and international standards or develop guidance to industry to explicitly document
regional equivalencies or countries can completely revise their PV legislation to make them
convergent with that of stringent regulatory authorities and also consistent with the regional
harmonization guidelines within the Asia Pacific region and other international guidelines.
Improve Information Sharing and Participation in Regional

Harmonization Initiatives
Asian regional harmonization initiatives should consider strengthening collaboration and
information sharing about product safety and security of the supply chain by ensuring active
participation of the all countries in the region.
Reform Organizational Structure to Achieve Integrated Safety Surveillance
Countries can create a single vigilance center that can facilitate the integration of adverse
events reporting for all health products or consolidate post-marketing surveillance
department that brings together PV, product quality surveillance, routine inspections, and
control of advert and promotion into a single unit.
Improve Funding for PV

Countries should consider reviewing resource allocation for regulatory activities and
determine an evidence-based approach for allocating adequate resources for post-marketing
surveillance activities. Alternatively new sources of funding can be explored including donor
funding, user fees and percentage of sales turnover.
Strengthen Spontaneous Reporting

Countries should adopt international reporting standards and explore opportunities for
the use of information technologies for improving adverse events reporting. Countries
should also explore opportunities to consolidate or streamline reporting forms for all health
products (drugs, biologics, vaccines, and medical devices) and for reporting on all safety and
quality issues.
Confront Falsified and Substandard Medicines

Donors and technical assistance providers should consolidate their support to expand WHO
and regional harmonization initiatives rapid alert system as major instruments for addressing
the issues of falsified and substandard products. Countries should be supported to improve
their regulatory systems and enforcement capabilities for addressing fake products.
Public Health Programs Level

Strengthen Routine Collection of Information on the Tolerability of Medicines
Countries should encourage routine documentation of the reasons for treatment switches
in the patient’s case file which will provide data for studying the frequency of switches and
tolerability treatment regimens.
Develop Sustainable Risk Assessment and Evaluation Activities

Countries should explore opportunities for establishing sentinel sites for active surveillance
by working closely with ART, TB, malaria, vaccines, and mass drug administration programs.
Include PV in Donation Programs

Donors who donate medicines and health technologies should require their programs to
conduct spontaneous reporting, active surveillance, and risk management, particularly for
newer medicines, vaccines, and medical devices.
Health Facilities and Services Delivery Level

Inform Health Workers on the Value of PV
Countries should expand training on PV to enable health workers appreciate the contributions
of adverse events reporting in safeguarding patients and improving treatment outcomes.
Streamline Adverse Events Reporting
The current adverse events reporting system is burdensome for the busy clinicians and the
system does not motivate the reporter. Countries should consult with stakeholders in open
forums to discuss on the best approaches for improving the roles of health workers, the
health facilities, private pharmacies, consumers, and pharmaceutical industry in adverse
events reporting.
Pharmaceutical Industry
Medicine Strengthen Industry Commitment to PV
safety systems The pharmaceutical industry is not doing enough to support PV activities in the countries
within and studied. In the absence of adequate legislation and enforcement in developing countries,
across national due diligence and product stewardship should drive the industry to meet safety monitoring
borders requirements locally as they do in better regulated markets.
need to be Collaborate on Device Regulation and Vigilance
strengthened.
Medical device industry should collaborate with national regulatory authorities and regional
harmonization initiatives to develop device vigilance systems.
Civil Societies
Improve the Visibility of PV as a Public Health Priority
Civil society’s active involvement in PV systems depends not only on awareness of the
legal mandate, structures and systems for PV in the country but also on the society’s
understanding of its importance and how drug safety affects their members. Civil societies
should motivate their members interest in PV as part of its role as the watchdog for good
governance in the pharmaceutical sector.
Conclusion
Strengthening the regulatory and PV system of the studied countries is a global imperative
for preventing harm and improving outcomes in treatment and prevention programs and
for protecting the global supply chain from falsified and substandard medicines. There is
a strong and urgent need to strengthen medicine safety systems both within and across
national borders of countries in the Asia region. Developing and developed countries are
both suppliers and recipients within an increasingly complex global medical product supply
chain. Public health programs, global health initiatives, and indeed, entire health systems rely
on safe, effective, and good quality medicines. However, fully functional PV and regulatory
systems are not yet in place in many LMICs. This report calls for concerted efforts to build
regional and global coalition and leverage ongoing efforts in a consolidated manner to
improve the systems and capacities required to assure patient safety and to improve health
outcomes in Asia.
Introduction
Background on Asian Pharmaceutical Market

Asia has an estimated 4.2 billion inhabitants, representing nearly 60% of the world’s total
population. China and India together account for 37% of the world population and 61%
of Asian population, with the remaining being dispersed among the other 46 countries
that make up the continent. Southern Asia and Southeast Asia constitute about 54% of the
Asia population. The 5 countries in this report belong to the two regions and have a total
population of 359.7 million, about 16% of the regions’ population. Asia region is characterized
by vast discrepancies in wealth and development. The gross domestic product (GDP) per
capita of the continent’s poorest country, Nepal, is equivalent to just 2% of Singapore’s,
the continent’s wealthiest country. In the Human Development Index ratings, four Asian
countries are among the top 25 countries with “very high human development” while five
others are among those with “low human development.” The pharmaceutical market profiles
of the five countries included in the present assessment—Bangladesh, Cambodia, Nepal, the
Philippines and Thailand—reflect some of the same diversity seen throughout the region
(table 1). The populations range from 150.5 million in Bangladesh to just 14.3 million in
Cambodia. All of them are considered low- or middle-income countries with Nepal on the
low end with a GDP per capita of 619 US dollars (USD) as compared to Thailand, an upper
middle income country, with a GDP per capita of USD 4,972.
Figure 1. Map of Asian Countries Included in Assessment
Nepal TAIWAN
CHINA
BHUTAN
Bangladesh
VIETNAM
MYANMAR
INDIA
(BURMA) LAOS Philippines
Thailand
Cambodia
SRI LANKA BRUNEI
MALAYSIA
INDONESIA
introduction 19
Table 1. Summary of Pharmaceutical Market in Studied Countries
Pharmaceutical market Bangladesh Cambodia Nepal Philippines Thailand
Population (million; 2012)* 154.7 14.9 27.5 96.7 66.8
Gross domestic product 744 900 619 2,370 4,972
per capita (USD)*
Market size: 1.5 billion 178 million Not available 2.91 billion 4 billion
pharmaceuticals (USD,
2011)†
Market size: medical 174 million 27 million Not available 297 million 1.11 billion
devices (USD, 2011)†
Number of medicines 32,245 10,000 (est.) 10,316 32,069 24,087
registered (2011)‡
Number of medical devices Not available 2410
registered (2011)
Total expenditure on 19 29 29 77 179
healthcare per capita
(USD, 2010)§
Total pharmaceutical 5.7 9.3 4.7 21.3 70
expenditure (TPE) per
capita (USD, 2006)§
Public expenditure on Not available 1.3 0.9 2.1 42.5
pharmaceuticals per capita
(USD, 2006)§
TPE as % total expenditure 31 21 16 28 39
on healthcare per capita
(2006)§
Health workforce per 0.21 10.8 16.1 10.2 physicians; 3 physicians;
10,000 population|| 53.1 nurses/ 15.2 nurses/
midwives; midwives;
5.4 licensed 1.2 pharmaceutical
pharmacists; personnel
11.0 pharmaceutical
personnel
Financing mechanisms for Public (11%), Public (14%), Public (19%); Public (10%), Public/ Public (88%),
pharmaceuticals§ Private/Other Private/ Other Private/Other Other (90%) Private/Other (12%)
(89%) (86%) (81%)
* World Bank Database: http://data.worldbank.org
† Business Monitor International: Bangladesh Q1 2013 (January 1, 2013), Cambodia Q4 2012 (October 1, 2012), Philippines Q1 2013 (January 1, 2013), Thailand Q1 2013
(January 1, 2013)
‡ Directorate General of Drug Administration (Bangladesh); Cambodia MOH DDF; WHO Nepal Pharmaceutical Market (http://apps.who.int/medicinedocs/en/m/abstract/
Js19096en/); Directorate General of Drug Administration (Philippines); Thai FDA, 2011;
§ Estimates derived from several WHO sources including World Medicines Situation 2011 Annex, Pharmaceutical Sector Country Profiles Data and Reports, and National Health
Accounts.
|| WHO World Health Statistics 2012
Figure 2. Pharmaceutical Market Size of Asian Countries in Assessment
Pharmaceutical Market Size

200 Bangladesh (billion USD, 2011)
1.50 bn
150 Philippines
Population (million, 2011)
2.91 bn
Thailand
4.41 bn
100
Nepal
50
0.14 bn
Cambodia
0.18 bn
0
USD 0 USD 2,000 USD 4,000 USD 6,000
GDP per capita (USD, 2011)
The Asian pharmaceutical market size is estimated at USD 140 billion, with China and
Japan accounting for about 70 percent of the total value. Most of the market is dominated
by generic medicines, although Japan and Singapore have a strong patented medicine
market, especially for chronic diseases. Of the countries studied, Thailand has the largest
pharmaceutical market size with over USD 4.4 billion and Nepal has the smallest with USD
1.4 million. Vietnam has the fastest growing healthcare market in Southeast Asia, with more
than 200 pharmaceutical companies registered that produce mostly generic medicines.1 In
the Philippines, foreign drug companies account for 70 percent of the market. There are over
3500 pharmaceutical brands marketed with the main therapeutic categories including anti-
infectives, antihypertensives, and analgesics.1
Regarding burden of disease, the Southeast Asian region accounts for about 30% of the global
disease burden (Dhillon et al. 2012). In Asia and the Pacific, an estimated 6.1 million people
were living with the human immunodeficiency virus (HIV) in 2009, 5.9 million of whom
were adults. Although the epidemic is decreasing overall, the burden of HIV and AIDS
remains high, especially in some countries like Thailand, which has the highest rates of HIV
and AIDS in the Asia region (UNAIDS 2010). Tuberculosis (TB) also represents a major
health problem in Asia. In fact, 60% of incident cases of TB globally in 2011 were in Asia
(WHO 2012a). Although the incidence of malaria has decreased in the region over the last
decade, there are still an estimated 30 million cases in Asia each year. This burden is further
exasperated by increasing evidence in Southeast Asia of emerging resistance to artemisinin-
based combination therapy, the recommended treatment for malaria (WHO 2012b).
Definition and Scope of Pharmacovigilance

The World Health Organization (WHO) defines PV as the science and activities relating
to the detection, assessment, understanding, and prevention of adverse effects or any other
possible drug-related problems (WHO 2004). PV systems should include all entities and
1 http://www.pacificbridgemedical.com/business-services/pharmaceutical-consulting/
introduction 21
resources that protect the public from medicines-related harm (adverse reactions, poor
product quality, medication errors, and therapeutic ineffectiveness), whether in personal
healthcare or public health services. The PV system safeguards the public through efficient
and timely identification, collection, and assessment of medicine-related adverse events
and by communicating risks and benefits to support decision making about medicines at
various levels of the healthcare system. A comprehensive systems approach addresses the
need for both active and passive approaches to identify medicines-related problems, effective
mechanisms to communicate medicine safety information to healthcare professionals and the
public, collaboration among a wide range of partners and organizations, and incorporation
of PV activities at all levels of the health system (Strengthening Pharmaceutical Systems
(SPS) Program 2011). Several multinational organizations and initiatives work on defining the
standards of PV.
The WHO has provided technical and normative leadership on PV since the development
of the first voluntary notification scheme in 1961. The WHO International Drug
Monitoring program has more than 111 countries participating as of January 2013. WHO
has defined norms and guidelines for PV and allow for information sharing among the
participating countries. Another WHO PV-related activity is the work of the Council for
International Organizations of Medical Sciences (CIOMS) which was established jointly
by WHO and UNESCO in 1949. Starting with the publication of the Suspect Adverse
Reaction Report Form (CIOMS Form I) by the CIOMS working group II, other CIOMS
publications have greatly shaped the direction of PV.2 CIOMS publications have also
greatly influenced the development of International Conference on Harmonization of
Technical requirements for Registration of Pharmaceuticals for Human Use (ICH) E2A-
E2F guidelines in drug safety. The standards for the electronic transmission of regulatory
information regarding the individual case safety report (ICSR) has been changing over
the last decade. The ICH adopted the E2B(R2) in February 2001 and since 2005 the
E2B(R3) is being developed as the proposed harmonized international standards for
health products safety reporting. This effort led by International Standards Organization
(ISO) and Health Level Seven International (HL7) has led to the development of ISO/HL7
27953-1:2011. These ICH guidelines have facilitated the adoption of harmonized standards
for PV activities.
In 1999, the ICH formed the Global Cooperation Group (GCG) to promote a mutual
understanding of regional harmonization initiatives to harmonization process related to ICH
guidelines regionally and globally, and to facilitate the capacity of drug regulatory authorities
and industry to use them. Part of the result of the work of the GCG and the open availability
of harmonized guidelines from the ICH, is the increasing adaptation of ICH standards in
non-ICH countries.
With regards to medical devices vigilance, the Global Harmonization Task Force (GHTF) use
to set the standards for their regulation. However, the GHTF activities have been taken over
by the International Medical Device Regulators Forum (IMDRF) formed in 2011. The GHTF
SG2 guidelines on Medical Devices Post Market Surveillance: Global Guidance for Adverse
Event Reporting for Medical Devices provides harmonized standards for monitoring safety
of medical devices (European Commission 2013). The EU guidelines on reporting adverse
2 Including CIOMS II on periodic safety update reports (PSUR), CIOMS III core data sheets, CIOMS IV on bene-
fit-risk assessments, CIOMS V on Current Challenges in Pharmacovigilance: Pragmatic Approaches, CIOMS VI on
clinical trials safety data, CIOMS VII on development safety update reports (DSUR), and CIOMS VIII on Practical
Aspects of Signal Detection in Pharmacovigilance.
events related to medical devices is set out by MEDDEV 2.12/1 rev.8 (European Commission
2013) and by MEDDEV 2.12/2 rev.2 (European Commission 2012) which promote a standard
approach consistent with the SG2 guidelines. Table 2 below summarizes the functions of
these various initiatives.
Table 2. Functions of Select PV Initiatives

Organization Initiative/Program Function
WHO International drug monitoring §§ Defines norms and guidelines for PV and
program facilitates information sharing among
participating countries
§§ WHO Collaborating Centre for
International Drug Monitoring runs the
international monitoring program
CIOMS Safety requirements for the use of §§ Through 8 Working Groups CIOMS has
drugs defined technical standards in drug
safety
ICH, GCG Pharmaceutical standards §§ Facilitates harmonization process related
harmonization and guidelines to ICH guidelines regionally and globally
development
GHTF, IMDRF International medical device §§ Harmonizes the standards for
regulatory harmonization and monitoring the safety of medical devices
convergence
introduction 23
Study Objectives
and Methods
Objectives
This study contributes to filling the gap in the understanding of the PV systems capacity in
Bangladesh, Cambodia, Nepal, the Philippines and Thailand by addressing the following
objectives—
Assess and analyze systems capacity and performances for PV and post-marketing
surveillance
§§ Identify successful and replicable experiences to further enhance medicines safety and
quality systems
§§ Map out how donor agencies and local/regional/global health efforts are contributing
to PV
§§ Recommend options for enhancing PV and post-market surveillance systems capacity
and performances
Study Methods
The following methods were used to conduct the study—
1. Review of regulatory and PV systems

2. Individual country assessments
3. Comparative analysis of results from individual country studies
1. Review of Regulatory and PV Systems

We conducted a detailed review of regulatory and PV systems literature using key search
terms in drug regulation and PV. We also reviewed databases from WHO, ICH, and searched
commercial regulatory intelligence databases from Thomson Reuters. We searched the
websites of regional harmonization initiatives, and also reviewed websites of regulatory
authorities from the United States, Europe, Japan, Australia, Canada, China, South Korea,
Saudi Arabia, India, Malaysia, Singapore, and Indonesia, and all the five countries studied.
2. Individual Country Assessments

Local consultants led individual country assessments using the indicator-based PV
assessment tool (IPAT) developed by the USAID-funded Strengthening Pharmaceutical
Systems (SPS) Program. The IPAT allows for the systematic and longitudinal monitoring of
country capacity and performance in ensuring the safety and effectiveness of health products
registered in a country (Strengthening Pharmaceutical Systems (SPS) Program 2009a). The
local consultants were identified by the national regulatory authorities. Working with a team
of data collectors, the local consultants conducted in depth data collection in each country
between April and November 2012.
s t u dy o b j e c t i v e s a n d m e t h o d s 25
Selection of Study Countries
Not much is known about PV systems in South Asia and Southeast Asian countries and
there is scant literature that compares countries’ PV systems from a regional perspective.
This study included countries from the two regions. The countries were selected based on
several factors including economic status, the existence of global and regional public health
initiatives (i.e., the President’s Emergency Plan for AIDS Relief [PEPFAR], the President’s
Malaria Initiative [PMI], and the Global Fund), manufacturing capacity, the size of the
pharmaceutical industry, and the existence of a National Drug Regulatory authority.
Other selection criteria included the existence of WHO prequalified quality control (QC)
laboratories, WHO international drug monitoring program membership, participation in
initiatives to combat counterfeit and substandard products, and Management Sciences for
Health presence. Using these criteria, several countries qualified for the study. From the
South Asia region we excluded India since the study did not have the resources to cover a
country of that size. Several countries in the two regions presented logistical challenges that
could not be overcome by the available funding for the study. Five countries were eventually
chosen for the study—Bangladesh, Cambodia, Nepal, the Philippines, and Thailand and in-
depth assessment of the PV systems was conducted in those countries
The summarized version of the description of the study method is included in annex E in this
document. Further details on the selection of study sites within each country, recruitment
of consultants and data collectors, data entry, limitations, and results of the study are in the
individual country reports (Stergachis A, Rahman Md M 2012; Men C 2012; Shresta NP 2012;
Marcelo J 2013; Sakulbumrungsil R 2013).
3. Comparative Analysis of Results from Individual Country Studies

The data from the individual country assessment was collated and entered into a database
developed for the purposes of the study based on the five PV components namely
Governance and Policy, Law, and Regulation; Systems, Structure, Stakeholder Coordination;
Signal Generation and Data Management; Risk Assessment and Evaluation; and Risk
Management and Communication. A rating scale was applied to classify the performance
of each component area within the study countries’ PV systems. Based on the scoring of the
five components of the PV system in the data collection tool, specific strengths and gaps in
each component were identified. Tables and bar charts were used to compare performance of
indicators within the same component. Radar charts were used to illustrate the performance
in each component. Qualitative information from the literature reviews were used to
supplement the quantitative data collected through the individual country assessments.
Review of Regulatory and
As access to medicines improves, the value of strengthening PV systems is becoming

increasingly recognized. However, PV systems in many countries are not well described. The reason for
Most Asian drug safety literature focuses only on adverse event reporting. Books on Asian pharmaceutical
regulatory systems mainly address PV regulations in China, India, Japan, and Singapore
regulation is
(Klincewicz S, Yap Y 2009; Gillespie J 2009) and do not discuss the medicines safety systems
to ensure
in any depth. Also there is no documentation of how PV systems contribute to improved
treatment outcomes. The review discusses significant medication safety events that have the safety of
impacted on regulatory reforms, the importance of PV, and recent efforts at international health products
cooperation and harmonization for sharing safety information. and protect
public health.
Medication Mishaps Have Catalyzed Medicines Regulation
Historically, development of medicines regulation has been catalyzed by medication mishaps.
Harm from the use of medicines can be a consequence of manufacturing error, product
falsification, intrinsic toxicity of the product, and unsafe use (by prescribers, dispensers, and
patients). The death of 107 people in 1937 from elixir of sulfanilamide contaminated with
diethylene glycol, and the severe malformations, primarily phocomelia, in about 10,000
children which occurred from 1956 to 1962 in mothers who were exposed to thalidomide
during pregnancy, were defining drug safety events that spurred regulatory actions. The
diethylene glycol case led to the enactment of the Federal Food, Drug, and Cosmetic
Act (1938) and in reaction to the thalidomide cases, the WHO developed the voluntary
notification scheme in 1961. The fundamental reason for pharmaceutical regulation is to
ensure the safety of health products and protect public health.
In Asia, medication mishaps have led to public concerns and calls for strengthening
regulations. In 2005, a sophisticated investigation into fake artesunate suggested that the fake
antimalarial drugs were killing millions (WHO estimates 20% of the one million malaria
deaths per year is from fake products). The investigators identified two trafficking networks,
one from the Thai-Myanmar border and northern Laos and the other from southern Laos,
Vietnam, and Cambodia. Three people were arrested for trafficking 240,000 blister packs of
fake artesunate into Myanmar (Newton et al. 2008) containing no or subtherapeutic amounts
of the active antimalarial ingredient, which has led to deaths from untreated malaria, reduced
confidence in this vital drug, large economic losses for legitimate manufacturers, and
concerns that artemisinin resistance might be engendered.
The 2008 heparin related deaths and allergic reactions in the United States were attributed to
economically-motivated adulteration of heparin with over-sulphated chondroitin sulphate
from Baxter’s Chinese heparin supplier. A total of 131 heparin-related deaths were reported
to US Food and Drug Administration (FDA) between January 1, 2007 and April 13, 2008.
In 2012, the then Chinese State Food and Drug Administration shut down more than 80
manufacturing lines in Zhejiang, seized more than 77 million capsules, and arrested 22 people
r e v i e w o f r e g u l ato ry a n d p h a r maco v i g i l a n c e s ys t e m s 27
in connection with chromium-laced capsules of medicines, including many antibiotics.
Medication mishaps and corruption coupled with a vision to strengthen local industry has
resulted in several changes in the Chinese regulatory systems leading to the reorganization
and consolidation of the powers of the State Food and Drug Administration into a
ministerial-level agency, the China Food and Drug Administration (CFDA). Similarly, in
India a parliamentary committee audit of the Central Drugs Standard Control Organization
(CDSCO) argued that the organization is facilitating the development of the drug industry to
the detriment of public health. The committee found that the CDSCO approved marketing
of 13 drugs including dipyrone which did not have permission for sale in any of the major
developed countries and also approved clinical trial for fixed-dose combination of aceclofenac
with drotaverine, a combination not in use in developed countries (Parliament of India 2012).
Subsequently another committee recommended that a Special Expert Committee should be
set up that should be independent of the Drug Technical Advisory Board to review all drug
formulations in the market and identify drugs which are potentially hazardous and/or of
doubtful therapeutic efficacy (Chaudhury expert committee 2013). In Pakistan, the death of
125 patients in 2012 who received a cardiac drug contaminated with an antimalarial medicine
lead to the Pakistani government quickly establishing a central Drug Regulatory Authority
in 2012. This case underlined the need to address the jurisdictional confusion created by the
passage of the amendment that decentralized public health.
Recognition of Importance and Practice of Pharmacovigilance

Adverse reactions, poor product quality, medication errors, and therapeutic ineffectiveness
waste resources and have devastating impact on the health systems by leading to treatment
failure, drug resistance, loss of confidence in the health system, and increased morbidity and
mortality. Adverse drug reactions are the fourth–sixth leading cause of death (Lazarou 1998)
and patients who experienced adverse drug events (ADEs) were hospitalized an average of 8
to 12 days longer than patients who did not suffer from ADEs and their hospitalization cost
USD 16,000 to USD 24,000 more.
The overall objective of a NRA for medicinal products is to ensure that all medicines,
medical devices, vaccines, blood products, and other biologicals are of assured quality,
safety and efficacy and are accompanied by appropriate information to promote their safe
use. Regulatory authorities are responsible for making decisions regarding label changes
(dose, indication, etc.) or variation in marketing authorization, drug safety alerts, control
of unapproved claims, prescription to over-the-counter status switch and vice versa, and
product withdrawal or recalls. Though the enactment of new regulations has been the main
tool by governments and the regulators to prevent subsequent harmful occurrences and
protect public health, the understanding of how to protect the public health is still evolving.
From recognizing the need to demand safety, quality, and efficacy before medicines are
introduced in the market, national regulatory authorities also developed surveillance and
enforcement units to monitor the market and ensure that products maintain their quality
and safety after approval. However, efforts to secure the market have not been completely
successful with the continued availability of substandard and falsified medicines in the
supply chain of most countries. The development of PV and post-marketing surveillance
systems is a strategy that could be used to supplement information gathered prior to
market authorization. According to the US Institute of Medicine (IOM), preapproval
clinical trials do not obviate continuing formal evaluation after approval (IOM 2007).
Clinical trials for the authorization of new medicines usually focus on determining
efficacy of the product in limited number of persons, typically with narrowly defined
characteristics, for a short duration of time. Like in developed countries the importance
of PV is well recognized amongst the regulatory authorities in the Asia region. Most of
the countries regulatory organizations have maintained a post-marketing surveillance or
PV unit as a part of their agency’s structure. Countries in the region are participating in
the WHO international drug monitoring program. The table below shows the current
membership status for Asia.
Table 3. WHO-UMC Membership Status

Official member Associate member Non-member
Brunei Darussalam (2005) Bhutan Afghanistan
Cambodia (2012) Mongolia Bangladesh
China (1998) Pakistan Korea, Dem. Republic
India (1998) Lao PDR
Indonesia (1990) Myanmar
Japan (1972)
Korea, Rep. (1992)
Malaysia (1990)
Nepal (2006)
Philippines (1995)
Singapore (1993)
Sri Lanka (2000)
Thailand (1984)
Vietnam (1999)
Early members of the WHO drug monitoring program like Japan, Thailand, Indonesia,
and Korea have well developed spontaneous reporting systems. Korea and Thailand are in
the top 10 countries in the WHO Global ICSR database (Uppsala Monitoring Center 2013).
Many of the official members have more developed regulatory systems with surveillance
and enforcement units, newer members and non-member countries are beginning to put
these structures in place. Notwithstanding PV practices in the region vary tremendously.
A review of the regulatory requirements shows different reporting timelines and different
reporting forms and requirements for electronic submission, PV inspections and audits,
etc. Sharing of information on regulatory decisions vary as well. While many NRAs in the
region barely communicate their regulatory action, Singapore HSA in 2011 issued more
than 280 decisions related to safety of medicines and Indonesia Badan Pom and Malaysia
National Pharmaceutical Control Bureau provides opportunities for consumers to report
health products complaints online. In their quest to protect the public and also answer tough
questions on the products they allow on the market, regulators are challenged to develop
strategies for improving the safety of products. Several strategies additional to spontaneous
reporting systems have been incorporated including requirements for the conduct of risk
management, post-authorization studies, and review of the benefit-risk throughout the
product life-cycle. These practices are not very common among regulatory authorities in
the region.
International Collaboration and Harmonization

Securing the supply chain from unsafe products in any country is a challenge no regulatory
authority can now confront alone. To help PV achieve its intended purpose, international
collaboration and information sharing is required. International collaboration in regulatory
activities can help to reduce duplicative testing of products, clinical trials, and inspections.
Timely information sharing between regulatory authorities can be helpful in addressing
outbreaks of substandard, falsified, and unsafe medicines, and is a condition for securing
the global supply chain. With growing globalization of drug development, complexity of
the products, and global economic challenges, the need for harmonization or at least some
convergence of standards and requirements is increasingly being recognized. Thus, the
International Conference on Harmonization of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) was launched in 1990 to develop technical guidelines
for product registration to harmonize standards and reduce duplication. The ICH has
developed over 50 guidelines including the guidelines that cover the reporting and evaluation
of data on safety and efficacy of pharmaceutical products in pre- and post-approval periods
(drug safety guidelines E2A to E2F). Also supporting ICH work are the M2 guidelines that
facilitate the electronic standards for the transfer of regulatory information (ESTRI), the
Medical Dictionary for Regulatory Activities (MedDRA) terminology, and the Common
Technical Document. Besides Japan, a founding member of the ICH, Asia regulators are at
different stages of adoption of international standards and guidelines developed by the ICH.
The need for sharing of regulatory information is recognized and the adoption of common
standards is improving.
Comparison of Pharmacovigilance Practices of Stringent Regulatory

Authorities and Asia Reference Authorities
The European Medicines Authority (EMA) is the authority responsible for coordinating PV
systems in the European Union (EU). Regulation EC 726/2004 calls for intensive supervision
of undesirable effects of medicinal products within the framework of community PV
activities and rapid withdrawal of products presenting a negative risk-benefit balance under
normal conditions of use. In the United States, the reporting of adverse events is mandated by
law for the product sponsors. The regulations governing drug safety are covered by Title 21 of
the Code of Federal Regulations. Title IX of the Food and Drug Administration Amendments
Act (FDAAA) of 2007 provided FDA with enhanced authorities regarding post-market safety
of drugs.
PV activities in the EU and United States have continued to change and evolve as the public
asks for greater transparency and protection (Health Action International 2008; Wolfe 2006).
The EMA posts the European Public Assessment Report (EPAR) in their website, the FDA
posts the products approval package on its website Drugs@FDA, and the Japan PMDA posts
the review reports for approved products on its website. Provided in the table 4 below is
some comparison of key features of the drug safety system across the stringent regulatory
authorities (SRAs) of EU, United States, and Japan alongside the practices in China, India,
and Singapore.
Regional Harmonization Initiatives in Asia

The Asia Pacific Economic Collaboration (APEC) set up the Regulatory Harmonization
Steering Committee (RHSC) with the aim to promote a more strategic, effective, and
sustainable approach to regulatory convergence by proactively identifying and prioritizing
projects of greatest value to regulators and the regulated industry. One of RHSC’s
harmonization topics is on PV—the Korea FDA is the lead agency. Through this work group,
the steering committee strives to address regulatory harmonization in PV. The roadmap for
strengthening PV systems is currently being developed. The Asian Harmonization Working
Party (AHWP) activities are focused on the medical devices. The AHWP was established
to study and recommend ways to harmonize medical device regulations in Asia and other
regions and to work in coordination with the Global Harmonization Task Force, APEC,
and other related international organizations (Asian Harmonization Working Party 2010).
Table 4. Comparison of Drug Safety Systems Across SRAs
Regulatory Stringent NRAs Asian competent/reference NRAs

requirements EMA US FDA Japan China India Singapore
PV regulations Regulation FD&C Act Pharmaceutical Drug Drugs and Medicine Act
EC 726/2004; 1938; FDA Affairs Law; Administrate- Cosmetics Act Chapter 176,
Directive Modernization MHLW Ordinance tion Law 1984; 1940; Drugs 1977
2010/84/EU; Act 1997; FDAAA No.135 of 2004; Regulations for and Cosmetics
Regulation (EU) 2007; FDASIA GVP and Good Implementation Rules 1945
1235/2010; EU 2012; 21 CFR Post-Marketing of Drug (Schedule Y)
Vol. 9A Study Practice Administration
(GPSP) Law 2002
Mandatory Yes
industry reporting
of serious ADRs
Clinical trials Yes Yes Yes Yes Yes Yes
register exists? (EudraCT) (clinicaltrials. (JapicCTI) (ChiCTR) (CTRI) (HSACTR)
gov)
Monitoring period Yes Yes Yes Yes No
for new drugs (5 years)* (5 years) (4–10 years) (5 years)
required
Expedited Yes (15 days)
reporting of
serious ADRs for
marketed drugs
required
PV Inspections and Yes No
audits required
Risk management Yes Yes Yes No No (however
plans (RMP) (RMP) (REMS) (GPSP) applications
mandated should include
RMP or REMS)
Spontaneous Eudra-Vigilance FDA Adverse ADR information National ADR Vigiflow provided No
reporting database Event Reporting management Monitoring by UMC is used
exists System (FAERS), system System under Pharmaco-
VAERS database vigilance Program
of India (PvPI)
Periodic safety Yes (every 6 Yes (every 3 Yes (every 6 Yes (annually for Yes (every 6 Yes (every 6
update reports months for the months for first 3 months for the the first 5 years) months for the months for the
required first 2 years) years) first 2 years) first 2 years and first 2 years)
(frequency) then annually
thereafter, but
applicable only
to “new drugs,
until 4 years after
launch”)
Active surveillance EU-ADR project, Sentinel system MIHARI project No
initiative ENCePP,
PROTECT
Identified person Yes (QPPV) No Yes (Safety Yes (PMR rules) No Yes
responsible for PV Control Manager,
mandated† SCM)
* The EMA has a black triangle scheme that will come into effect in the last quarter of 2013. The scheme requires that black inverted triangle should be displayed in the package
leaflet of new medicines and denotes that the medicine is under intense additional monitoring.
† Industry is mandated to have someone responsible for PV. An example is the Qualified Person for Pharmacovigilance (QPPV) in Europe.
ENCePP- European Network of Centres for Pharmacoepidemiology and Pharmacovigilance
MIHARI - Medical Information for Risk Assessment Initiative
PMR- Administrative measures for monitoring and reporting of ADRs, 2004
QPPV- Qualified Person in Pharmacovigilance
PROTECT- Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium
Seventeen member economies including Cambodia, Philippines, and Thailand are AHWP
members. Recently, the AHWP was accepted as a member of the International Medical
Devices Regulators Forum.
Cambodia, Philippines, and Thailand are also members of the Association of Southeast
Asian Nations (ASEAN). The ASEAN Economic Community (AEC) Blueprint identifies
standards and conformance as one of the technical areas for harmonization. The blueprint
includes the objective to strengthen post market surveillance systems to ensure the
successful implementation of the harmonized technical regulations (AEC 2008). One of
ASEAN’s working groups is the Pharmaceutical Product Working Group that serves as the
regional harmonization initiative. The initiative aims to develop ASEAN member countries
harmonization schemes of pharmaceutical regulations to complement and facilitate the
objectives of the ASEAN Free Trade Area (AFTA), particularly the elimination of technical
barriers to trade posed by regulations without compromising product quality, efficacy, and
safety. To facilitate this regional harmonization effort, the Pharmaceutical Product Working
Group has identified mutual technical areas including GMP inspection, bioavailability and
bioequivalence standards, and post-marketing surveillance. ASEAN countries participate in a
post-marketing alert (PMA) system. The objective of the PMA system is for ASEAN member
countries to share information relating to defective or unsafe cosmetics, health supplements,
traditional medicines, and pharmaceutical medicinal products. In the event of a major safety
concern that results in a recall or withdrawal, the PMA system can be used to notify the
various regulatory agencies in a timely manner (Rahman E 2008).
A similar PMA framework has also been developed for medical devices. Some of the
region’s countries have limited capacity for medical device regulation. In the absence of
adequate regulation, adverse events are not reported and when products cause harm, there
is little in the way of corrective action and product recalls. So implementing the PMA for
medical devices can help address some of these gaps in those countries that have limited
device regulatory capacity. Under the PMA arrangement, the countries are harmonizing
terminologies, standards, and reporting timelines; they also are developing systems
for the use of common reporting forms and the sharing of information on quality and
safety of products in the ASEAN market. In a report on the activities of the system it was
identified that non-steroidal anti-inflammatory agents were the most commonly reported
adulterants (45.8%). Most of the anti-inflammatory agents could have been manufactured
by countries within the region or members of the regional harmonization initiative thereby
providing an opportunity to deal with the problem from a regional level. An analysis of the
Cambodia national medicines register showed that 89% of registered products (table 5) are
manufactured in countries from the region.
Table 5. Countries of Manufacture of Cambodia Registered Products

Total # of products in the Cambodia national register 10,636
Country of manufacture of products # of products Registered products, %
India 6,163 58
Thailand 1,604 15
Bangladesh 573 5
Philippines 197 2
Others 2099 20
Total 10,636 100
Bangladesh and Nepal are members of the eight member group, the South Asia Association
for Regional Cooperation (SAARC). Working on strategies for the establishment of common
standards or harmonization of regulatory requirements for pharmaceuticals has not been
discussed by this group. However, during the 2005 SAARC Third Ministerial Conference on
Health, attendees requested the Technical Committee on Health and Population to prepare
a plan of action in the areas of medical expertise and pharmaceuticals, harmonization of
standards and certification procedures; and increased production of affordable medicines as
well as traditional medicines. It is not clear how things have progressed in the work of this
technical committee since then.
SAARC members established the South Asian Regional Standards Organization to develop
harmonized standards to facilitate intra-regional trade and to have access to the global
market. Its Sectoral Technical Committee collaborates on harmonization in the areas of
food and agricultural products, textiles, and quality management (Spanta RD, Chowdhury
IH, Tshering U, Mukherjee P, Shahid A, Mahat RS, Qureshi MSM 2008). Pharmaceutical-
related issues have never been addressed and could be a potential area to bring the members
together to set standards on medicines regulatory harmonization. The lessons learned
from the other regional harmonization groups like APEC and ASEAN in building the
infrastructure for achieving convergence of standards, mutual recognitions, and sharing of
regulatory information are important for the SAARC as well. Table 6 provides the regional
harmonization initiatives, whether they work on pharmaceuticals and medical devices or not,
and the countries that are members.
Table 6. Regional Harmonization Initiatives Member Countries

Regulatory harmonization initiatives (RHI)
Acronym of the RHI APEC APEC ASEAN SAARC
Working group/committee RHSC AHWP PPWG SARSO
Pharmaceuticals/medical
devices part of harmonization ü ü ü
Participates in GCG ü ü
Country membership
Bangladesh ü
Cambodia ü ü
Nepal ü
Philippines ü ü
Thailand ü ü ü
Poor Quality Products

Poor quality products constitute major public health concern in the Asia region. Of 1437
samples of drugs in five classes from seven countries in Southeast Asia, 497 (35%) failed
chemical analysis, 423 (46%) of 919 failed packaging analysis, and 450 (36%) of 1260 were
classified as falsified (Nayyar et al. 2012). When substandard, adulterated, or falsified
medicines are used treatments fail, drug resistance can occur (in the case of anti-infectives),
and patients can be directly harmed from the products toxic effects. In many low and middle-
income countries the need to protect the public from the adverse events associated with sub-
standard and falsified products by eliminating them from the supply chain is a major concern
among health officials as well as consumers. Detection of product quality problems, harm
from the use of unsafe products and actions taken by governments to extract substandard
and falsified products from the market and punish offenders have been reported in
developing countries across all regions (Promoting the Quality of Medicines Program 2013;
Dorlo et al. 2012). In the region China and India have been mentioned as sources of poor
quality products, though a government sponsored report in 2009 put the level of spurious
drug in retail pharmacy in India at only 0.046% (CDSCO 2009). An IOM report suggests
that information such as the number of doctor’s appointments repeated because of falsified
A comprehensive and substandard drugs, the number of hospital beds occupied by victims of pharmaceutical
and sustainable crimes, premature deaths from untreated disease, and productive years lost to society from
QA system medicine poisoning can be generated by PV. When PV systems detect problems related to
is needed to the safety, efficacy and quality of medicines, the opportunity exists for these signals to be
prevent, detect, followed up more thoroughly. In-depth investigations can eventually produce data on the
specific consequences, including magnitude and cost, of falsified and substandard medicines
and respond to
(Institute of Medicine 2013).
substandard
pharmaceutical Countries need a comprehensive and sustainable quality assurance system that prevents,
detects, and responds to the presence of substandard pharmaceutical products in circulation.
products.
A quality assurance system is comprised of the structures, functions and processes, including
both managerial and technical activities that monitor the quality of pharmaceuticals
throughout all stages of the product cycle, from production to use. PV is part of such a
system, but alone is not sufficient. Quality assurance includes inspections for compliance
with GMP, assessment of documentation on product quality submitted by manufacturers
for registration as well as procurement, sampling and testing of pharmaceutical products
from the market and other entry points and systematic evaluation of reported product
quality problems through the PV system (Alghabban 2004). Many international, regional
and national efforts have been launched to address the issue of substandard and falsified
products through improved information sharing and are yielding good results for the benefit
of patients. On the international level, WHO-UMC regularly publishes a document called
SIGNAL, which contains medicine safety signals representing varying levels of suspicions,
including suspected product quality concerns, based on the Center’s analysis of the data
submitted by countries worldwide into the WHO Global Individual Case Safety Reports
database. Another initiative that can advance product quality information sharing in the
region is the WHO Western Pacific Region (WPRO) rapid alert system as a vehicle for
addressing the issues of falsified and substandard products. Regionally in Southeast Asia,
the use of the PMA system by the ASEAN pharmaceutical product working group has been
noted above. Individual countries can benefit greatly from information sharing on product
quality issues at the international and regional levels, if they use information that is deemed
relevant and applicable to the pharmaceuticals in their market to make regulatory decisions
and take appropriate actions. Through information sharing, problems can be prevented or
detected early, which not only saves money but also has the potential to save lives.
Challenges for Pharmacovigilance Systems in Asia

The lack of harmonized regulatory approach and differences in safety reporting requirements
in the region is one of the major obstacles to PV in Asia. Another challenge is the inability
of the current regulatory system to safeguard public health from incidences of falsified and
substandard products in the market in the region. When the functions and operations of the
regulatory authorities are reviewed or audited by government accountability offices, often the
central question is to determine the regulatory impact and effectiveness of the strategies in
place for safeguarding public health. Other challenges for regulatory and PV systems in the
region include how to generate and share reliable data that can be used for timely benefit and
risk decision making. The ability to collect data on real-life effectiveness will contribute to
efforts to understand the benefits and risks of medicines. Inability to take timely regulatory
decisions to protect public health is a challenge across developing countries. Products
that are withdrawn by SRAs are available in the region. In most cases the NRAs have not
reviewed the continued usefulness of the products nor provided reasons lack of regulatory
action. Advocates for improved access to medicines in LMICs countries use a metric called
drug lag—to indicate how long it takes before an essential medicine licensed by SRAs is The lack of a
introduced by developing countries (Wardell 1973, Andersson 1992, Olson 2013). At the other harmonized
end of the drug lag is the safety lag—how long it takes for developing countries to react to a regulatory
regulatory action taken by SRAs for a product that is also marketed in their country. One of approach and
the new challenges of PV is to reduce safety lag globally. The harmonization of standards, use differences in
of common terminologies, and sharing information can help reduce safety lag and reduce
safety reporting
continued exposure to harmful products. PV in the Asia region has to prove its utility and
return on investment, for instance, reduction in medicines-related mortality and morbidity. requirements is
Asia can also use PV data to determine therapeutic gaps and define goals for new medicines. one of the major
Using data on real-life safety and effectiveness will make it possible to define the limitations obstacles to PV
of existing medicines in terms of therapeutic failure, toxicities, adherence challenges, in Asia.
inconvenient formulations, and abuse potential, and use this information to define what is
required of the ideal medicine for that indication.
Comparative Analysis of
Results of Assessment of
Pharmacovigilance at the National Level

The comparative analysis of the results of the PV systems in Bangladesh, Cambodia, Nepal,
the Philippines and Thailand is presented in this section of the report. At each of the five key
stakeholder groupings — national level (including the ministry of health and NRAs); public
health programs (HIV and AIDS, TB, malaria, vaccine and immunization program, and mass
drug administration); health facilities and service delivery level; pharmaceutical industry;
and civil societies level, we reviewed and compared countries performance using the
relevant indicators from the five components of a comprehensive PV system (1. Governance,
Policy, Law, and Regulation, 2. System, Structure, and Stakeholder Coordination, 3.
Signal Generation and Data Management, 4. Risk Assessment and Evaluation, and 5. Risk
Management and Communication).
co m pa r at i v e a n a lys i s o f r e s u lt s o f a s s e s s m e n t o f p h a r maco v i g i l a n c e s ys t e m s 37
Governance, Policy,
Law, and Regulation
Governance
Countries were regarded as performing well in the area of governance if the following
indicators were addressed—
§§ Existence of regulatory framework

§§ Existence of regulatory registries
§§ Governance structures mandated by the legislation/regulations and in practice
Existence of Regulatory Framework

All countries assessed were found to have at least some description of their regulatory
framework. These were either defined by the national pharmaceutical policies or the
pharmaceuticals sector strategic plans. The frameworks typically describe means for
achieving objectives mandated by pharmaceutical legislation and regulations. For Cambodia
and Nepal, the regulatory framework is not explicitly described.
Existence of Regulatory Registries

All countries have registers for products, licensed pharmaceutical premises, and licensed
pharmaceutical personnel in place. Bangladesh, Cambodia, Nepal, Philippines, and Thailand
have their product registers readily available through the NRA website, though some of these
were only available in the local language, outdated, or only available in a database format
that cannot be easily downloaded or tabulated. Investing in maintenance of record-keeping
systems allows regulatory authorities to streamline workload and improve governance
and transparency by making up-to-date information on medical products and regulatory
activities more readily accessible to stakeholders.
Governance Structures Mandated by Regulations and in Practice

According to WHO, governance is a process of decision making and the process by which
decisions are implemented (or not implemented); it involves ensuring that there is a
strategic policy framework, effective oversight, coalition-building, regulation, attention
to system-design, and accountability and the recognition that governments should
operate in a transparent and accountable manner with high regard for rule of law (Anello
2008; WHO 2009). All countries have at least some governance structures within the
pharmaceutical system that were mandated by legislation and regulations, including systems
for accountability, transparency, and legislative enforcement. The assessment measured the
extent to which these governance structures were implemented and in practice as mandated.
Bangladesh, the Philippines, and Thailand reported having had an evaluation of regulatory
systems within the past five years and a government accountability audit conducted within
the last one year. Both Nepal and Cambodia reported existence of governance structures;
however, neither has had an audit or evaluation to determine the extent to which they are
g o v e r n a n c e , p o l i c y , l aw , a n d r e g u l at i o n 39
implemented and enforced. Of the five Asian countries, three (Bangladesh, Philippines, and
Thailand) were found to have key attributes of a functioning governance system in place,
including the existence of a regulatory framework, regulatory registries, and governance
structures (table 7).
Table 7. PV Governance at the National Level

Bangladesh Cambodia Nepal Philippines Thailand
Regulatory framework ü * * ü ü
Regulatory register ü ü ü ü ü
Governance structures
mandated and in ü * * ü ü
practice
* Exists but not assessed or fully in place
Policy, Law, and Regulation

Essential Statements on PV or Medicines Safety in National Policy
All countries surveyed have a National Medicines Policy (NMP) that address medicine safety.
The NMPs contain requirements for ensuring product quality assurance (QA) (at a minimum
Good Manufacturing Practices [GMP] inspection) and provisions for the control of medical
product advertising and promotion. The Philippines has a specific national PV policy.
Legal Provision for PV in the National Medicines Legislation

All countries assessed have national medicine laws in place that include legal provisions
broadly related to medicine safety. However, the regulatory requirements for pre- and post-
marketing surveillance activities are found in different laws and are not always aligned with
each other. The Philippines has a detailed inventory of its food and drug laws and regulations
including the National Policy and Program on Pharmacovigilance (“Food and Drug
Administration Philippines”). Cambodia specifically mentions PV in the legislation. Laws
and regulations provide the legal basis for conducting medicines safety activities in a country,
with regulations guiding implementation and enforcement of the law.
Provisions That Mandate Market Authorization Holders to

Conduct Post-Marketing Surveillance
Cambodia, the Philippines, and Thailand, were found to have legal provisions mandating
pharmaceutical industry to report suspected adverse events to the National PV Center.
However, the PV requirements, where they exist, are not always consistent with international
standards and vary greatly across the countries. Only the Philippines mandates that industry
conduct post-marketing surveillance of specified products based on stringent regulatory
authority requirements. The Philippines also requires a three-year initial registration prior
to being eligible for application and approval for general use. This program is regarded as
monitored release of a new medicine. In Thailand, the Safety Monitoring Program (SMP)
mandates that the industry monitor the safety of new medicines for two years.
Table 8. Content Analysis of PV Regulatory Requirements for the
Pharmaceutical Industry in Two Countries
Regulation Philippines Thailand
Sections of laws and regulations Republic Act section2 l of Drug Act B.E. 2510 (1967)
related to safety of medicines† 3720; Republic Act No. 7394; Section 86, 91
FDA Circular No. 201 3-003
Industry reporting of serious ADEs
mandated (expedited reporting ü ü
required)
§§ Reporting timelines for 7 days 24 hours (for fatal outcomes),
marketed products (serious) 7 days (unexpected with fatal
outcome) and 15 days (other
serious AEFI/ADR)
§§ Reporting timelines for Quarterly, 30th of first month 60 days
marketed products
(non-serious)
Periodic safety update reports
required ü every 6 months ü (for selected products)
§§ Reporting timelines
§§ Reporting timelines for clinical
7 days 7/15 days
trials (SUSAR)
-- Fatal/life threatening 24 hours
Monitoring period for new
medicines required ü 3 years ü 2 years
ü Checkmark denotes that the regulation is required in the country
† For Philippines, this is specified in the FDA Circular No. 201 3-003, not specified for Thailand
Legal Provision for Product Quality Assurance

All countries were found to have at least minimum legal provisions for the quality
assurance of medicines in their national laws and regulations (table 9). To ensure
the quality of products, legal provisions in a country should address product quality
standards relating to manufacturing, importing, exporting, wholesale, distribution, storage,
dispensing, and retail sales.
Table 9. Content Analysis of Pharmaceutical Legislation

Legal provisions for product
quality assurance Bangladesh Cambodia Nepal Philippines Thailand
Laws/regulations that require GMP ü
inspection ü ü (imports)
ü ü
WHO prequalification and Certificate
of Pharmaceutical Product (CPP) Not mandatory n/a ü ü ü
referenced during the registration
Requirement that a GMP certificate
is issued to manufacturers of ü No ü Not mandatory ü
pharmaceutical products
Laws/regulations to ensure that
donated products are registered and ü ü ü ü ü
inspected
Guidelines for Good Distribution
Practices in place ü ü No Drafting Drafting
Case Study 1. The Safety Monitoring Program (SMP) in Thailand
Post-marketing surveillance is particularly relevant for medicines identified as high-risk or with
unknown or incomplete safety profiles among the general population or in certain high-risk
groups such as pregnant women, children, the immune-compromised, and the elderly. The
safety profile of new medicines at the point of market introduction is incomplete. In 1991,
Thailand’s Food and Drug Administration (FDA) began implementing the Safety Monitoring
Program (SMP) to monitor the safety of new medicines. SMP is intended to confirm the safety
of new medicines in Thai patients by generating earlier safety signals and gathering more
safety information before granting unconditional registration approval. It monitors all new
medicines, including products with new chemical entities, new indications, new combinations,
and new delivery systems. Under SMP, the Thai FDA grants conditional approval for registration
of new medicines for a period of two years. Products with conditional status must have a
blue triangular emblem displayed on the product packaging and can only be distributed
through hospitals or healthcare facilities under the close supervision of physicians. During the
two-year safety monitoring period, reporting of adverse drug reactions is mandatory for the
pharmaceutical companies seeking full marketing authorization (Wibulpolprasert 1999). At
the end of the two years, pharmaceutical companies must submit comprehensive summary
reports to the Thai FDA, which may include reports of adverse drug reactions (ADRs), drug
consumption, and detailed drug experiences from other countries where the product has been
used. Drug products with no evidence of serious adverse events or with benefits that outweigh
its risks will receive unconditional approval. The market authorization holders are then allowed
to distribute the approved products through regular channels (Amrumpai et al. 2007).
Legal Provision for Control of Promotion and Advertisement

All countries in the assessment were found to have laws in place controlling the promotion
and advertisement of medicines (table 10). The actual content of the legislation or the degree
of their enforcement was not determined, however. NRAs should have legal provisions and
guidelines to ensure that statements made about medical products through advertising
and promotional activities are accurate and correspond to approve product information,
including clinical indication and use. NRAs are responsible for providing independent, non-
promotional information on medicines to the public and healthcare providers. Authority
should be granted to NRAs to take regulatory action against industry found to be in
violation of the legal provisions, recognizing the risk to patient safety posed by incomplete or
misleading information and the potential for such information to strongly influence the way
that medicines are purchased and used. NRAs should have ethical guidelines in place that
adhere to the WHO Ethical Criteria for Medicinal Drug Promotion guidelines and serve as
authoritative sources (HAI Global 2010).
Discussion
Governance involves ensuring that there is a strategic policy framework, effective oversight,
coalition-building, regulation, attention to system design, and accountability and the
recognition that governments should operate in a transparent and responsible manner with
high regard for rule of law (Anello 2008; WHO 2009). The existence of governance systems
and structures that promote transparency and accountability within national regulatory
authorities, including policies, laws and regulations, provide a fundamental platform for
effectively regulating the safety, quality, and effectiveness of health products, safeguarding
public health, and promoting pharmaceutical sector trade and economic growth. Regulatory
Table 10. Summary of Policy, Law, and Regulation
PV or medicines safety
policy ü ü ü ü ü
PV or medicine safety
in national medicines ü ü ü ü ü
legislation
MAH mandated by
law to report serious
adverse drug reactions ü ü ü*
to NRA
MAH required to
conduct post-market
surveillance per ü
stringent regulatory
authority standards
Legal provision for
product quality ü ü ü ü ü
assurance
Legal provision
for promotion and ü ü ü ü ü
advertisement
* SMP mandatorily requires the industry to monitor the safety of new medicines for 2 years
frameworks define countries’ pharmaceutical regulation and governance, and include

legislation, policies, guidance documents, and other governance instruments that collectively
define how pharmaceuticals are regulated. Establishing regulatory registers is the first step
in the process to define what is allowed in the market. The registers, depending on type
(product register or list of registered pharmacies, premises, etc.) should contain minimum
sets of information. For instance, WHO recommends that minimum information should
include generic name, dosage form, strength, trade name, marketing authorization holder,
authorization number, indications, status (new chemical entity [NCE] or non-NCE [WHO
2011]). Registers can facilitate information sharing and increases transparency if publically
available (WHO 2010a).
One of the most important elements in the regulatory framework is pharmaceutical

legislation, which includes statutory laws and regulations to guide enforcement activities.
The framework for most countries also defines and delineates the mission and strategic
objectives of the regulating authorities, their functions, the scope of products they regulate,
and the outcome of their activities, typically measured in terms of promoting access and
protecting public health. Many regulatory bodies have challenges in meeting the public
expectations and defining stakeholders’ roles in advancing access while avoiding medical
mishaps. For instance, the legal requirements for the industry should be clearly stated in
the law. International standards, such as the ICH guidelines (International Conference on
Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human
Use) and practices of stringent regulatory authorities including the European Medicines
Agency (European Medicines Agency 2012) and US FDA, require MAH to report serious
adverse events wherever their products are marketed. They also may require post-marketing
surveillance or risk mitigation activities for products with significant unresolved safety
concerns or for high-risk medicines. Without the necessary legal provisions in place, the
safety of medicines cannot be adequately monitored; laws and regulations provide the
legal foundation for conducting and enforcing a country’s medicines safety activities with
regulations guiding how laws are implemented.
According to WHO, NMP should contain several elements relating to medicine safety,
including requirements for establishing PV systems and developing legislation and regulations
for monitoring the safety of medicines (WHO 2004). Additionally, NMPs should include
provisions related to product quality assurance and control of promotion and advertising.
Such essential statements on PV may also appear in other documents, including public health
program (PHP) policies or treatment guidelines. An approved national PV or medicines safety
policy is the guiding document that provides the authority and mandate to monitor medicine
safety and take appropriate regulatory action. To complement the policy, PV guidelines
provide operational direction and standards for implementing activities, such as spontaneous
reporting of adverse drug reactions (ADRs), active surveillance, provision of medicine
information, and delineation and coordination of stakeholder roles and responsibilities.
Systems, Structure, and
Stakeholder Coordination
PV Center or Unit with a Clear Mandate, Structure, Roles,

and Responsibilities
All countries had a national PV center or unit in place operating under the Ministry of
Health’s medicines regulatory authority and a staff member dedicated to PV within their
centers. The national PV centers in Cambodia, Philippines, and Thailand had clear and
documented mandates, structures, and scopes of work in terms of roles and responsibilities;
whereas in Bangladesh and Nepal, the mission, vision, and function were not explicitly
documented. Nepal has plans to update its NRA organizational structure to include
the national and regional PV centers. Further review of the structure of the PV centers
showed that the mandate, structure, and scope of activities varies across the countries
and opportunities for leveraging expertise and resources throughout the NRA for safety
monitoring are not exploited. The Thailand Health Product Vigilance Center (HPVC) has
expanded its mandate to monitor the safety of all health products.
Budget for PV
Thailand reported having a dedicated annual budget for PV-related activities (table 11) and
receives dedicated annual funding to cover its operations.
Table 11. Funding for PV Activities in Five Countries

Dedicated budget
available for
PV-related activities Bangladesh Cambodia Nepal Philippines Thailand
Annual budgetary
allocation for PV Limited* ü
activities or PV center
Funds provided by MoH
or donors toward PV ü ü Limited* ü
activities in 2011
* WHO-UMC dues only
Part of the PV funding that is available for countries is from the Global Fund. A review of
Global Fund grants for round 10 shows that Cambodia and Thailand, have included activities
or interventions related to PV in their disease specific or health systems strengthening (HSS)
grants (table 12).
s ys t e m s , s t r u c t u r e , a n d s ta k e h o l d e r co o r d i n at i o n 45
Table 12. Grants to Support PV
Country Global Fund grants for PV
Bangladesh No
Cambodia Yes
Nepal No
Philippines No
Thailand Yes
Quality Control Lab (or Unit) with Clear Mandate, Structure,

and Functions
All five countries have quality control laboratories; however, only Thailand (WHO 2013a) has
WHO pre-qualified quality control laboratory facilities (table 13).
Table 13. Availability of Quality Control Lab Services in Five Asian Countries
Existence of quality
control lab (or unit) with
clear mandate, structure
and functions Bangladesh Cambodia Nepal Philippines Thailand†
QC lab (or unit) under the
NRA or affiliated with the ü ü ü ü ü
NRA
Functions of QC lab
a, b, c, d, e a, c, d, e a, c, d, e a, b, c, d, e a, b, c, e
include?
QC lab have a
documented quality ü ü Drafted ü ü
management system*
QC lab is prequalified by
the WHO ü
QC lab has been audited
in the past ü ü ü
five years
a. Testing of pharmaceuticals (non-biological products)
b. Testing of biological products such as vaccines
c. Participation in registration activities
d. Inspection of industry quality control labs
e. Collaboration with the Inspectorate to test collected samples
* based on ISO 17025
† Accessed the WHO Public Inspection Report of the BDN http://apps.who.int/prequal/WHOPIR/pq_whopir.htm
National PV Guideline/National Standard Operating Procedures

for PV and QC
Cambodia and Thailand have national PV guidelines in place. In the Philippines, the
national PV policy also serves as the guidelines. The Philippines and Thailand both
reported existence of standard operating procedures (SOPs) for PV and QC, though a
document was not available for verification. Bangladesh and Nepal had neither guidelines
nor SOPs for PV or QC. Further content review showed that national guidelines are
limited to the notification system for passive reporting of suspected adverse drug
reactions. Typically, the existing guidelines did not cover other PV methods like active
surveillance and did not address other PMS activities like product quality surveillance,
risk management, and control of advertisement and promotion.
Medicines Safety Advisory Committee and Quality Control
Advisory Committee
All but one of the countries, Thailand, reported the existence of a Medicines Safety Advisory
committee that meets regularly (at least once within the past year) and has a documented
decision-making process. The Philippines’ 2011 PV policy calls for an advisory committee;
however, the committee has not yet been formed. Only Thailand has a Medicines Safety
Advisory Committee with policies addressing conflict of interest and a mandate for reviewing
safety concerns associated with clinical trials. Both Thailand and Cambodia reported
existence of fully functional Quality Control Committees that have met at least once in the
last year.
PV Medicines Information Service

All countries report that the PV center addresses medicines safety inquiries.
Core Communication Technologies for PV/Core PV Reference

Material in PV Unit/Drug Information Center
The assessment found that with the exception of Bangladesh, all countries reported the
presence of basic communication technologies for medicine safety including phone, fax,
internet, e-mail, computers, and software for databases that record regulatory activities like
information requests received and addressed, safety alerts released, and newsletters planned
and published. Except for Bangladesh and Cambodia other countries have basic medicine
safety reference materials on hand within the national PV center to address medicine safety
requests.
Core PV Topics in Pre-Service Training Curricula

The assessment found that, within each of the countries studied, at least one of the academic
institutions sampled is providing instruction on PV topics.
PV Stakeholder Coordination Mechanism

All countries listed the national PV center as the recognized and established mechanism
responsible for coordinating PV stakeholders in their country, except for Bangladesh where
the PV center had been established but has limited capacity to coordinate. The assessment
found that the PV centers had limited success connecting with all relevant stakeholders and
engaging them to participate fully in medicine safety and prevention activities, as evidenced
by the absence of adequate representation in committees; relatively low rates of AE reporting
by healthcare providers, industry and consumers; and, the limited reach of medicine
information communication strategies.
WHO International Drug Monitoring Programme Membership

Cambodia, Nepal, the Philippines, and Thailand are official members of the WHO
International Drug Monitoring Programme. Thailand joined as an official member in 1984,
followed by the Philippines in 1995, Nepal in 2006, and Cambodia in 2012 (WHO 2013b).
Bangladesh intends to apply for associate membership to the Programme in 2013.3
3 Personal communication with the Bangladesh Directorate General of Drug Administration, November 2012.
Quality Management System for PV and Quality Assurance
The assessment found that, although all countries address quality management issues
within their NRAs, only the Philippines have a formal quality management system in
place addressing PV and quality assurance. The Philippines FDA also has an agency-wide
quality management system (QMS). Inspectors conduct PV inspections and as of the time
of assessment have conducted 41,030 audits. However, the QMS may not be adequate for
performing PV and quality assurance activities. As noted previously, Thailand has a QMS
based on ISO 17025 for their quality control laboratory.
Thailand introduced a Performance Management and Quality Assurance system within

national-level agencies, including the Thai FDA that monitors quality through key
performance indicators (World Bank 2012), though the assessment found that the system is
not focused specifically on medicine safety and PV within the Thai FDA or Thailand’s HPVC.
Below is a summary of the country assessments for the PV component of systems, structure,
and stakeholder coordination (table 14).
Discussion
National PV centers can serve as the coordination point for conducting PV activities in a
country. However, the current structure of those centers fragments the related post-market
surveillance and overall safety monitoring functions. Across all the countries assessed, the
current system does not exploit opportunities for leveraging expertise and resources. PV
centers function optimally with a dedicated budget, at least one full-time staff member
(WHO recommends at least one part-time staff member (WHO)), a clear mandate
and organizational structure, and well-articulated roles, responsibilities, and reporting
requirements. Countries that lack PV center and basic infrastructure and capacity will not be
able to reach timely informed decisions to protect their populations from the untoward and
harmful effects of medications.
National quality control laboratories serve an important role in ensuring quality testing
and detection of falsified and substandard medicines. Without these systems, patients and
communities may be exposed to ineffective and toxic products that can lead to undesirable
or even fatal consequences. However, countries do not seem to consider quality and safety
issues in whole but rather across the different units of the regulatory authority and close
collaboration between the regulatory units was not evident. Countries need medicine quality
control laboratories in place to ensure appropriate testing and examination of products
(Strengthening Pharmaceutical Systems (SPS) Program 2009b). Moreover, countries should
aim at obtaining the WHO prequalification for their national labs, which means that the
laboratory is in conformity with the standards recommended by the WHO for medicines
quality control (Strengthening Pharmaceutical Systems (SPS) Program 2009b). Also for
adequate functioning of national PV and quality assurance activities there is a need for
guidelines and SOPs. National guidelines serve as the basis for structured and coordinated
actions, according to established standards, by the various stakeholders within a PV system.
They explain and support compliance with existing medicine safety laws, regulations,
and policies in a country. In all the countries studied, the PV guidelines contain only
basic information on the passive surveillance notification system and nothing on active
surveillance. The guidelines addressed identification of spontaneously reported adverse drug
reactions and do not include other sources of product-related harm, such as poor product
quality, medication error, inappropriate advert and promotion. They also do not articulate
the roles of all stakeholders and the need for collaborated efforts at addressing issues related
Table 14. System, Structure, and Stakeholder Coordination at the National Level
System, structure, and stakeholder
coordination Bangladesh Cambodia Nepal Philippines Thailand
PV center or unit ü ü ü ü ü
PV center/unit has clear mandate, structure,
function ü ü ü
QC lab/unit with clear mandate, structure,
function ü * * ü ü
PV information service ü ü ü ü ü
Dedicated staff for PV ü ü ü ü ü
Budget for PV ü
Up-to-date National Guidelines for PV ü ü
SOPs for PV and quality control † ü ü
Medicine safety advisory committee ü ü
Quality control committee ü ü
Core communication technologies for PV ü ü ü ü
Core PV reference material in PV center/drug
information center ü ü ü ü
Core PV topics present in the pre-service
training curricula ü ü ü ü ü
Healthcare workers trained on PV and medicine
safety ü ü ü ü ü
PV stakeholder coordination mechanism ü ü ü ü
WHO Programme for International Drug
Monitoring Membership ü ü ü ü
Quality management system for PV and quality
assurance ü ü
üIndicator is met by the country
* Exists but not assessed/audited or fully in place
† SOP for QC only,
Blank cells denote that the assessment was unable to confirm the status of the indicator
to product safety. SOPs help stakeholders to implement guidelines and to standardize

medicine safety functions operations within the regulatory authority. Thus, it is crucial that
all countries develop and implement comprehensive guidelines and SOPs for PV activities.
To support national PV centers in meeting their mandate, multidisciplinary advisory

committees are required. WHO recommends that medicines advisory committees
include members from related scientific disciplines, including general medicine, clinical
pharmacology, toxicology, epidemiology, pathology, drug regulation and quality assurance,
and drug information (WHO 2000). The committees support PV centers and NRAs with the
collection and assessment of medicine safety data, evaluation of risk, and communication
of medicine safety decisions and information. There is also movement to have consumers
represented on advisory committees through inclusion of patient groups or civil societies
active in promoting access and safe use of pharmaceuticals. Consumer representation on
medicine safety advisory committees is advised as a means of fully addressing and engaging
patients in the national PV system.
The responsibility for PV should be shared among multiple stakeholders within a country,
including drug regulators, the pharmaceutical industry, PHPs, health service delivery
providers, civil society, international technical institutions (such as WHO), regional
cooperation bodies, donor organizations and the public. Many countries have had
limited and fragmented interactions and coordination efforts among stakeholders. Yet, a
coordination mechanism is needed to know exactly what is happening where and when
and who is doing what. This will allow an efficient use of resources and avoid duplication.
Regular mapping of stakeholders, meetings with representative stakeholders, and defining
pathways of collaboration between parties involved can contribute to this coordination. The
WHO Programme for International Drug Monitoring is a global network that provides a
mechanism for members to collaborate and build their capacity in PV so that early signs of
medicine safety issues can be identified, information about them can be effectively shared,
and appropriate actions can be taken on a global level. Membership in the program gives
countries access to a database of worldwide medicine safety information, early information
about potential safety hazards, data tools, and technical resources for PV (support, trainings,
and guidelines). The membership requires that country must be a WHO member state;
country must have a program for collection of ICSRs in place; country must have a national
PV center recognized by the MoH; country has to demonstrate that it is capable of submitting
data in the required format; a sample of at least 20 ICSRs collected in the national PV
program should be submitted to the UMC (WHO 2010b).
Except for Bangladesh, all countries studied reported that they have core communication
technologies to support their PV activities. Investments in communication technology and
medicine safety reference materials within NRAs is necessary for national PV centers to
receive, collate, and disseminate locally relevant medicine information and safety reporting to
healthcare providers, consumers, industry, and other stakeholders.
Basic medicine safety reference materials help ensure that national PV centers have access
to and can make full use of current and accurate medicine safety information to address
medicine safety inquiries or generate safety communication materials and alerts. Countries
may use the list of recommended core reference material for PV to benchmark their medicine
safety information resources (annex F). The assessed countries are all doing well in ensuring
that core PV topics are taught in pre-service programs and that health worker are trained
in PV. The integration of locally relevant and contextualized PV topics into pre-service
and in-service education for healthcare providers is vital to prepare them and refresh their
knowledge and skills.
Because PV is a cross-cutting issue that touches on many disciplines, components of PV

can be integrated into various existing courses and training programs. Public education on
responsible and informed medicine use and attention to medicine safety are equally vital
for a comprehensive approach to supporting the medicine safety system. Countries may
refer to the list of PV topics to develop training materials for current and future healthcare
professionals (annex F).
Signal Generation
and Data Management
Systems for Coordination and Collation of PV Data from all Sources

within a Country
With the exception of Bangladesh, all countries surveyed have a national database in place
for collating ADR data and transmitting data to the WHO International Drug Monitoring
Programme (table 15).
Table 15. PV Data Management

Existence of a system
for coordination and
collation of PV data
from all sources in the
country Bangladesh Cambodia Nepal Philippines Thailand
Local database system
for collating PV data ü ü ü ü
from all sources
Method by which
reporting forms are Post/in
Post,
typically collected and Post Electronic Electronic* person,
electronic
transmitted to PV center electronic
or unit
PV data transmission
comply with E2B format ü* ü* ü* ü
Standard dictionaries
and terminologies used
to transcribe reported ü* ü* ü* ü
events (i.e., WHO-ART,
MedDRA)
* Via VigiFLow, the WHO-UMC ICSR management system; blank cells denote that the indicator is not met in that country
The system for the collation of PV data should enable a country to review submitted reports,
identify missing data, and generate basic aggregate reports. The assessment also reviewed the
data mining methods used by the different countries (table 16).
s i g n a l g e n e r at i o n aanndd data
data ma ageemmeenntt
mannag 51
Table 16. Data Mining Methods Used in the Study Countries
Country Method used
Bangladesh Not available
Cambodia BCPNN*
Nepal BCPNN
Philippines BCPNN
Thailand ROR†
* BCPNN: Bayesian confidence propagation neural network (this is the WHO method and countries rely on the analysis done by
the WHO)
† ROR: reporting odds ratio
Though four countries have database systems for collating PV data from all sources, none had
a centralized data warehouse for storing adverse events reports from all sources including
spontaneous reports through the passive surveillance system, active surveillance data or
reports, periodic safety update reports (PSURs), and development safety update reports
(DSURs). Bangladesh has not fully adopted ICH E2B format or the CIOMS I form for the
reporting of adverse events.
Existence of a Form for Reporting Suspected ADRs

All countries surveyed were found to have a standardized national AE or suspected ADR
reporting form that is designed to collect basic adverse event information. However, these
forms were limited in their availability within service delivery points. Only 35 of 86 health
facilities (41%) and 13 of 62 pharmacies (21%) sampled across five countries reported
existence of an ADR form within their facility. Availability of ADR forms within industry
was also limited: the assessment found that 23 of 38 pharmaceutical companies (61%), 4 of 7
medical device companies (57%), and 2 of 5 clinical research organizations (40%) studied had
an ADR form available.
Low rates of ADR reporting are a serious challenge in Nepal, Cambodia, and Bangladesh. The
contents, format, and transmission requirement of the reporting forms vary greatly across
the countries; some require the reporter to determine seriousness, causality, and electronic
transmission
The assessment found that Thailand and Philippines both have national ADR reporting
forms that collect data on product quality issues, and medication error, and treatment failure.
Table 17. Signal Generation and Data Management at the National Level
National PV data
collation system ü ü ü ü
Consumer
reporting form ü ü
Suspected ADR
reporting form ü ü ü ü ü
Product quality
Medication error
Treatment failure
Thailand has a consolidated form for the reporting of all suspected adverse events and for all
health products.
Both Thailand and the Philippines have a separate and simplified consumer reporting form
for suspected ADRs. Dissemination of the consumer reporting form to the service delivery
level remains a challenge, particularly in Thailand, where none of the health facilities and
pharmacies sampled was found to have the reporting form available. In the Philippines, only
3 of the 20 pharmacies studied (15%) had the form available, although it was found in almost
half of the health facilities (11 of 23, 48%).
Discussion
The generation of safety signals is critical to detecting potentially harmful medical products,
and taking appropriate regulatory action. Detecting and reporting of adverse events is
the first step in a comprehensive and continuous PV monitoring process. WHO defines a
medicine safety signal as “reported information on a possible causal relationship between
an adverse event and a drug, the relationship being unknown or incompletely documented
previously” (WHO 2000). Managing data once it is generated is equally important to allow
safety risks to be evaluated, causality to be determined, and regulatory action to be taken in a
timely manner. When a signal arises from one or more sources, particularly a potential signal
that has significant public health importance, it should be further investigated. This process is
essential both to ensure that harmful medical products are avoided and that safe and effective
products remain in use.
Although countries had reporting forms available for ADR, optimal safety data reporting was
affected by the low availability of reporting forms in points of service, the lack of forms to
report medication error, deficient product quality, and treatment failure, and underreporting
of adverse events by health professionals. Except for Thailand, in the other countries the
reporting system for ADRs and product quality are separated and so is the reporting system
for medical devices and vaccines separated from those of other health products.
Case Study 2. One Form for All Events in Thailand

In Thailand, the HPVC has developed one reporting form for suspected adverse events to
all health products including medicines, drug/narcotics and psychotropic substance, food,
cosmetic, medical device, and hazardous substance. The scope of adverse events covered by
the form is adverse reactions, product quality, medication error, and treatment failure. The form
is also a very good example of using a single form for spontaneous, intensive, and clinical trial
reporting. While being consistent with international ICH E2B standards, the form’s checklist
format promotes adverse events reporting by requiring minimal written information which
facilitates easy reporting.
The use of a consolidated form for the reporting of all suspected adverse events of health
products is an emerging idea at the international level. This effort led by ISO and HL7 has
led to the development of ISO/HL7 27953-1:2011 as an ISO standard for data exchange and
information sharing.1
The opportunities for the development of this consolidated form in Thailand may not be
unconnected to the overarching mandate of its HPVC to monitor the safety of all health
products.
1 Individual case safety reports (ICSRs) in pharmacovigilance. http://www.iso.org/iso/home/store/catalogue_tc/catalogue_
detail.htm?csnumber=53824
s i g n a l g e n e r at i o n a n d data ma n ag e m e n t 53
Risk Assessment
and Evaluation
Number of Spontaneous Reports

Significant underreporting was observed in all countries, with the exception of Thailand.
Table 18 provides the number of reports received by country in 2011.
Table 18. Actual ADR Reporting versus Expected

Expected (200 ADR
No. of ADR Population reports per million
Country reports (2011) (million, 2011)* population)† % of Expected
Bangladesh 0 150.5 30,100 0
Cambodia 83 14.3 2,861 3
Nepal 35 30.5 6,097 1
Philippines 3,351 94.9 18,970 18
Thailand 57,573 69.5 13,904 414
* World Bank Database, Accessed September 10, 2012 http://data.worldbank.org/country http://data.worldbank.org/country
† The WHO Programme for International Drug Monitoring recommends that in relation to ADR reporting, the optimal National
Pharmacovigilance Centre should send over 200 reports per million inhabitants per year http://who-umc.org/DynPage.aspx?id=1
08476&mn1=7347&mn2=7252&mn3=7322&mn4=7558
Only Thailand met and exceeded the WHO requirement for optimal National
Pharmacovigilance Centre to produce 200 reports per million population (WHO). Practices
that may have contributed to this success include the adoption of the number of ICSRs as a
performance indicator for health facilities by the Thailand National Health Security Office,
the PV promoting activities of the Adverse Drug Reaction’s Community of Pharmacy Practice
(ADCoPT) which have provided a platform for reinforcing the need for reporting among
pharmacists, and the Thai FDA implementation of the SMP.
Cambodia and Thailand conducted causality assessments on more than half of the adverse events
reports generated through passive surveillance activities. This allowed for the further assessment
and evaluation of signals that were likely to have a causal link with the associated medicine.
Active surveillance activities were found to be particularly limited among study countries
(table 19). Only the NRAs in Thailand reported conducting active medicine safety surveillance
in the last five years. Academia, including higher education institutions and organizations,
in all countries reported conducting active surveillance activities with the exception of
Cambodia. The University of Science and Technology in Bangladesh reported conducting
active surveillance studies for an anti-epileptic medication, diabetic medication, and oncology
medication. Industry and health facilities also reported conducting active surveillance activities
in Bangladesh, Philippines, and Thailand.
Bangladesh, Cambodia, and Thailand reported conduct of product quality surveys and
inspections by the NRA. None of the countries conducted studies in 2011 to quantify
medication errors.
r i s k a s s e s s m e n t a n d e va luat i o n 55
Table 19. Risk Assessment and Evaluation at the National Level
Spontaneous reporting
≥ expected ü
ICSRs with causality
assessed (≥50%) ü ü
Product quality survey
and inspections ü ü Yes ü
planned and conducted
Medication errors
studied ü ü
Medicine utilization
studies ü ü ü ü
Active surveillance
activities ü ü
Discussion
Medicine safety risks are typically identified within a country through signal generation
activities, which require further investigation to protect patients and safeguard public
health. The periodic review of suspected ADRs reported through passive surveillance and
evaluation of potentially important safety signals detected through active surveillance are
fundamental to any comprehensive PV and medicine safety system. A spontaneous report of
a suspected ADR generates a qualitative safety signal that may warrant further investigation
if the data is sufficiently complete and a causal relationship with a medical product is likely.
In contrast, active surveillance generates quantitative information that provides information
on the incidence (frequency) of safety events observed though various methods, including
cohort event monitoring, product exposure registry, sentinel-site cohort studies, large simple
trials, and other types of epidemiological studies (case-control study, cross-sectional study)
(European Medicines Agency 2005; Meyboom et al. 1997). Active surveillance is particularly
valuable for PHPs, such as HIV and AIDS, TB, immunization, and malaria control programs,
and can provide useful information for making evidence-based decisions involving the
selection of new medicines or revision of standard treatment guidelines. Study countries
represent a range of capacity related to the assessment and evaluation of medical products
safety signals. Risk assessment is essential in PV for it can provide the critical information
needed for prompt decision making. Countries need to increase their capacities for causality
assessment. Surveys on the quality of circulating medicines and related products as well as
studies on medication errors are also informative PV interventions.
The five countries have their PV system as a distinct unit that does not have much interaction
with the other units, particularly those involved in post-marketing surveillance for product
quality, inspection, and enforcement. For example, the quality control laboratory relationship
with the PV unit is weak and therefore opportunities for using the adverse events reporting
form for product quality and medication error surveillance is not being exploited. Product
quality surveillance generally occurs when the inspectors are out in the field to collect
samples for testing. Control of advertising and promotion is also handled separately and
complaints form for bogus promotional activities are nonexistent. Data collected from
serious and unexpected adverse reactions during clinical trials of investigational drugs
are not shared with the PV unit. Also, data from phase IV studies that have safety and
effectiveness as outcome of interest is not in the national PV databases
Risk Management
and Communication
Medicine Safety Information Requests Received and Addressed

in the Last Year
The assessment found that Thailand and Philippines have medicine information processes
that are in place and functioning with a minimum of one information request received and
responded to per month. Medicine information offices are also in place in Nepal and recently
established in Cambodia, although information requests are not yet routinely received or
addressed.
The assessment found that Nepal and Thailand regularly publish medicines safety bulletins.
However, the countries appear to still face challenges in the dissemination of medicine safety
information, including bulletins, to PV stakeholders. In Thailand, 10 of 12 (83%) health
facilities sampled reported receipt of the national medicines safety bulletin in 2011, but only
14 of 62 (23%) community pharmacies received the bulletin. In Nepal, 3 of 17 (18%) health
facilities and 1 of 15 pharmacies (7%) sampled reported receipt of the national medicine safety
bulletin in 2011.
All countries reported use of prequalification schemes, such as the WHO Prequalification
Programme, for procurement decisions related to at least some medical products, most
notably the national vaccine program. In the Philippines, for example, the government
considers WHO Prequalification in vaccine procurement decisions, though conducts its own
local prequalification practices for procurement of other medical products, such as generic
medicines.
Nepal, the Philippines, and Thailand estimated the levels of unregistered medicines in their
respective markets to be less than 1%. The assessment also found that Cambodia, which
closely monitors the quality of its medicines in part to proactively combat the emergence
of drug resistance, estimates the levels of unregistered medicines at 30%. Bangladesh
also estimates high levels of unregistered medicines within its market (Business Monitor
International 2013) and, as a result, its government has been vocal and proactive in
recognizing the need to address this threat to medicines quality and public health.
All countries studied reported that medical products were both sampled and analyzed for
quality in national medicines laboratories in 2011 (table 20).
NRAs in Cambodia, Philippines, and Thailand reported risk mitigation plans for high-risk
medicines. The assessment found that of the 5 countries sampled, 10 of 19 (53%) national
public health programs, 14 of 62 (23%) pharmacies, 17 of 86 (20%) health facilities, 8 of 38
(21%) pharmaceutical manufacturers, 0 of 7 medical device manufacturers, and 3 of 5 (60%)
clinical research organizations have risk mitigation plans for high-risk products in place
within their facilities. However, follow-up review indicated that countries have not adopted
risk-based approaches as standard practice. Formal risk-based regulation is an efficient way
r i s k ma n ag e m e n t aanndd co
commmmuunni c
i cat i onn
ati o 57
Table 20. Number of Medical Products Sampled and Analyzed for Quality
Medicines sampled that were analyzed for product quality
Country No. sampled No. analyzed % % failure
Bangladesh 3,720 2,687 69 0.04
Cambodia 1,837 1,837 100 4.6
Nepal 80 67 83 27
Philippines 4,298 4,185 97
Thailand 2,000 2,000 100 10
Blank denotes no data
to focus limited resources on high-risk products and reduce regulatory burden on low-risk
medicines. None of the countries have international risk management standards similar to
the ISO 31000:2009 (ISO).
The Philippines and Thailand reported identification of medicine safety issues from outside
sources such as other regulatory authorities including the US FDA, the EMA, and WHO. All
countries reported taking at least one medicine safety action other than ADR reporting, such
as issuance of safety alerts, recall of products, or withdraw of licenses within the last year.
National PV centers reported that at the health facilities level, medicine safety action may be
initiated by Drug and Therapeutic Committees (DTCs). All countries, with the exception of
Bangladesh, were found to have at least one DTC in place that took medicine safety action to
protect patient safety in 2011.
The assessment found some evidence of rapid communication methods for dissemination of
medicine safety information, including posting of medicines safety alerts on NRA websites in
Nepal, the Philippines, and Thailand. In Cambodia, the PV unit has an organized reporting
system whereby PV focal point persons in each provincial health department and operational
department are notified immediately by e-mail. Safety signals are then transmitted to health
workers and the public by phone, fax, and official MoH correspondence. Encouragingly,
Cambodia, the Philippines and Thailand reported alerting healthcare workers and the public
of medicine safety alerts within three weeks of the detection. Through a literature review
we identified that opportunities for regional information sharing on the safety and quality
of products are available through the countries participation in the regional harmonization
initiatives (RHIs). The PMA system of the ASEAN member countries can be used to notify
the various regulatory agencies in a timely manner about defective or unsafe health products.
However, at the time of the study, none of the ASEAN member countries studied was actively
sharing information through the PMA system.
Table 21. Public Communication Activities

Public or community education activities related to medicine safety
Country carried out in the last year
Bangladesh None through NRA; training and communication through pharmacist association.
Cambodia None
Nepal Media spots in newspaper; publication of drug bulletin; training on Good
Dispensing Practice through Nepal Pharmacist association.
Philippines Publicly available trainings through Philippines FDA Academy; training and
communication through professional associations
Thailand Public meeting on GMP; BE/BA 3-5 times per year; training and communication
through professional associations
The PV centers in Nepal, Philippines, and Thailand reported conducting patient education
activities related to medicine safety monitoring in 2011. In those three countries, as well as
Bangladesh, professional associations were also involved in education activities, namely
training and communication (table 21).
The assessment found that all of the countries surveyed had taken regulatory actions of some
kind in addition to ADR reporting in 2011 (tables 22 and 23). The most common actions
taken were changes to the EML, medicine formulary, or STGs; and issuances of safety alerts
(or Dear Doctor letter/Dear Healthcare Professional letter). In only a few countries were
products recalled, product licenses withdrawn, or marketing authorizations suspended—
actions generally only taken in extreme cases. In comparison, Singapore Health Sciences
Authority in 2011 issued 229 label changes, 23 product safety alerts, 6 product recalls, and
29 Dear Healthcare Professional letters.
Table 22. Other Medicine Safety Regulatory Actions Taken Besides

ADR Reporting in 2011
NRA action taken Bangladesh Cambodia Nepal Philippines Thailand
Label or package insert
changes/boxed warning ü ü
Treatment guidelines,
medicine formulary, or ü ü ü ü
EML changes
MoH memo or circular
referencing safety data ü ü
Product recalls ü ü ü
Withdrawal of product
license ü ü ü
Suspension of
marketing authorization ü ü ü
Risk management
activities recommended ü
due to safety data
Dear Dr. Letters or
safety alerts issued ü ü
Blank cell denotes that no action was taken.
r i s k ma n ag e m e n t a n d co m m u n i c at i o n 59
Table 23. Risk Management and Communication
Medicine safety
information requests ü ü
addressed
Regularly published
medicines safety ü ü
bulletins
Prequalification
schemes used in ü ü ü ü ü
procurement decisions
Unregistered medicines
in pharmaceutical ü ü ü ü
market <3%
Medicines sampled and
analyzed for product ü ü ü
quality >95%
Risk mitigation plans for
high-risk medicines ü ü ü
Medicine safety issues
identified from external ü ü ü
sources and acted on
Time from ADR
signal generation to
communication to ü ü ü
healthcare workers and
public <3 weeks
Public or community
education activities ü ü ü ü ü
on PV
Medicine safety action
taken other than ADR ü ü ü ü ü
reporting
Drug and therapeutic
committees addressed ü ü ü ü
medicine safety issues
Blank denotes that the indicator is not achieved.
Product Quality
Surveillance
This section consolidates the findings and analysis of the situation with monitoring the
quality of products at the national level. There are opportunities for addressing product
quality at each stage of the pharmaceutical management cycle. At the procurement stage,
the use of prequalified suppliers, including medicines prequalified under the WHO
Prequalification of Medicines Programme, and mandatory product registration help to
prevent substandard and falsified products from entering the supply system. The study
found that all five of the countries used prequalification schemes in some capacity in
medicine procurement decisions. With respect to product registration, all of the countries
required product registration with three of the five reporting that unregistered products
represented less than 3% of the products in the pharmaceutical market. During distribution
and storage, product quality surveillance monitoring includes shipment inspections, facility
inspections and routine sampling and testing. Only 2 countries have good distribution
practices (GDP) guidelines, while 2 others say the GDP is in draft. The study found that
Bangladesh, Cambodia and Thailand reported both planning and conducting product
quality surveys and inspections.
Although active quality surveillance activities can effectively prevent many unsafe
medicines from making their way through the various levels of the supply chain to the
service delivery points and the patients themselves, a comprehensive quality assurance
system must also have mechanisms in place to detect problems at the point of use through
the voluntary reporting of healthcare workers, patients and consumers. A voluntary
reporting system, which represents the passive approach to product quality surveillance,
can empower health workers and consumers to report products of suspected poor quality
(Strengthening Pharmaceutical Systems (SPS) Program 2011). It is especially important
for countries to implement, and maximize the benefits of the passive approach to product
quality surveillance, particularly when their active quality surveillance activities are weak
or limited in scope. The study found that only two of the countries—the Philippines and
Thailand—have a standardized product quality reporting form, which health workers
and consumers can use to report directly to the national PV program. Although some
health facilities surveyed in all of the countries responded that they have a product quality
reporting form for health workers, it was not confirmed if those reports were submitted
to the national PV program or remained within the facility. Product quality reporting
forms from pharmaceutical companies, which presumably are submitted directly to the
companies rather than to the national PV program, are reportedly more common in
the five countries. Although the results of the study suggest product quality reporting to
the national PV programs in the five countries needs to be improved across all groups,
consumer reporting appears to be the weakest. Reports of outbreaks of serious adverse
events, which are suspected of being related to product quality, will typically require an
investigation of causality and attribution of the adverse events to the suspected product.
These investigations include product quality analysis by national medicines quality control
p r o d u c t q ua l i t y ssuurrvveei li lllaannccee 61
laboratories and other qualified laboratories—at times working in collaboration with
technical partners, such as the USP/PQM program—that have the capacity to conduct the
necessary tests. All five of the countries in the study have a national quality control laboratory
or unit for product quality testing; however, only two of the countries’ labs had verifiable
capacity and performance: the Philippines and Thailand. The labs in those two countries
reportedly have quality management systems in place for QA/QC and have been audited
within the past five years. They also reported analyzing more than 95% of the samples they
received, as did Cambodia’s national lab. The labs in Bangladesh and Nepal analyzed 69% and
83% of samples, respectively.
After a quality problem is confirmed by a qualified laboratory, safety concerns related to

the product quality still need to be evaluated using epidemiological studies to confirm
attribution, quantify incidence and establish possible risk factors. Functional medicine safety
systems need to have the capacity and resources to conduct, or outsource, both laboratory
and epidemiological investigations in order to fully understand signals generated from
adverse events so that the necessary alerts can be communicated and shared. In developing
countries, where the national PV systems and regulatory authorities may not be adequately
staffed and resources are limited, academic or research institutions in the country with
the relevant skills and expertise may be enlisted to conduct the epidemiological studies.
In developing countries a majority of ADRs are in fact related to product quality issue.
It is important that coordination between PV centers and QC labs should be strong and
both should share information. In reality in countries with good PV systems, it’s often the
PV center who should that communicates information to QC lab which is responsible for
analyzing the quality of products. The QC labs usually receive medicines from different
sources; usually – Pre-market authorization, post-market surveillance, routine inspections,
and complains. Many health programs such also run quality monitoring programs (e.g.,
those receiving support from donors like USAID, or under obligation from the Global
Fund), so in reality quality monitoring is not only limited to post-market surveillance, so
the reporting mechanism between PV center and QC lab should be going both ways. This
is also to say that without having quality control capacity in developing countries, most AEs
will not be assessed effectively because a big majority of AEs are linked to product quality.
PV should be considered as part of quality assurance pillars in developing countries. Select
indicators related to product quality assurance in the five countries assessed are provided in
the table below.
Discussion
Regulatory authorities are expected to receive and respond to medicine information
requests from the PV stakeholders in their country. Half of the countries assessed had
functioning drug information systems. NRAs should be equipped and staffed accordingly
to provide medicine information to the public. It is also important for the NRA to publicize
the availability of medicine information service to ensure its optimal use by the public. A
key tool for medicine safety communication is the regular publication and distribution of
medicine safety alerts and newsletters, particularly medicine safety information and alerts of
local relevance. The alerts may be detected within the country through safety surveillance,
published in the WHO Pharmaceuticals Newsletter or released by regional regulatory
authorities and stringent regulatory authorities, such as the EMA and US FDA. Newsletters
should be regularly published in print as well as electronically and distributed via the NRA
or PV Center’s website; electronic methods, such as e-mail list serves; and, more traditional
methods, such as mailings. The assessment findings suggest that current efforts to publish
Table 24. Summary of Indicators related to Product Quality Assurance
Legal provisions
for product quality ü ü ü ü ü
assurance
Prequalification
schemes used in
medicine procurement ü ü ü ü ü
decisions
Unregistered medicines
in pharmaceutical ü ü ü
market < 3%
Product quality
Existence of a quality
control laboratory
(or unit) with clear ü ü ü ü ü
mandate, structure and
functions
Quality Control
Advisory Committee ü ü
Quality management
system for QA/QC ü ü
Guidelines for Good
Distribution Practices ü ü Drafting Drafting
in place
Product quality survey
and inspections ü ü ü
planned and conducted
Medicines sampled and
analyzed for product ü ü ü
quality (>95%)
Medicine safety issues
identified from external ü ü
sources and acted on
Blank cell denotes that no action was taken.
and disseminate the national medicines safety bulletins are reaching some stakeholders
within the PV system but not all, representing missed opportunities to communicate
medicine safety information to the point of care, particularly within community pharmacies.
Countries should safeguard their market by ensuring that unregistered medicines are not in
circulation and that registered medicines in the country’s supply chain are analyzed and are
of good quality. Measuring the volume of products analyzed together with the percentage
of analyzed samples that failed quality standards can indicate the extent of product quality
problems among the medicines circulating in the country. When tracked longitudinally,
countries can determine whether the problem has increased or decreased over time. National
medicines laboratories should not only test medicines submitted for analysis but also actively
sample medicines from the market for testing.
Medicine safety events can be either minimized or prevented when clear plans exist for
avoiding serious known risks of medicines, at both the NRA and health facility level. Some
medicines are considered high risk because they are known to cause significant adverse
events when prescribed incorrectly or used in error (Institute for Safe Medication Practices).
p r o d u c t q ua l i t y s u r v e i l l a n c e 63
Risk mitigation plans are used to prevent and manage ADRs by averting serious known
risks of medicines. Such plans allow for targeted, resource-efficient approaches to managing
known risks associated with medicines in which therapeutic benefit outweighs known risks,
such as certain oncology medications. Using limited PV resources for high-risk medicines
can improve the ability of the countries to efficiently safeguard public health.
Tracking external safety alerts from stringent PV systems such as US FDA and EMA is a cost-
effective approach to reach life-saving regulatory decisions. Equally important is the rapid
communication of relevant safety information to stakeholders from the national PV centers,
which should be established as an authoritative source of information. Medicine safety
information is only effective in safeguarding the public’s health if appropriate regulatory
actions are taken in response to safety threats. Regulatory actions, other than ADR reporting,
may include label or package insert changes; revisions to the EML, medicine formulary, or
standard treatment guidelines; circulation of MOH memos referencing safety data; product
recalls; withdrawals of product licenses; suspension of marketing authorizations; adoption of
risk management activities; and, dissemination of safety alerts.
Case Study 3.
Cambodia’s Success in Containing Unregistered Medicines
Controlling the sale of unregistered drugs on the market is a challenge for all countries,
particularly those operating in resource-constrained settings. In Cambodia, the Department
of Drugs and Food reports having capacity to identify the number of unregistered medicine
in retail outlets, pharmacies and drug stores. Faced with the emergence of resistance to drugs
such as antimalarials, the country has been proactive in closely monitoring the quality of
medicines. Thanks to these efforts, the proportion of unregistered drugs has fallen sharply from
30%* to 3%.**
* Pharmaceutical Sector Strategic Plan 2005-2015, DDF, Ministry of Health, 2005)
** MoH, DDF 2012
PV Capacity at
the National Level
Figure 3 represents the current situation and capacity of the PV systems at the national level
by countries as demonstrated by the assessment findings, which measured the degree to
which the countries had the key elements of a comprehensive PV system within each of the
five main components. Stronger capacity is depicted by distance further from the center of
the diagram, on a scale of 0 to 100%. As illustrated in the chart, Thailand has the greatest
capacity, achieving 100% in three of the five PV components and over three-quarters in
the other two. The Philippines also demonstrates strong capacity in four of the five areas;
however, its capacity in risk assessment and evaluation is negligible, pointing to a suggested
priority for their future efforts to strengthen the overall system. Although Bangladesh
scores low in four of the five PV components, the strength of its capacity in policy, law,
regulation, and governance provides a foundation and starting point for building up the other
components of its PV system.
Figure 3. National PV Systems Capacity in Five Asian Countries
National PV System Policy, Law, Regulation,

and Governance
100%
80%
60%
Systems, Structures,
Risk Management 40%
and Stakeholder
and Communication
20% Coordination
0%
Risk Assessment Signal Generation

and Evaluation and Data Mangament
p v c a pac i t y at t h e n at i o n a l l e v e l 65
Options for Strengthening
Pharmacovigilance at the
National Level
Based on the findings from the individual country assessments and the review of the PV
systems in the Asia region, we have provided options to be considered for addressing
the limitations across the studied countries and in the region. In determining the most
appropriate options, the level of development of the regulatory and PV system in the country
should be considered.
Strengthening Regulatory Policies and Framework

Regulatory policy should articulate government’s vision, principles, and practices for
ensuring quality and safety of products. It should include governance clauses to ensure
improved transparency of the functioning of the advisory committees, the participation
of civil societies, protection for adverse event reporters, performance metrics for the
regulatory authority to be held accountable, and evaluation of the impact of regulations. The
regulatory frameworks of the countries studied were not explicitly stated by the NRAs. The
Philippines has a National Policy and Program on Pharmacovigilance, which is a place to
start but an overarching pharmaceutical regulatory policy may still be needed. With regards
to the legislation, some aspects of the regulatory requirements for pre- and post-marketing
surveillance activities are either very dated or nonexistent. These findings are consistent with
the view expressed by a recent IOM report that some resource-constrained countries have
no laws governing product safety; others have laws that are confusing and contradictory
(Institute of Medicine 2012).
The studied countries have the following options based on the level of development of their
regulatory and PV systems for strengthening their regulatory policy and framework—
§§ Develop new pharmaceutical regulatory policies and frameworks to ensure that

regulations are effective and in the public interest or revise and consolidate the existing
ones.
§§ Streamline sections of existing legislation that deal with aspects of medicines quality,
safety, and post-marketing surveillance. Ensure that legislations are congruent with
other relevant local laws or embark on regulatory reform and the development of
entirely new legislations that will address emerging challenges for ensuring safety of
health products.
Ensuring Convergent Regional and International Regulations

PV regulatory requirements among the countries vary a great deal. For instance, countries
do not consistently require industry reporting of serious adverse events and the timelines for
reporting these varies. Requirements for the submission of periodic safety update reports are
o p t i o n s f o r s t r e n g t h e n i n g p h a r maco v i g i l a n c e at t h e n at i o n a l l e v e l 67
also varied. PV regulations that are not similar with those of stringent regulatory authorities
(SRAs) or other competent regulatory authorities and are too demanding to meet can be
an impediment to access to medicines. Conversely regulations that are too lax can expose
patients to harm (Lebega O, Nwokike J 2012).
Options for countries for developing regulations convergent within the Asian region—
§§ Map differences and provide guidance on regulations that the country considers as
equivalent to regional and international standards or develop guidance to industry to
explicitly document regional equivalencies.
§§ Alternatively, countries can completely revise their PV legislation to make them

convergent with that of stringent regulatory authorities and also consistent with
the regional harmonization guidelines within the Asia Pacific region and other
international guidelines. Some requirements countries could consider for convergence
with SRA requirements and consistency within the region include timelines for
reporting serious adverse events, PSURs, safety reporting during clinical trials , medical
device vigilance regulations, use of the common technical document for registration
application, requirements for PV plans and risk management plans, requirement
for industry to conduct post-authorization studies, PV inspections and audits, and
methods for benefit and risk assessments.
Improving Information Sharing and Participation in Regional

Harmonization Initiatives
The globalization of pharmaceutical production and distribution activities and the
increasing complexities of the products make the need for collaboration among regulatory
authorities critical. When individual regulatory authorities repeatedly inspect manufacturers
already inspected by others and fail to learn from the experiences of other regulators,
there is duplication and lost resources. Mutual recognition, criteria-based prescreening
or prequalification, and confidentiality agreements for regulatory information sharing are
efficient strategies to avoid duplicative activities. These strategies are part of the objectives
of regional harmonization initiatives. The ASEAN pharmaceutical product working
group allows participants to coordinate their regulatory requirements and information
sharing on the safety and quality of pharmaceutical products. However, countries seem to
only participate in these initiatives including the mutual recognition agreement on GMP
inspections and PMA system on a limited basis. The PMA presents an excellent opportunity
for collaboration to safeguard the supply chain in the member countries. When safety
concern that results in a recall or withdrawal happens, the system is used to notify the various
regulatory agencies through the focal persons appointed by each country.
Options for improving participation in regional harmonization initiatives—
§§ The ASEAN pharmaceutical product working group should consider strengthening

the PMA for collaboration and information sharing about product security in the
supply chain by ensuring active participation and/or expand the program to cover the
entire Southeast Asia region. The PMA should review its current functions, identifying
opportunities for improvement and the participation of member countries. The
review will help in setting up procedures and protocols. To improve its system, the
ASEAN working group can review the functioning of the pharmaceutical Inspection
Co-Operation Scheme Procedure for Handling Rapid Alerts and Recalls Arising
from Quality Defects (PIC/S 2011) the WHO drug safety alert system, and the United
Kingdom MHRA defective medicines alert system (Medicines and Healthcare Products
Regulatory Agency).
§§ The APEC AHWP should consider providing support to countries to begin the
development of their regulatory pathway for medical devices and/or actively support
countries efforts at capacity development for medical devices regulation.
§§ Since the SAARC and its standards organization South Asian Regional Standards
Organization currently do not have any initiative with regards to harmonization of
requirements for pharmaceuticals, an option can be to develop such initiatives. Another
option would be for Bangladesh and Nepal to consider opportunities for information
sharing with other regional harmonization groups in the region including the ASEAN
working group and the APEC AHWP.
Reforming Organizational Structure to Achieve Integrated

Safety Surveillance
Regulatory efficiency can be gained by restructuring the current operations of the post-
marketing surveillance activities within the regulatory system. Countries should explore
opportunities to review the structure for post-marketing regulatory activities. Across all
the countries assessed, the current system is fragmented and opportunities for leveraging
expertise and resources are not exploited.
Options for countries may include—
§§ Create a single vigilance center that can facilitate the integration of adverse events
reporting for all health products. This has been implemented by Thailand through
its HPVC. Also the Singapore Health Sciences Authority in 2009 renamed the
Pharmacovigilance Branch as the Vigilance Branch. The Singapore authority said
that this was important because the Vigilance Branch has expanded scope of safety
monitoring of all health products since the same underlying principles of safety
monitoring and risk management/mitigation applied to drugs are also applied to the
other health products (Health Sciences Authority). This option, however, does not
guarantee that all units involved in post-marketing monitoring will collaborate.
§§ Consolidate post-marketing surveillance department that brings together PV, product

quality surveillance, routine inspections, and control of advert and promotion into a
single unit. This will ensure that the different regulatory units dealing with these issues
are placed under the same department.
§§ Enhance safety information sharing that may ensure that all regulatory units have
systems in place to share databases and regulatory intelligence. Whichever option is
preferred, restructuring should aim at developing an integrated surveillance system that
is efficient and that supports the consolidation of all information about the safety of a
product.
Ensuring Efficient Safety Surveillance and Reduction of

Regulatory Burden
Some of the assessed countries’ laws are redundant or too overreaching and the countries
do not have the capacity to enforce them. When regulations are not enforced, it weakens the
motivation for compliance. Countries can reduce regulatory burden and achieve efficiency
through risk-based and risk proportionate regulations by adapting international risk
management standards like the ISO 31000:2009. In an effort to reduce administrative burden,
the United Kingdom MHRA introduced a system of self-certification by the industry for low-
risk medicines license variations (National Audit Office 2008). The authority also has a risk-
based approach to PV inspections (Medicines and Healthcare Products Regulatory Authority
2013). The Australian Therapeutic Goods Administration introduced a risk based approach
for regulating over-the-counter medicines. Countries should also reform their systems to
consolidate reporting requirements on the industry. Fewer forms lead to a reduction in
administrative and regulatory burden.
Possible options for countries to ensure efficient safety surveillance include—
§§ Explore opportunities for incorporating regulatory impact analysis as part of their

regulatory system. This will ensure that the economic impact of new regulations and
the determination of the cost-benefit of regulatory requirements are made part of the
regulatory practice.
§§ Identify the most efficient ways to protect the population from unsafe products with
minimal regulatory burden and using the limited resources available.
§§ Develop systems to ensure that PV regulations and enforcement efforts are risk
proportionate or implement risk-based approaches using relevant criteria which may
include the country of manufacture, falsification profile, storage and stability of the
product, inspection history, and regulatory intelligence from other NRAs.
Improving Funding for PV

The assessment found that funding for PV is very limited. With limited budgets, regulatory
authorities should revisit how they use the existing resources to achieve their mission to
safeguard the public. Many countries have lopsided way of allocating their resources favoring
registration over enforcement and post-marketing surveillance activities. In the United States,
The US IOM committee on assessment of the US drug safety system found an imbalance in
the regulatory attention and resources available before and after approval. Staff and resources
devoted to pre-approval functions are substantially greater.4 Less than 10% of products many
regulatory authorities in LMICs register are new medicines that have never been registered
elsewhere and therefore require full reviews. If countries reduce the need for duplicative
reviews and inspections, they may have more resources for monitoring the safety and
effectiveness of the products and enforcing regulatory actions.
Typically this is seen in terms of lack of dedicated budget for PV or the lack of staff dedicated
to drug safety. Only Thailand confirmed that they have dedicated budgets available for PV
activities. However, the consensus is that there is the need to develop innovative and rational
means for funding regulatory and drug safety activities.
Options to countries for improving funding for PV include—
§§ Review resource allocation and use to determine the value for money for regulation and
determine an evidence-based approach to resource allocation to regulatory function.
§§ Consider improving allocation to PMS including in-country product quality

surveillance, licensing, in-country inspection, and enforcement activities.
4 Burke S. Chair, IOM Committee on the assessment of the US drug safety system. Statement before the committee on
Health, Education, Labor and Pensions, US Senate. Nov 16, 2006.
§§ Identify other sources of funding. Options that exist include full public funding of PV
or user fees charged to the industry, or some blending of these approaches. Germany
and France use the full public funding option for all their regulatory activities, France
case may be related to the benfluorex case of increased risk of heart valve diseases. In
the EU, the introduction of the new legislations Directive 2010/84/EU and Regulation
1235/2010 requires the EMA to charge user fees for its PV services. The proposed fees
include yearly service fee per product; fees for PSUR and post authorization safety
studies (PASS), and referrals assessments. From the third reauthorization of the US
Prescription Drug User Fee Act in 2002, the FDA is empowered to spend part of the
fee on drug safety activities. The act versions IV and V have expanded the FDA’s drug
safety responsibilities and also the resources allocated. Funding PV through user fees
charged on the industry is controversial because of concerns about potential conflicts of
interest (HAI Europe 2012).
§§ Use of percentage of sales turnover. This method has been used in drug relief funds in
Taiwan and Japan. To address the issue of additional funding for PV activities, a first
step could be for governments in the studied countries to meet with stakeholders and
discuss options.
Developing Comprehensive PV Guidelines

Countries should revise their PV national guidelines to make them more encompassing and
address all issues related to safety and quality of medical products. Comprehensive national
PV guidelines should address therapeutic ineffectiveness, medication errors, medical device
vigilance, monitoring safety of blood products, control of promotional activities, and other
emerging issues. The guidelines should also provide for the use of other epidemiological
methods including active surveillance and large simple studies to complement passive
surveillance. The national guidelines discuss the role of civil societies, conflict of interest,
declaration of assets, and confidential financial disclosure by safety advisory committee
members. The guidelines should also, prescribe procedures for meetings and contacts
between the NRA and the regulated industries, dissemination of NRA deliberations/freedom
of information, ombudsman, and existence of transparency measures and indicators.
Options for developing the guidelines may include—countries could revise existing
guidelines or develop government circulars to address areas not included in the current
guidelines. Alternatively, new comprehensive national PV guidelines could be developed
by engaging the participation of all stakeholders and ensuring adequate buy-in from the
regulated industry and government commitment to safeguard the safety of everyone exposed
to all health products.
Strengthening Spontaneous Reporting

The assessment found that countries have approved national ADR forms, but their
availability at the health facilities is limited. Only Thailand achieved the number of reports
recommended by WHO. Several strategies can be used to strengthen reporting to facilitates
signal generation and evaluation. Generated signals allow risk management to prevent
further harm from the product. With the increasing diffusion of modern information
technology it is clearly within reach to set up integrated health products surveillance system
that will help improve understanding of medicines’ safety and effectiveness during real-life
use and also monitor quality of products in the supply chain.
Possible options for strengthening spontaneous reporting include—
§§ Use of information technologies for improving reporting include the adoption of online
reporting forms, interactive PDF forms, reporting through electronic medical records,
and cell phone text messaging. Cell phones are widely deployed in the countries
studied, measured in terms of mobile cellular subscriptions per 100 inhabitants in
2010, except for Nepal (30.69). Philippines (85.7), and Thailand (100.8), have high cell
phone diffusion that can be a good tool for post-marketing safety surveillance activities.
Consumers can send reports of adverse events they think are related to medicines they
used or report products with suspicious quality. These reports can be sent through
prepaid lines. This type of system is currently being implemented in other countries
(mPedigree).
§§ Adopt international standards for reporting. Assessed countries have not fully adopted
ICH E2B format or the CIOMS I forms for the reporting of adverse events. The
international safety reporting standard used by the SRAs and WHO for ICSRs is the
ICH E2B standard.
§§ Explore opportunities to consolidate or streamline reporting forms for all health

products (drugs, biologics, vaccines, and medical devices) and for reporting on safety
and quality issues. The Thai FDA HPVC has a single form for reporting events related
to all health products. Countries should also strengthen their data management
capabilities to be able to consolidate or at least have easy access to pre- and post-
authorization safety data on key products. This will allow for the construction of a more
comprehensive safety profile for those medicines. Data from development safety update
reports, spontaneous reporting system, and PSURs should be made easily available for
review for taking regulatory decisions. A pre-registration clinical trial safety database
can be a useful reference for flagging safety concerns that should be prioritized for
post-marketing studies, thereby using the complementary roles of the pre-market and
post-market safety data (O’Neill 1998). The HPVC single form for all events is also used
for adverse events reporting in clinical trials.
§§ Develop online database for managing reports. The EMA has the EudraVigilance which
is a data processing network and management system for reporting and evaluating
suspected adverse reactions (EudraVigilance). The EU recently launched the European
database of suspected ADR reports. The database is in most of the EU languages and
provides immediate reports on reported suspected ADRs of medicines and several
other reports that can be viewed through an interactive online PDF.
§§ Develop regional PV centers. Adverse events reporting can be improved by designating

regional PV centers, particularly in university hospitals where there is access to
qualified physicians, pharmacists, and nurses. In South Korea, the adverse events
reporting pattern was dramatically improved with the expansion of the regional
PV centers (Kimura et al. 2011). Other options include raising public awareness of
medicines safety and adverse events reporting among professional and consumers
associations. This option can be beneficial in countries where the associations are
already engaged in PV activities like the Thailand Adverse Drug Reaction’s Community
of Pharmacy Practice.
§§ Countries should consider adapting the Thailand Safety Monitoring Program or

related programs to ensure the safety of new medicines introduced in their countries.
Although the SMP has not been evaluated since it was established in 1991; anecdotal
reports indicate that the program has helped to improve adverse events reporting
for new medicines and improved watchfulness for better understanding of the safety
profile of the new medicine. Similar schemes by other regulatory authorities include the
EMA black triangle, Japan Early Post-Marketing Phase Vigilance, and the China SFDA
requirement for a five-year monitoring period for new medicines. These programs are
specifically for new chemical entities or new routes and new indications for existing
medicines. Re-examination or re-evaluation after such intensive monitoring provides
opportunities to review the safety profile of the product again before allowing it to be
used more widely.
Confronting Falsified and Substandard Products

Both passive and active methods are required for confronting the public health challenges
of falsified and substandard medicines and health products. Passive method enables the
reporting of products of suspected poor quality through the use of adverse events form by
both health workers and consumers. The active approach to quality surveillance includes
pre- and post-marketing activities that are conducted during production, procurement,
distribution and storage of pharmaceutical products, before they reach the point of use. Pre-
marketing activities include chemistry, manufacturing and control (CMC) management and
GMP inspections of pharmaceutical manufacturers to identify potential quality problems
during the production phase. At the procurement stage, the use of prequalified suppliers,
including medicines prequalified under the WHO Prequalification of Medicines Programme,
and mandatory product registration help to prevent substandard and falsified products from
entering the supply system. Options for improving the monitoring of product quality include:
§§ National PV systems have traditionally focused on ADR reporting while product

quality monitoring programs have been implemented in parallel, with limited
coordination or integration of the two. This separation in the reporting and
management of adverse events and product quality issues represents a missed
opportunity, which limits the effectiveness and efficiency of a quality assurance
system. PV systems are an optimal platform for the implementation and management
of reporting of suspected product quality problems by health workers, patients and
consumers as part of countries’ overall quality assurance efforts. Many countries,
including the United States, use their adverse events reporting system for the reporting
of suspected product quality issues, including the use of the same form for both
reports. Consolidating reporting within PV systems in this respect can be beneficial to
developing countries, particularly to the extent that it makes the system more efficient
and contributes to increase reporting. For the PV system, the integration of the two
reporting mechanisms, including the use of a single standardized form, reduces the
number of forms that need to be designed, implemented and managed and facilitates
cross-referencing of report information related to the same product, but generated
through the two different types of reports. For health workers, patients and consumers,
a single form designated for their particular use and a single reporting procedure
facilitates the process for them and reduces confusion, which might otherwise
discourage them from reporting. It can also help with the leveraging of resources
for both investigation and enforcement on the part of the regulatory authority. In
the Philippines and Thailand which have product quality reporting forms for health
workers and consumers to report directly to the PV program, the forms are integrated
into, or are a subset of, the adverse events reporting form, as recommended here.
§§ Donors and SRAs should consolidate their support to expand the activities of the WHO
rapid alert system as a vehicle for addressing the issues of falsified and substandard
products. Cambodia and the Philippines are already participating in this program.
A recent IOM report recommends that consistent use of the rapid alert form and
eventually linking it to national PV systems would advance international discourse and
give a more nuanced understanding of the extent and type of falsified, substandard, and
unregistered medicines that circulate around the world (Institute of Medicine 2013).
§§ Donors and SRAs should provide support to NRAs of the studied countries to improve
their regulatory systems and enforcement capabilities for addressing false products. The
NRAs should also be supported to develop new legislations that can positively support
efforts in this direction including the requirement for traceability for pharmaceutical
products. The industry could be required to implement barcoding and other strategies
to track and trace products. Barcoding can also facilitate product recalls and improve
patient safety. A couple of LMICs regulatory authorities recently required barcoding
of pharmaceutical products. Countries should empower consumers to be watchful
vanguard for product quality. The assessment identified the key use of the reporting
platform of PV to support product quality reporting. As more consumers become more
familiar with these reporting tools, they should be empowered to be the watchdog for
fake products.
PV Results in
Public Health Programs
The assessment included interviews with representatives from 19 national HIV and AIDS,
malaria, TB, and immunization programs across five countries.

Among public health programs assessed, 16 of 19 (84%) reported having a policy document
for PV or medicine safety and a policy document for product quality assurance.
Systems, Structure, and Stakeholder Coordination

Among public health programs analyzed, 37% were found to have a PV group or unit
assigned responsibility for monitoring medicine safety within the program. And all but one of
those reported that the PV unit had an official document with clear mandate, organizational
structure, roles, responsibilities, and reporting lines. Two PHPs additionally reported having
at least one dedicated staff member responsible for PV or medicine safety activities, for a total
of 47%. Fifty three percent reported existence of a unit that provides query response service
on ADRs and medicine safety information.
Funding for PV-related activities was found to be limited among PHPs within the five
countries studied, with only 26% found to have dedicated funds available. Several PHPs
reported having SOPs (53%) and guidelines (58%) in place that addressed elements of PV.
In Cambodia and Thailand, where a national PV guideline exists, the assessment found that
only 43% of PHPs reported having knowledge of their national PV guidelines. Two PHPs
in Cambodia and one PHP in Nepal (16%) reported having a safety advisory committee or
unit that is responsible for monitoring and discussing medicine safety related issues within
the program that met at least once in 2011, has clear guidelines for decision making, and a
guideline on conflict of interested related to decision making. Nearly all of the PHPs sampled
were reported having basic communication technologies available to improve access to
safety reporting and provide medicine information (84%) and a third have core medicine
safety reference materials available and in use (63%). In all countries, healthcare providers
such as physicians, pharmacists, and nurses within PHPs were trained on PV and medicine
safety in 2011, for a total of 58%. Most (79%) were familiar with the national PV center as the
coordinating body for PV within the countries studied and saw a role for their program in
ensuring medicine safety within their program (table 25).

Less than half of the PHPs studied (42%) reported keeping a log or database of PV data
collected and transmitting data to the national PV center. In some cases, PHPs were found
to be conducting signal generation activities, yet failing to submit the ADR reports to the
national PV center for analysis and regulatory decision making. Of the PHPs assessed, 58%
had a national ADR form on hand within their program at the time of the assessment. Very
p v r e s u lt s i n ppuubblli c lthh pprrooggrraammss

i c hheeaalt 75
Table 25. Results of System, Structure, and Stakeholder Coordination in
Public Health Programs
Indicator Responses (%)
PV unit in place 7/19 (37%)
At least one staff member responsible for PV activities 9/19 (47%)
Unit that provides query response service on ADRs 10/19 (53%)
Funding available 5/18 (26%)
SOPs that address elements of PV 10/19 (53%)
Guidelines that address elements of PV 11/19 (58%)
Basic communication technologies available 16/19 (84%)
Medicine safety reference materials available 12/19 (63%)
Healthcare providers trained on PV activities 11/19 (58%)
Healthcare providers familiar with national PV center 15/19 (79%)
few (29%) collected information on product quality, medication errors (0%), or treatment
failure (21%), in large part because of the lack of ADR national collection forms (table 26).

None of the PHPs studied were found to collect spontaneous ADR reports at expected
levels—100 reports per million of the PHP’s patient population—and also report those ADRs
to the national PV center. The national immunization program in Bangladesh reported
collecting 1,100 adverse events following immunization reports in 2011 against a patient
population of 3.7 million children vaccinated, for example, though none of the reports were
transmitted to the national PV unit. Two PHPs in Thailand documented adverse events
within more than 1% of their patient population or more in 2011.
Risk assessment and evaluation activities in the PHPs studied were minimal. In 2011,
three conducted product quality surveys, one conducted a medication error survey, and
four conducted medicine utilization surveys. Half of the PHPs (8 of 16) reported active
surveillance activities, though some activities were potentially targeted to disease instead of
medicines safety surveillance.

Very few PHPs reported receiving at least one request per month for medicine safety
information in 2011 (11%). In Thailand and Nepal, where the PV centers regularly publishes
a medicine safety newsletter, only three of eight PHPs received the bulletin. Nearly all PHPs
(89%) reported considering prequalification schemes such as the WHO prequalification or
the Pharmaceutical Inspection Cooperative Scheme when making medicines procurement
decisions, frequently linked to the procurement of products through donor mechanisms
requiring such controls. Only about one-third of PHPs studied submit medicines for quality
testing. In some countries, including Nepal, standard QC testing was not conducted prior
to products’ distribution in country when products were provided by reputable donors
including the Global Fund because of an assumption that the quality of such products are
already assured and medicine safety surveillance is therefore not necessary or beneficial
to the program. Risk management plans are currently in place that is targeted at high-risk
medicines in (53%) programs (table 27).
Table 26. Results of Signal Generation and Data Management in Public
Health Programs
Database of PV data 8/19 (42%)
National ADR form 11/19 (58%)
Collect information on product quality 4/14 (29%)
Collect information on medication error 0/14 (0%)
Collect information on treatment failure 3/14 (21%)
Table 27. Results of Risk Management and Communication in Public Health

Programs
Received at least one request per month for medicine safety 2/19 (11%)
information
Reported consideration of prequalification schemes when making 17/19 (89%)
medicines procurement decisions
Submit medicines for quality testing 1/3 (33%)
Risk management plans in place 10/19 (53%)
Limitations were found among PHPs related to managing medicine safety information. Only
one PHP reported identifying medicine safety issues of local relevance from outside sources
such as the WHO, EMA, FDA, or other relevant Asian sources in 2011. Better communication
channels were found to be in place between PHPs and healthcare workers and the public.
More than half of the PHPs studied (10 of 19 [53%]) reported less than three weeks between
identification of a significant safety issue such as a serious adverse event and communication
to healthcare workers and the public. Eleven conducted training related to medicine safety
or PV in 2011. Medicine safety action other than ADR reporting was found to be limited
within PHPs because of their role outside of national regulatory systems. However, almost
half reported taking some action such as distributing medicine safety alerts received from the
national PV center.
PV Capacity at the PHP Level

As evidenced by Figure 4, Nepal has the weakest PV system at the PHP level, while
Bangladesh and the Philippines have the strongest. Almost all of the countries achieved 80-
100% fulfillment in policy, law, and regulation.
Discussion
Policy documents that address the recognition of the need for the monitoring of the
safety and quality of products are essential in the public health programs that deal with
the entire population of a country. The results indicate that PHPs have challenges in
establishing funding and structures for PV within their programs. These challenges limit
the opportunities for using PV to inform treatment guidelines changes and for improving
treatment outcomes. The PHP programs in most countries are equipped to collect clinical
level data on patients. At the program level, the majority also routinely collects indicators for
monitoring programs’ performance. However, adverse events reporting are weak at the PHP.
p v r e s u lt s i n p u b l i c h e a lt h p r o g r a m s 77
Figure 4. National Public Health Program
National Public Health Policy, Law, Regulation,

Program and Governance
100%
80%
60%
Risk Management 40%
and Stakeholder
and Communication
20% Coordination
0%

Collecting data on real-life safety and effectiveness of medicines used on those programs and
using the information will contribute to improving treatment outcomes. Doctor’s notes on
every patient on PHP whose treatment was switched most times indicate why the treatment
was changed either the product was ineffective or patients could not tolerate the product.
Both events are reportable adverse events. The reporting of medication errors is almost
non-existent in the PHPs. Medication errors, for instance, the use of medicines when they
are contraindicated, contributes to poor outcomes in HIV and AIDS programs. Substitution
due to ARV toxicity can account for as much as 45.5% of treatment modification (Boulle
et al. 2007). PV is particularly important for antiretroviral therapy programs because some
patients will remain on antiretrovirals for their whole life, some of the long-term toxicity of
the products has not been completely defined, and the effectiveness of treatment program can
be compromised by problems related to toxicity. Monitoring long-term toxicity is therefore
necessary and of value to the treatment programs (Bisson et al. 2003).
Public confidence on the efficacy of ARVs was part of the reasons why most patients
agreed to seek care; safety concerns can negatively impact treatment continuation. Loss
of confidence in the safety of ARVs could lead to poor adherence and the emergence
of drug resistance, reduced demand for therapy, or inappropriate switching to more
toxic or expensive medicines. All the countries studied are currently implementing
public health programs (including vaccine programs, HIV and AIDS, TB, and malaria).
Pharmacogenomics can be useful in understanding ARV-related hypersensitivity reactions
that are human leukocyte antigen-associated. The work of the Thailand Pharmacogenomics
Network and others can contribute in that direction. The cost for setting up and running
safety studies can be prohibitive for developing countries, and many developing countries
lack the systems to systematically review and translate the findings into practice. Conversely,
routine surveillance can be less-prohibitive and the findings have more opportunities to be
fed into quality improvement practices. LMICs could benefit more from leveraging existing
surveillance systems for safety monitoring than relying only on ad hoc studies.
Options for Strengthening PV Systems at the PHP Level
Strengthening Routine Collection of information on the Tolerability
of Medicines
Countries PHPs have several options they can adopt to improve adverse events data
collection. They can encourage routine documentation of the reasons for treatment switches
in the patient’s case file, which can later be transcribed and processed as a report. Countries
can also develop a system to transcribe patient records periodically and study the frequency
of switches and tolerability of the medicines use. Data obtained should be shared with the
PV center.
Improve PV Funding for within the Program

PHPS do not necessarily need to establish their own PV center, but they will benefit from
identifying a staff responsible for PV who can collaborate with the national PV center. Having
in place a medication safety or quality assurance staff member and providing specific funding
for PV activities will improve patient safety within the program. Alternatively, PHPs also have
the option to fund the national PV center with dedicated funds to study priority safety issues
of interest to the program.
Develop Sustainable Risk Assessment and Evaluation Activities

In many of the countries studied, the PHPs have existing data collection systems for disease
surveillance activities. Though typically fragmented, they have cohorts that can be used to
study adverse events; therefore product safety surveillance can piggy-back on these systems.
Countries should exploit these opportunities and develop an integrated safety surveillance
system to support their public health programs. Countries should define their priorities
in the areas of risk evaluation. The first step will be to have a formal process to determine
research priorities on safety and quality of health products and identifying the need for post-
authorization safety and effectiveness studies. Countries should explore opportunities for
establishing sentinel sites for active surveillance, such as working with ART or TB programs
to set up cohort event monitoring and then develop steps on how to use the information from
safety studies to make decisions. Alternatively, PHPs can collaborate with their regulatory
authorities, stringent regulatory authorities, and donors to form surveillance networks.
There is a need for more collaboration and networking that can reuse existing infrastructure
to conduct longitudinal studies. Such networks will enable countries to participate in
cohort event monitoring collaborations. Observational cohorts based at health facilities are
potentially valuable sources of information regarding medicine use, treatment effectiveness,
adverse events, treatment discontinuations, program-based/systems-based treatment
availability (or alternatively, stock-outs), and drug resistance (Miller, Nwokike, and Stergachis
2012) An example of a HIV cohort collaboration that includes safety surveillance is the US
National Institutes of Health-sponsored International Epidemiologic Database to Evaluate
HIV/AIDS cohort network. Also the Antiretroviral Pregnancy Exposure Registry, an ongoing
surveillance on pregnancy outcomes for women receiving ARV medicines is another example
of a collaboration of many stakeholders. The EMA developed the European Network of
Centres for Pharmacoepidemiology and Pharmacovigilance to strengthen post-authorization
monitoring of medicinal products in Europe. These experiences can be reviewed to guide
donor and SRAs in supporting the countries to set up similar cohort collaboration for the
surveillance of safety of key products.
p v r e s u lt s i n p u b l i c h e a lt h p r o g r a m s 79
Include PV in Donation Programs
Donors and technical institutions that support providing medicines and health technologies
should require their programs to conduct spontaneous reporting, active surveillance, and
risk management, particularly for newer medicines, vaccines, and medical devices. Many
countries receiving donated products for their public health programs from donors have
limited capacity for post-marketing surveillance. The support from donors in making
these medicines available has saved lives. Some of the donations from the global health
initiatives such as PEPFAR and Global Fund have provided a life-line for the transforming
the health system of those countries. After the initial focus on emergency provision of health
interventions to those most in need, some of these global health initiatives are now focusing
on the need for health systems strengthening. PEPFAR should do more to support PV
systems in countries. This will become important as data for treatment guidelines revisions
are increasingly needed and as patients remain longer on treatment, highlighting the need
for data on long-term toxicity of the products. The launch of new medicines may provide
opportunity and new challenges for PV as shown by the recent registration of bedaquiline
by the USFDA with post-marketing surveillance conditions. The Global Fund has also
recognized the need for supporting PV. A recent panel that reviewed the fiduciary controls
and oversight mechanisms of the Global Fund recommended that the principal recipients
be required to systematically invest more of grant budgets in PV programs that monitor the
quality, usage, and efficacy of the drugs it buys, and that can track adverse events among
patients and other post-marketing product defects.
PV Results at
the Service Delivery Level
The assessment surveyed a total of 86 health facilities in the five countries. We defined health
facilities as clinics and hospitals in both the public and private sector. A breakdown of the
number and types of health facilities (public versus private) is presented in the table 28 below.
Table 28. Number of Health Facilities Surveyed

Health facilities
Country Public Private Total
Bangladesh 14 9 23
Cambodia 6 5 11
Nepal 9 8 17
Philippines 15 8 23
Thailand 9 3 12
Total 53 33 86
In addition, 62 private or community pharmacies in the five countries were surveyed for
the assessment. Community pharmacies in developing countries are often the first point
of contact for patients seeking medicines. Thus, although physicians (and industry where
mandated) have historically been the primary sources of adverse event reporting within
countries, pharmacy workers also play an important role within PV systems, given their
accessibility within communities and direct contact with consumers. Pharmacies also may
serve a critical role within comprehensive PV systems as one of the primary sources of
information for the general public regarding the use of medicines.

An awareness of the policies, laws and regulations related to the monitoring and reporting
of adverse events is important for private or community pharmacies to understand their role
and responsibilities in the PV system. The assessment found that nearly half (47%) of the
community pharmacies were aware of a national policy for monitoring and reporting adverse
events; just over a third (37%) were also aware of the law and regulations related to the same.
Systems, Structure, Stakeholder Coordination

The assessment findings indicate that the majority of health facilities do not have internal
systems and structures for PV that extend beyond those offered through the national system.
Less than half of the public and private health facilities surveyed in the five countries have
a PV center or unit, or designated staff for PV-related activities, within their facility (table
29). We defined a designated staff as someone who has PV-related functions in their job
description irrespective of their primary roles. Such staff may be the medication safety
p v r e s u lt s at tthhee sseerrvvi c ry lleevveell

i cee ddeelli vi veery 81
officer, quality assurance staff, pharmacists, nurse in charge of quality improvement, etc.
Even fewer health facilities have a dedicated budget available for PV-related activities. Fifteen
percent have a DTC at their facility. A quarter of the facilities reported having a copy of the
national PV guidelines that have been updated within the last five years, all of which were
in Thailand and the Philippines, while nearly a third reported having SOPs for PV-related
activities, including ADR reporting. Twenty percent of all of the countries indicated that
their healthcare workers had been trained on PV and medicine safety in the last year. For
the provision of medicine information, 38% of the facilities have a medicine information
or PV service that can address ADR and medicine safety-related questions and nearly half
reportedly have core reference materials on medicine safety available at their facility. Over
three-quarters have at least the minimum communication technologies to provide medicine
information and access to medicine safety reporting. Although the majority of health
facilities did not have strong systems and structures in place to manage medicine safety
reporting and information provision in a centralized manner, a few of the respondents in the
assessment noted that those matters were typically handled on the individual provider-level
and in the patient-provider interaction.
A quarter of the private or community pharmacies surveyed are aware that a national PV
center exists in their country (table 30). Nearly a third reported that they are aware of and
have used a service to ask questions related to ADRs and medicine safety information. Our
findings suggests that community pharmacies may also use services offered by sources
other than just the national PV center, such as pharmaceutical companies. Eighty percent of
pharmacies reported a role for pharmacies as PV stakeholders in ensuring medicine safety.
Ten percent (n = 6), all of which were in Thailand and the Philippines, reported awareness of
national guidelines for PV or PV policy equivalent.
Table 29. Results of Systems, Structure, and Stakeholder Coordination at

Service Delivery Level
Indicator Percentage
PV unit in place or designated staff for PV activities ~40%
Dedicated budget for PV-related activities 12%
DTC at facility 15%
National PV guidelines available and updated within last 5 years 25%
SOPs for PV related activities including ADRs ~33%
Healthcare providers trained on PV activities 20%
Medicine information or PV service that can address ADR-related questions 38%
Core reference materials on medicine safety at facility ~50%
Minimum communication technologies to provide medicine information >75%
and access to safety reporting
Table 30. Results of PV Related Activities Among Private Pharmacies Surveyed

Aware that national PV center exists in country 25%
Aware of and used a service to ask ADR related questions ~33%
Reported role for pharmacies as PV stakeholders in ensuring medicine safety 80%
Reported awareness of national guidelines for PV 10%
Although the ADR reporting form was the most commonly available PV-related form at the
health facility level, less than half of the health facilities surveyed in the five countries had an
ADR reporting form available at their health facility at the time of the assessment (table 31).
Approximately a quarter of facilities had a form for reporting medication errors, less than a fifth
had a product quality reporting form, and only 6% had a form for reporting treatment failures.
The forms available included those provided by the national PV system and forms provided
by individual public health programs and pharmaceutical companies. Adverse events may be
more commonly reported in patients’ files rather than recorded centrally or in the provided
forms, which allows for individual assessment and action, but does not allow for trend analysis
and risk assessment. A fifth of the health facilities surveyed had a consumer reporting form
available for patients (table 31). Consumer reporting of suspected ADRs and other related
medicine safety concerns seem to occur more often through personal communication between
patients and medical staff, which puts the onus on healthcare providers to report the event and
any other medicine-related problems through the formal forms and channels, where they exist.
Table 31. Results of Signal Generation and Data Management at

Health Facilities Level
ADR reporting form available at health facility 41%
Form for reporting medication errors ~25%
Product quality reporting form 18%
Form for reporting treatment failures 6%
Consumer reporting form 20%
In addition to generating safety signals, health facilities can collect relevant medicine safety
information not only from the ADR and other medicine-related reports submitted within
their facility but also from other in-country sources, including medicine safety bulletins and
alerts from regulatory authorities, PSURs, and additional published safety data generated
from clinical trials, active surveillance activities, medicine utilization surveys, and product
quality surveys. Medicine information centers within health facilities typically have the
responsibility to collect and distribute such information. A quarter of the health facilities
reported having an information system or database within their facility for collecting,
collating, and managing PV data and other relevant medicine information from their facility,
in-country sources, or international sources, such as WHO.
Given that pharmacies are a primary source of medicines and have direct contact with
patients, they have an important role to play in generating signals for the PV system.
The assessment found that 20% of private pharmacies have some kind of ADR reporting
form available, 20% have a product quality reporting form, and 20% have a medication
error reporting form (table 32). In many cases, the available data are from pharmaceutical
companies or suppliers, rather than from the national PV center or MoH. To engage
consumers in reporting suspected adverse events, product quality issues’ and medication
errors, reporting forms should be available at all service delivery points, including private
pharmacies. Only 6% of the pharmacies surveyed had a consumer reporting form available at
the time of the assessment. Substantial opportunity exists to improve the availability of these
forms at the pharmacy level.
p v r e s u lt s at t h e s e r v i c e d e l i v e ry l e v e l 83
Table 32. Summary of Results among Private Pharmacies Surveyed
ADR reporting form 20%
Product quality reporting form 20%
Medication error reporting form 20%
Consumer reporting form 6%

Less than a third (26%) of the health facilities surveyed in the five countries for this
assessment had received an adverse event form. However we could not determine how many
of these reports were submitted to the national PV program (or a pharmaceutical company)
in the last year. In Bangladesh and Nepal, none of the health facilities indicated that they
had reported a suspected ADR to the national level, although in some cases they may have
reported to a sub-national level, which would have then been responsible for reporting to the
national level. Twenty-two of 84 facilities (25%) had submitted 100 spontaneous reports per
million population served at their facility (or fraction thereof) in accordance with the WHO
recommendation. Those that met the WHO target were from Thailand and the Philippines.
Assessing risk requires information not only on ADRs but also on product quality,
medication errors, and medicine use. In 2011, the last full year preceding the assessment,
product quality surveys had been conducted at one-fifth of the health facilities, medication
error studies at one-quarter, and medicine utilization studies at one-fifth (table 33). The
health facilities that carried out these surveys and studies were mainly in Thailand and the
Philippines. The health facilities in Cambodia had not conducted any surveys or studies.
Approximately a quarter of the health facilities in the assessment in Thailand and the
Philippines reported active surveillance activities that are currently on-going or have been
carried out in the last five years.
All of the private pharmacies that reported collecting and submitting ADR reports were in
Thailand, with the exception of one in Nepal. Two of the Thailand pharmacies have met the
recommended threshold of spontaneous reports (i.e., more than 100 reports per million
population served—6,952 reports in 2011). No private pharmacies in Bangladesh, Cambodia,
or the Philippines reported collecting or submitting any ADR reports in the previous year
(2011).
Table 33. Results of Risk Assessment and Evaluation at Service Delivery Level
Product quality surveys 20%
Medication error studies 25%
Medicine utilization studies 20%
Active surveillance activities (e.g., cohort studies) ~25%
The assessment found that over 33% of the health facilities use prequalification schemes
in medicine procurement decision-making—in many cases because of the country’s
procurement policies, which mandate procurement of prequalified medicines when
possible—to prevent the occurrence of adverse events related to poor quality products.
Sixteen percent of the health facilities reported having sampled and analyzed > 95% of
medicines for product quality in the previous year by sending samples to quality laboratories.
Twenty percent have risk mitigation plans currently in place.
Twenty-four facilities (slightly above 25% to assessed facilities in study) in Nepal, Thailand,
and the Philippines reported that they had received medicines safety bulletins from their
national PV centers. Health facilities in all countries had received medicine bulletins of some
kind, if not from the national PV center, then from the MoH, NGOs, or pharmaceutical
companies. Whether the ADR signal generation came from the facility, the national PV
center or another source, almost a third of the health facilities indicated that the average time
from ADR signal generation to communication to HCWs and the public was less than three
weeks. Just over 20% of the facilities had conducted at least one training or patient education
program related to medicine safety in the last year. Fourteen percent had received and
addressed at least one medicine safety information request per month in the previous year.
As indication of health facilities effectiveness in addressing medicine safety issues at the level
of service delivery beyond basic reporting, approximately one-fourth of the total facilities
reported that they had taken medicine safety action (other than reporting the ADR) in the last
one year to inform clinical management, guideline revisions, regulatory decisions, or health
worker and patient education. Eight facilities (9%) had identified medicine safety issues of
local relevance from outside sources and acted on them locally in the last year (table 34).
Table 34. Results of Risk Management and Communication at Service

Delivery Level
Use prequalification schemes in medicine procurement >33%
Sampled and analyzed >95% of medicines for product quality 16%
Have risk mitigation plans in place for high risk ADR medicines 20%
Received medicines safety bulletins from national PV centers ~25%
Indicated average time from ADR signal generation to communication to ~33%
HCWs < 3 weeks
Conducted training or patient education programs ~20%
Received and addressed at least one medicine safety information per month 14%
in previous year
Reported taken medicine safety action (other than reporting ADR) to inform ~25%
clinical management
Identified medicine safety issues of local relevance from outside sources 9%
Pharmacists’ role in the community and direct interaction with patients makes pharmacies
an important source of information for patients. It is therefore important that they receive
all pertinent medicine safety information, from the national PV center or MoH as well
as from industry, so that they can act and inform patients accordingly. Only three private
pharmacies in the assessment (5%) reported that they had received and addressed at least
one medicine safety information request per month last year. Nearly a quarter (27%)
received medicine safety bulletin (from the PV center or any other stakeholder, including
industry) in the past year.
The same percentage of pharmacies was aware of strategies or plans (such as a medication
guide) being implemented to mitigate and restrict the use of high-risk medicines due to
safety concerns. Although the pharmacies’ awareness of any public and community education
activities on ADRs and medicine safety topics was 27%, nearly two-thirds (63%) who
acknowledged to have received safety alerts, were aware of at least one medicine safety action
other than ADR reporting, such as those taken by the regulatory authority or government
institution as well as by pharmaceutical companies. The assessment findings indicate that
private pharmacies’ role in the national PV system has not been adequately realized in any
of the five countries and that tremendous opportunity exists to engage them more fully and
actively and maximize the benefits of their face-to-face interactions with patients, not only in
terms of reporting but also in terms of disseminating information and educating the public.
Table 35. Results in Private Pharmacies Surveyed at Service Delivery Level

Received and addressed at least one medicine safety information request 5%
per month last year
Received medicine safety bulletin in past year ~25%
Pharmacies aware of strategies or plans being implemented to mitigate and ~25%
restrict use of high risk medicines
Pharmacies awareness of public and community education activities on ADRs 27%
Pharmacies aware of at least one medicine safety action other than ADR 63%
reporting to inform clinical management
PV Capacity at the Health Facility Level

Figure 5 below illustrates not only the overall deficiencies in the functioning and capacity
of health facilities within the PV systems assessed but also the substantial differences
between countries. Although Thailand’s health facilities have some shortcomings, they are
currently functioning, and have the capacity to function at a notably higher level than the
health facilities in the other countries. The health facilities in both Bangladesh and Nepal
are contributing only minimally to the PV systems in their respective countries. It is notable
that the strongest component of the PV system at the health facilities in all the countries was
the systems, structure, and coordination component. This suggests that they have some of
the means to improve the other components. Figure 6 depicts the PV system in private and
community pharmacies in the five countries. Performance across all components of the PV
system is weak however Philippines (awareness of existence of policy and regulations) and
Thailand (risk assessment and evaluation) perform better than other countries.
Discussion
PV activities at the health services delivery points is very weak across all countries studied.
From poor availability of adverse events reporting forms to lack of budget for PV-related
activities, non-functional DTCs, no trainings, and lack of medicine safety information, it
appears that PV is failing at the point where it is required the most—the interface between
the health providers and patients. Clearly ensuring medicines safety to protect the patient
Figure 5. PV Capacity at the Health Facility Level
Health Facilities Policy, Law, Regulation,
and Governance
100%
80%
60%
Risk Management 40%
and Stakeholder
and Communication
20% Coordination

Figure 6. PV Capacity in Private and Community Pharmacies

Pharmacies Policy, Law, Regulation,
and Governance
100%
80%
60%
Risk Management 40%
and Stakeholder
and Communication
20% Coordination
0%

and ensure optimal treatment outcomes is merely receiving adequate attention. The
implications are that patients are exposed to preventable harm. Many high-risk medicines
are in the national register of all the countries studied. For instance, biologics medicines
(including abatacept, adalimumab, infliximab, rituximab, tocilizumab that are indicated for
rheumatic diseases and trastuzumab and bevacizumab indicated for cancers) are in countries’
national registers and used in some of the health facilities. Yet these facilities do not have
guidelines for managing high-risk medicines and some do not have a medication safety or
quality assurance staff. The use of medicines utilization reviews, risk management, and risk
communication to the patient can help to make PV contributions to improvements in health
outcomes more easily recognized. The successes achieved in establishing PV systems at the
national levels should be followed through to the services delivery levels.
Options for Improving PV at the Service Delivery Level (Health
Facilities and Community Pharmacies)
Inform Health Workers on the Value of PV
Healthcare providers are the bedrock for the identification of new concerns on the safety
and effectiveness of medicines. Most of the important observations that led to the removal of
harmful products from the market, including the case of thalidomide came from case reports
from diligent physicians and other health workers. If health workers are trained to appreciate
the contributions adverse events reporting can make to safeguard the patients, it may help to
stimulate interest in PV.
Streamline Adverse Events Reporting

Unfortunately, the current spontaneous reporting system is laden with systematic and
logistical challenges that need to be reformed to ensure health worker participation. The
current reporting system is burdensome for the busy clinicians and the system does not
motivate the reporter. A reporter who has taken the time to observe and send reports on
an event is presumably interested in knowing about the outcome of the investigations and
the next cause of action. Also in the medical records in most countries, the reasons for the
switching or stopping of therapies are often noted. Health workers should be informed of the
dual actions required when adverse events occur in clinical care; recognize and manage the
event (clinical PV), and report the events (regulatory PV). Countries should consult with
health workers in open forums to discuss on the best approaches for improving the roles of
the staff, the health facilities, and their committees in PV.
Develop In-Service Training Curriculum on PV

Countries should consider options for developing in-service PV curriculum and incorporate
it into health workers’ regular trainings.
Transcribe Data from Patient Files

The study found that in many health facilities adverse events may be more commonly
reported in patients’ files as justification for treatment switches. Health facilities should
collaborate with the national PV program to transcribe these events from the patient records
and submit them to the PV center.
Strengthen DTCs
In most of the countries medicines utilization reviews are rarely conducted—a key role for
the DTCs. Countries should consider options for strengthening the DTCs including making
the committee’s activities part of the performance indicators for doctors, pharmacists, and
nurses.
PV Results in
the Pharmaceutical Industry
The assessment included five clinical research organizations, seven medical device companies,
and 38 pharmaceutical companies, including multinational innovator, multinational generic,
and local innovator and generic manufacturers.

Legal provisions and policy statements at the national level dictate the medicine safety
regulations to which the pharmaceutical industry is required to adhere. Pharmaceutical
industries are therefore encouraged to develop policies and procedures that define how they
plan to ensure compliance to the national laws and policies. The assessment found that 29
of 38 pharmaceutical companies (76%), 5 of 7 medical device companies (71%), and 5 of
5 clinical research organizations (CROs) (100%) have updated internal policy statements
on PV or medicine safety within the last five years. Fewer industry reported procedures
to ensure compliance with national laws, as only 23 of 38 pharmaceutical company (61%),
4 of 7 medical device company (57%), and 1 of 5 CRO (20%) have SOPs to address PV
and medicine safety in the quality system of the company, procedures that mention legal
provisions for PV/medicines safety, and the submission of PSURs as required in country.
Only Cambodia and the Philippines were found to have laws requiring market authorization
holders to report serious ADRs to the NRA, and only Philippines and, to a limited extent,
Thailand require post-market surveillance.
Whereas only Cambodia, Philippines, and Thailand (through the SMP program) has
mandatory reporting requirements for the industry, the assessment found that 25 of 35
pharmaceutical companies (71%), 7 of 7 medical device companies (100%), and 3 of 5 CROs
(60%) studied had mandatory reporting requirements for ADRs within the company.
Another 28 of 35 pharmaceutical companies (80%), 3 of 7 medical device companies (43%),
and 2 of 5 CROs (20%) reported mandatory requirements to conduct post-marketing
surveillance. This discrepancy is likely due to global reporting requirements among
multinational respondents who are required by SRAs to mandatorily report ADRs in
countries where they market the product. All but two of the industry respondents reported
procedures for addressing product quality assurance. Most have procedures for addressing
PV or medicine safety information in advertising and promotional materials (32 of 38
pharmaceutical companies [84%] and 6 of 7 medical device companies [86%]).

Among industry representatives studied, 25 of 38 pharmaceutical companies (66%), 4 of 7
medical device companies (57%), and 4 of 5 CROs (80%) have a PV or medicine safety unit,
either as a stand-alone unit or a subset, assigned responsibility for monitoring medicines
safety. Of those, roughly half within pharmaceutical and medical device companies were
found to be fully operational with a clear mandate, structure, delineation of roles and
p v r e s u lt s i n tthhee pphhaarrmac
maceeuutti c
i caall i n ry
i ndduussttry 89
Table 36. Results of Policy, Law and Regulation in the Pharmaceutical Industry
Pharmaceutical Medical device Clinical research
companies, % companies, % organizations, %
Updated internal policy statements 76 71 100
on PV
PV procedures 61 57 20
Mandatory reporting requirements 71 100 60
for ADRs
Mandatory requirements to conduct 80 43 20
post-marking surveillance
Procedures for advertisements 84 86 n/a
responsibilities; have implemented PV-related activities in 2011; PV inspections conducted

within the last five years and reports generated; and procedures for PV audits and inspections
in the companies’ quality systems. Industry representatives that reported having at least one
staff member designated responsibilities for PV and medicines safety came from 30 of 38
pharmaceutical companies (79%) and 5 of 7 medical device companies (71%).
Nevertheless, funding for PV within industry sampled was found to be limited. Only 19 of 37
pharmaceutical companies (51%) and 3 of 7 medical device companies (43%) had dedicated
funds available for PV-related activities in 2011. Less than half of the pharmaceutical and
device companies reported having SOPs for PV and medicine safety both in place and
followed (18 of 38 pharmaceutical companies [47%] and 3 of 7 medical device companies
[43%]), though 4 of 5 (90%) of CROs reported have such SOPs in place. Quality control units
were found to be present and functional in 24 of 37 pharmaceutical companies (65%) and 6
of 7 medical device companies (86%) studied.
Communication technologies for PV and provision of medicine information was found to be

available and functional in nearly all industry respondents (36 of 38 pharmaceutical company
[95%], 6 of 7 medical device company [86%], 5 of 5 CROs [100%]) and core reference
materials for PV or safety were found to be available in most (28 of 38 pharmaceutical
company [74%] and 6 of 7 medical device company [86%]). In 2011, staff members were
trained on PV and medicine safety in 28 of 38 pharmaceutical company (74%), 6 of 7 medical
device companies (86%), and 4 of 5 CROs (80%). When ask if they have system for preparing
for PV inspections and if they have had an audit of the PV quality management system in the
past 5 years, 63% of companies answered yes.
Table 37. Results of Systems, Structures, and Stakeholder Coordination in Pharmaceutical Industries
PV unit 66 57 80
At least 1 staff member designated responsibilities for PV 79 71 n/a
Dedicated funds available for PV 51 43 n/a
SOPs for PV in place 47 43 90
Quality control units 65 86 n/a
Have functional communication technologies for PV 95 86 100
Have core reference materials 74 86 n/a
Staff trained on PV 74 86 80
Among industry representatives studied, 16 of 38 pharmaceutical companies (42%), 4 of 7
medical device companies (57%), and 2 of 5 CROs (20%) reported being fully engaged in
the generation of medicines safety signals. This includes a system for archiving and storage
of medicine safety-related documents with transmitted data, a system that is ICH E2B
compliant and tracks activities and workload; sufficient capacity for electronic submission of
ADR reports to the NRA, and databases that use standard terminologies (i.e., MedDRA). The
assessment found significant deficiency regarding use of the national ADR form. Although
the national ADR form is readily available within each country, 15 of 38 pharmaceutical
companies (39%), 3 of 7 medical device companies (43%), and 3 of 5 CROs (80%) did
not have AE reporting forms available. Twenty-seven out of thirty-eight pharmaceutical
companies [71%], 2 of 5 CROs [40%]), medical device error (1 of 7 medical device companies
[14%]) has product quality reporting forms. For lack of efficacy (17 of 38 pharmaceutical
companies [45%]) have reporting forms and none of the CROs have treatment failure forms
(0 of 5 CROs).
Table 38. Availability of Forms in Pharmaceutical Industry

Product quality 71 14 40
Medical device error n/a n/a
Lack of efficacy 45 n/a n/a
Treatment failure n/a n/a 0

Industry contributes to the risk assessment and evaluation of medical products by detecting
safety signals for further evaluation and conducting studies such as Phase IV post-marketing
surveillance studies, in the event that product safety profiles are incomplete or otherwise
require further assessment and evaluation. Among the companies included in the assessment,
it was found that less than half of pharmaceutical companies (16 of 38 pharmaceutical
companies [42%]) and just more than half of medical device companies (4 of 7 medical
device companies [57%]) and CROs (3 of 5 CROs [60%]) collected spontaneous ADR reports,
put them in a database, and transmitted to the local NRA. In 2011, causality was determined
for the majority of the records in the database in only a third (13 of 38) of pharmaceutical
companies surveyed.
Pharmaceutical industry plays an important role in validating medicine safety signals of

concern through post-marketing surveillance and product quality assurance activities.
However, only a small percentage of industry conducted these types of activities in 2011. Two
of 38 pharmaceutical companies (5%) and 2 of 7 medical device companies (29%) conducted
product quality surveys; none and 3 of 7 medical device companies (4%) but none of the
38 pharmaceutical companies conducted surveys of medication/device errors , and, 6 of
38 pharmaceutical companies (16%) and none of the medical device companies conducted
medicine/device utilization reviews. Within the last five years, active surveillance activities
were reported to be conducted in 15 of 38 pharmaceutical companies (39%), 4 of 7 medical
device companies (57%), and 1 of 5 CROs (20%) sampled (table 39).
p v r e s u lt s i n t h e p h a r mac e u t i c a l i n d u s t ry 91
Table 39. Results of Risk Assessment and Evaluation in Pharmaceutical Industry
Collect spontaneous ADR reports 42 57 60
Conduct product quality surveys 5 29 n/a
Conduct medication/device error 0 43 n/a
surveys
Conduct medication/device 16 0 n/a
utilization reviews
Conduct active surveillance activities 39 57 20
n/a denotes not applicable and that the indicator was not assessed

The assessment found that industry was an important source of medicine safety information
among healthcare providers, pharmacists, and consumers. Medicine/device safety
information requests were received and addressed at least once per month in 2011 in 12 of
38 pharmaceutical companies (32%), 2 of 7 medical device companies (29%), and 2 of 5
CROs (20%). A fifth of the pharmaceutical companies surveyed (8 of 38; 21%) reported the
publication of medicine safety alerts in 2011.
Locally implemented risk mitigation plans that require EU or United States mitigation
strategies to control distribution and use of high-risk medicines because of safety concerns
was reported in 8 of 38 pharmaceutical companies (21%), and 3 of 5 CROs (60%); none of
the 7 medical device companies issued reports. Medicine and medical device safety issues
of local relevance were identified from outside sources and acted on locally in 2011 in 7 of
38 pharmaceutical companies (18%), 1 of 7 medical device companies (14%) and 2 of 5 CRO
(2 %). Medicine safety information was reported to have been communicated promptly to
healthcare workers and the public by nearly half of the pharmaceutical companies sampled
(18 of 37; 49%), 2 of 7 medical device companies (29%) and 2 of 5 CROs (20%). Industry
was aware of medicine safety action taken by the NRA (e.g., dear doctor letters) to inform
clinical management, guideline revisions, regulatory decisions or health worker and patient
education in 22 of 38 pharmaceutical companies (58%), 7 of 7 medical device companies
(100%), and 2 of 5 CROs (20%).
Discussion
In the countries assessed, the pharmaceutical industry’s engagement in medicine safety
and product quality activities and involvement in their respective national PV systems
are limited and do not fulfill the full potential of industry’s role in ensuring the safety of
pharmaceutical products and devices for patients. As the pictorial depictions of PV capacity
in the pharmaceutical industry demonstrate (figures 7-9), industry performance across the
five countries differ considerably, with Nepal showing the least capacity and Bangladesh,
the Philippines, and Thailand showing comparably higher levels of capacity. Across all five
countries and all three types of industry representatives—pharmaceutical companies, medical
device companies and CROs—the lowest levels of capacity in the pharmaceutical industry are
in the areas of risk assessment and evaluation and risk management and communication.
The pharmaceutical industry’s limited involvement in PV activities is partly due to the

inadequacies of national policies, laws, and regulations. Some laws and regulations do
Table 40. Industry PV Capacity and Activities
Multinational Multinational Local
innovator generic manufacturer Total
PV-related capacity and activities (n = 12) (n = 12) (n = 14) (N = 38) N, %
PV unit or staff 8 11 10 29 76
PV SOP 9 10 7 26 68
> 5% of staff trained on PV in 2011 10 11 7 28 74
Adverse event reporting form 9 9 7 25 66
Product quality reporting form 9 9 10 28 74
Treatment failure reporting form 8 5 8 21 55
Collected ADR reports in 2011 9 9 7 25 66
Sent ADR reports to regulatory 6 5 4 15 39
authority in 2011
Carried out post-marketing / active 3 7 5 15 39
surveillance in 2011
Responded to PV information requests 3 5 3 11 29
in 2011
Published and distributed medicine 1 4 3 8 21
safety bulletins in 2011
Submitted and implemented risk 3 3 1 7 18
management plans locally
Communicated AEs to HCW and public 9 6 5 20 53
in < 3 weeks
Changed labels, package inserts, or box 6 4 7 17 45
warnings in 2011
Figure 7. PV Capacity in Pharmaceutical Companies
Pharmaceutical Policy, Law, Regulation,

Companies and Governance
100%
80%
60%
Risk Management 40%
and Stakeholder
and Communication
20% Coordination
0%

Figure 8. PV Capacity in Device Companies
Device Companies Policy, Law, Regulation,

and Governance
100%
80%
60%
Risk Management 40%
and Stakeholder
and Communication
20% Coordination
0%

Figure 9. PV Capacity in Clinical Research Organizations
Clinical Research Policy, Law, Regulation,

Organizations and Governance
100%
80%
60%
Risk Management 40%
and Stakeholder
and Communication
20% Coordination
0%

not require the industries to play a more active role through mandatory post-marketing
surveillance, AE reporting, and product quality reporting and quality management, or the
regulations are not effectively enforced. In the absence of legal provisions for safety and
quality monitoring in some countries, industry is in a position to determine which PV-
related activities serve their best interests, which tend to be more profit-driven and less
public health-driven. To the extent that the pharmaceutical and medical device companies
and CROs included in this study are implementing PV activities, the activities appear to be
happening in parallel with the national PV system rather than as an integrated part of it.
Opportunities exist across all study countries for governments to strengthen their regulation
of industry and to improve and expand their PV activities to contribute to the public good
and give them a competitive advantage in the marketplace based on their compliance with
international standards.
Options for Improving PV in Pharmaceutical Industries

Strengthen Industry Commitment to PV
The pharmaceutical industry is not doing enough to support PV activities in the countries
studied. For instance, because there are limited provisions that require product sponsors to
conduct the same or similar post-marketing surveillance activities for products as required
by SRAs, the pharmaceutical industry operating in the countries do not conduct these
activities. In the absence of adequate legislation and enforcement, due diligence and product
stewardship should drive the industry to meet these requirements locally as they do in better
regulated markets.
Implement Risk Management Plans

The industry should implement or offer to implement (where legal requirements do not exist)
harmonized standards for risk management plans (RMPs) as they have with the EMA and
other European competent authorities. The RMP should include safety specifications and PV
plans in accordance with ICH E2E and a risk minimization plan. Industry should routinely
scan worldwide safety literature and ensure that safety issues identified from outside sources
for a product that is registered locally is promptly communicated to the NRA and consumers.
Improve Adverse Events Reporting

The pharmaceutical industry should strengthen their adverse events reporting system. They
should have a staff responsible for PV, develop ADR report database that uses either the E2B
or CIOMS I form, train all marketing staff members on the need to report, ensure ethical
promotion, and conduct internal PV audits.
Implement PV Audits and Inspections

The industry should be proactive in addressing its responsibility for product stewardship and
should collaborate with the NRAs to institute PV inspections.
Collaborate on Device Regulation and Vigilance

Among the countries studied, Cambodia, Philippines, and Thailand are members of the
AHWP. Besides support for device classification and registration based on risk, industry
should collaborate with the AHWP to support members and non-members within the region
to develop strong device vigilance system as high-risk medical devices are increasing being
used in these countries. From our study, device vigilance systems were not really functioning
in the countries. For instance, when we asked if a form exists for spontaneous reporting of
suspected device adverse events, we found that there are no forms in Cambodia, Nepal, and
Thailand. Countries can start with adopting the Global Harmonization Task Force Medical
Devices Post Market Surveillance: Global Guidance for Adverse Event Reporting for Medical
Devices (GHTF 2006).
PV Results at
the Civil Society Level
Civil society entities included in the assessment include consumer groups (n = 10),
professional organizations such as medical, pharmacy, nursing, health professionals, and
chemists (n = 22), and medical and pharmacy academia (n = 22).

Among the consumer groups and medical professional associations assessed, few respondents
reported awareness of the existence of a national policy for monitoring and reporting adverse
events (20%) and 27% of professional associations or laws and regulations for monitoring and
reporting adverse events (10% consumer groups) and 9% of professional associations [9%]).
Table 41. Results of Policy, Law, and Regulation at Civil Society Level
Indicator Consumer groups Professional associations
Aware of existence of national policy for 2/10 (20%) 6/22 (27%)
monitoring ADRs
Aware of existence of laws and regulations 1/10 (10%) 2/22 (9%)
for monitoring ADRs

The assessment found that about half of the professional associations studied reported
having a member who is aware of the national PV center. Eighty percent of consumer
groups reported that patients and consumers are unaware of the national PV center. Both
consumer groups and professional associations reported low awareness of any service to
ask questions related to ADRs and medicine safety—30% of consumer groups and 2 of 22
professional associations (9%). In Thailand and Cambodia, where national PV guidelines are
in place, 4 of 5 (80%) professional associations reported awareness of the guideline, though
no consumer groups reported awareness of the PV guideline. The assessment also found that
consumer groups consistently reported a role in ensuring medicine safety in their country
(80%) as did, albeit to a lesser extent, professional associations (55%). Out of 10 consumer
groups and 22 professional associations studied, members from three (30%) and eight (36%)
respectively serve on the national safety advisory committee in Bangladesh, Cambodia, and
the Philippines. PV and medicine safety topics are taught in medical, pharmacy, nursing, and
continuing education programs in 5 of 22 (23%) professional associations and 15 of 22 (68%)
academic institutions studied. Healthcare professionals affiliated with 1 of 10 (10%) consumer
groups and 10 of 22 (45%) professional associations received training in PV topics in 2011.
Academic institutions studied reported awareness of a platform or a forum for coordination
of PV activities across all stakeholders and viewed academia as an important stakeholder in
ensuring medicine safety in their country (15 of 22 [68%]).
p v r e s u lt s at tthhee cci vi vi li l ssoocci ei ettyy lleevveell 97

Table 42. Results of System, Structure, and Stakeholder Coordination at
Civil Society Level
Indicator Consumer groups Professional associations
Member of the association is aware of n/a 10/22 (45%)
national PV center
Patients and consumers unaware of PV 4/5 (80%) n/a
center
Aware of any service to ask questions 3/10 (30%) 27
related to ADRs
Aware of PV guideline 0 80
Reported role in ensuring medicine safety 8/10 (80%) 12/22 (55%)
Received training in PV 10 45

The assessment found that patient and consumer awareness of mechanisms to directly report
medicine safety concerns to national PV centers was limited. In Thailand and the Philippines
where a national consumer reporting form is available to consumers, only 2 of 7 (29%)
consumer groups reported that patients and consumers are aware of a national consumer
reporting form and encouraged to report directly to PV center.

The assessment found that some risk assessment and evaluation activities were undertaken
by academic institutions in the countries studied, including product quality surveys (5 of 22
[23%]), medication errors studies (5 of 22 [23%]), and medicine utilization studies (4 of 22
[18%]) all in 2011, and active surveillance activities (8 of 22 [36%]) in the last five years.

The assessment found that the majority of professional associations were aware of medicine
safety actions taken in country and thereby in a position to inform members. Although more
than half of the professional associations reported receiving some sort of medicine safety
bulletin in 2011 (12 of 22 [55%]), the same was reported by only a fifth of consumer groups.
Respondents were found to be aware of strategies or plans, such as medication guides, to
mitigate and restrict the use of high-risk medicines in 11 of the 22 professional associations
studied and 2 of 10 of the consumer groups. Trainings in medicines safety topics were
conducted in 2011 in a fifth of the consumer groups studied (2 of 10 consumer groups [20%])
and nearly a third of professional associations (14 of 22 PA [64%]). Respondents were aware
of medicines safety action taken other than ADR reporting in 2011 in 3 of 10 consumer groups
(30%) and 14 of 23 professional associations (61%).
PV Capacity in Civil Societies

In general, consumer groups make minimal contributions to the strength of the overall PV
system, with notable exceptions in Bangladesh and the Philippines. Professional associations
seem to have a greater influence, especially in Thailand.
Figure 10. PV Capacity in Consumer Groups
Consumer Group Policy, Law, Regulation,

and Governance
100%
80%
60%
Risk Management 40%
and Stakeholder
and Communication
20% Coordination
0%

Figure 11. PV Capacity in Professional Associations
Professional Association Policy, Law, Regulation,

and Governance
100%
80%
60%
Risk Management 40%
and Stakeholder
and Communication
20% Coordination
0%

Discussion
Civil society has a significant role to play in PV systems both as a participant and beneficiary.
The study results indicate that civil society is a relatively inactive group, and thus untapped
resource, within the PV systems assessed. Awareness of PV services and activities, including
the policies, laws and regulations that establish the legal mandate for them, is low, especially
among consumer groups. Civil society partners’ participation in their respective national PV
systems and other PV-related activities is also very limited, even where PV systems provide
an established mechanism for participation and the groups see a role for themselves in their
country’s PV system. Low consumer reporting rates in the two countries that have consumer
reporting forms—the Philippines and Thailand—suggest that providing opportunities
p v r e s u lt s at t h e c i v i l s o c i e t y l e v e l 99
and mechanisms alone does not ensure participation or even awareness and that more
targeted efforts are needed to engage these partners. Professional associations and academic
institutions, in particular, have a great deal to contribute to regional PV given the existing
mechanisms for engaging medical and pharmacy professionals and researchers in PV efforts.
For instance, academic institutions have research and training capacity, as well as specialized
expertise, which are essential for effective PV. Governments and civil society groups
themselves can be doing more to ensure that civil society is helping to improve and expand
generating and disseminating information related to medicine safety.
Options for Improving PV in Civil Societies

Improve the Visibility of PV as a Public Health Priority
Civil society’s active involvement in PV systems depends not only on awareness of the
legal mandate, structures and systems for PV in the country but also on the society’s
understanding of its importance and how it affects them. The recommended starting point
for engaging civil society is improving the visibility of medicine safety as a matter of public
health importance and motivating members to get involved. The national PV center and the
services it offers should also be made more visible to targeted groups and the general public,
so that people know where to get and to provide information related to medicine safety and
quality. Media campaigns and public service announcements that communicate key messages
through multiple channels and platforms are good ways to help raise awareness.
Establish Accessible, User-Friendly Forms and Mechanisms for Civil

Society Groups
Consumer reporting is an important source of information on suspected medicine safety
and quality problems within a well-functioning PV system. In countries without consumer
reporting forms, national PV centers are encouraged to develop a simple form designed
specifically for that group. An effective consumer reporting form will capture only the
essential information and will be clear and easy to fill out even for those individuals with
low literacy and no background or training in a health-related field. Establishing easy
mechanisms or platforms for consumer reporting, including the submission of forms, is also
important for countries to improve the quality and frequency of reporting. Call centers or
hotlines and websites, for instance, can help consumers submit information on medicine
safety. In recognition that phone and internet services are limited among some populations
in the region, more basic mechanisms can be established as well, including paper submissions
direct to clinics and pharmacies, which can transmit the information to the PV center on the
behalf of the patients and consumers.
Establish Collaborations with Academic Institutions for PV-Related

Activities
Many academic institutions are already involved in PV-related activities, such as training for
pharmacy and medical students and research on medicine use, safety, and quality. However,
the results of their work are not always shared with or channeled through the national PV
system and to the public. By establishing formal memorandums of understanding and setting
up opportunities for effective coordination and communication, academic institutions
and national PV programs can share resources and information, strategically divide
responsibilities according to comparative advantage, and together make a greater impact.

Comparison of Performance
and Capacity of PV in
Selected Asia Countries
A comprehensive PV system is comprised of (1) governance, policy, law, and regulation, (2)
system structure and stakeholder coordination; (3) signal generation and data management,
(4) risk assessment and evaluation; and (5) risk management and communication. WHO
defines the minimum requirements for a functional national PV system as having a national
PV center, a spontaneous reporting system, a national database, a national PV advisory
committee, and a communications strategy (WHO 2010c). To build on these minimum
requirements and highlight the need for providing further details and indicators for
monitoring all aspects of comprehensive PV systems and benchmarking these systems’
performance, we developed the systems classification.
Methods
Using a set of indicators addressing all of the five PV components, SIAPS developed criteria
for classification of countries into four groups. Tables 43a and 43b list the criteria for systems
classification into these groups at the national level. Country-specific data for all indicators
can be found in annex C. The groupings represent the level of achievement of countries in
meeting the relevant indicators in a PV system.
The scoring of the classification scheme is as follows: core indicators are given 2 points
each and the rest of the indicators are given 1 point each. The score of the indicators met is
divided by the total score of all the indicators and multiplied by 100; if this value is >60% for
each component, the country is said to meet the standard requirements for that component.
The limitations in this scoring method are recognized. We do not have an explicit criteria
or reference for the 60% cut off; establishing how well these PV components function
is challenging, and even though responses were verified, the study data may still not be
sufficient to determine the robustness and sustainability of countries PV system. However,
this scoring facilitates easy recognition of where countries are working toward a functional
PV system. Also achieving 60% in the PV components for resource-limited settings may be a
reasonable expectation.
Similar to the approach used in an SPS report (Strengthening Pharmaceutical Systems (SPS)
Program 2011), countries are classified into four groups based the capacity and performance
of their PV systems—
§§ Group 1: Countries have no capacity or have minimal organizational structures and

capacity for PV. Though there is relevant pharmaceutical legislation, there are no
specific legal or structural frameworks for PV systems, and no coordinated passive or
active surveillance in these countries. Any ongoing PV activities take place without
national coordination. Bangladesh and Nepal belong to Group 1.
co m pa r i s o n o f p e r f o r ma n c e a n d c a pac i t y o f p v i n s e l e c t e d a s i a co u n t r i e s 101
Table 43a. Classification Scheme for PV Capacity
PV component Group 1 Group 2 Group 3 Group 4
Policy, law, and regulation N Y Y Y
System, structure, and stakeholder
N Y Y Y
coordination
Signal generation and data
N N Y Y
management
Risk assessment and evaluation N N Y Y
Risk management and communication N N N Y
Table 43b. Performance Card

Policy, law, regulation,
X X X X X
and governance
Systems, structures,
and stakeholder X X X
coordination
Signal generation and
X X
data management
Risk assessment and
X
evaluation
Risk management and
X X X
communication
Group Group 1 Group 2 Group 1 Group 3 Group 4
§§ Group 2: Countries have basic structure in place. The countries have policy and legal
frameworks for PV. Additionally, most basic organizational structures, such as an
institution with a clear mandate for PV, guidelines, and SOPs; a reporting form, and
a safety advisory committee, are in place. Stakeholders’ roles and responsibilities are
recognized but not fully coordinated. The capacity to generate signals and evaluate the
risks is limited in these countries. The spontaneous reporting system does not cover
all sources of medicines-related problems. The PV system lacks active approaches to
evaluate signals and implement effective risk management practices. Cambodia belongs
to Group 2.
§§ Group 3: Countries have the capacity to collect and evaluate safety data on the basis
of legal and organizational structure. The countries have organizational structure and
policy framework to collect and collate safety data in a national database and evaluate
the risks and benefits by both passive and active approaches. However, the capacity to
manage the risks by taking appropriate preventative actions, develop a plan to actively
monitor the risks, and communicate with stakeholders is lacking. The Philippines is
classified as being in Group 3.
§§ Group 4: Countries have performing PV systems to detect, evaluate, and prevent

medicine safety issues. The countries have the basic structures, both passive and active
surveillance activities, and the capacity to evaluate the risks. Based on these, outcomes
of PV activities inform regulatory actions and are communicated to stakeholders. It
is unclear if the current situation will be sustained over time. Thailand is classified as
being in Group 4.

Global and Regional
Initiatives for Strengthening
Pharmacovigilance
Systems in Asia
A multitude of global, regional, and in-country institutions and programs are contributing to
the strengthening of PV systems throughout Asia. Coordinating these efforts and establishing
and strengthening links between them provides opportunities to maximize effectiveness and
achieve greater impact through improved funding, technical support, capacity building, and
information sharing.
Financing Institutions
The Global Fund has made strengthening PV a funding priority and encourages countries
to include PV activities in its grant proposals and activities (Xuaref S, Daviaud J 2013). Prior
to round 10, a total of six grants in the SEARO and WPRO regions had PV activities in
progress. Under round 10, five grants in the two regions had PV activities planned: Indonesia
(TB), Laos PDR (TB), Nepal (HIV and AIDS), Thailand (TB), and Vietnam (health system
strengthening) (Lalvani 2012).
Bilateral donors, namely the European Commission and USAID, are also contributing
targeted funding for PV in the region. Since 2010, the European Commission, in
collaboration with WHO-UMC, has been supporting the Monitoring Medicines program,
which focuses on improving consumer reporting, supporting countries to expand the scope
of their PV activities, promoting improved use of existing global PV data, and developing
focused surveillance methods in select countries (Uppsala Monitoring Centre). USAID funds
two programs—Systems for Improved Access to Pharmaceuticals and Services (SIAPS) and
Promoting Quality of Medicines (PQM)—that provide technical assistance to developing
countries, including many in Asia, to strengthen their medicine safety and quality monitoring
systems under PEPFAR and PMI.
Other financing institutions that are supporting targeted PV initiatives globally and in the
region include the Bill & Melinda Gates Foundation, GAVI alliance, and UNITAID.
Technical Institutions and Programs

WHO provides global technical leadership in PV by providing norms, standards, and other
forms of guidance that are developed across various departments and disease-specific
programs (WHO). The WHO Advisory Committee on the Safety of Medicinal Products,
made up of experts from the drug evaluation and drug policies and management advisory
panels, provides advice on pharmaceutical safety issues for member states in all regions. In
addition to disease-specific PV activities in HIV and AIDS, tuberculosis, malaria, and Chagas
disease, WHO also focuses on vaccine safety (WHO).
g lo b a l a n d r e g i o n a l i n i t i at i v e s f o r s t r e n g t h e n i n g p h a r maco v i g i l a n c e s ys t e m s i n a s i a 103
UMC reviews and analyzes new ADR signals from the case report information submitted to
the WHO ICSR global database (VigiBase) by national PV centers; strengthens information
sharing through the publication of periodicals and newsletters; supplies national centers with
tools, including computer software; and provides training and consultancy support (Uppsala
Monitoring Centre).
Other international institutions providing general and disease-specific technical support

and guidance in the area of PV in the Asia region include CIOMS, International Society of
Pharmacovigilance, ICH, International Pharmaceutical Federation, Management Sciences for
Health, Médecins Sans Frontières, and United States Pharmacopeia.
Vaccine safety is receiving specific attention from such organizations as Brighton

Collaboration and the US FDA’s Center for Biologics Evaluation and Research, which
launched the Global Regulatory Utilization of Vaccine Safety Surveillance initiative in 2012
(Brighton Collaboration; USFDA). Organizations addressing PV in the context of new
product development include the Drugs for Neglected Diseases Initiative, Medicines for
Malaria Venture, and the Product Development Partnership Access Group (“Drugs for
Neglected Diseases Initiative”; “Medicines for Malaria Venture”; “PDP Access Group”).
Regional Institutions
The ASEAN pharmaceutical product working group has created the PMA system as part
of the mutual recognition arrangement and overall harmonization effort in the region.
The types of information shared in the alerts include product withdrawals, cancellations of
registration and suspensions of sales, adulteration with pharmaceutical ingredients, quality
issues, product label changes, and others.
The nonprofit organization Pan-Asian Clinical Research Association has established the
PV Asia Network as a platform for PV professionals to network and exchange experiences,
expertise, and information throughout the Asia-Pacific region. It supports the development
and harmonization of PV in the region and incorporates professionals from sponsor
companies, CROs, institutions, ethics committees, health authorities (as permitted by the
regulations of such authorities), as well as related PV organizations (Pan-Asian Clinical
Research Association). A complete mapping of international and regional institutions’ efforts
to strengthen PV globally as well as specifically in the Asia region is presented in annex D.

Conclusion
Great strides have been made in advancing access to medicines in low- and middle-income
countries, thanks to the efforts of global health initiatives and also the increased commitment
of national governments. At the heart of such efforts is ensuring the provision of safe,
effective, and quality medicines. The permeation of products with unknown safety profiles or
of spurious quality into global supply chains and the resulting adverse reactions from their
use can diminish those significant improvements in access and compromise the success of
public health programs that depend on such medicines.
National regulatory authorities (NRAs) are mandated to regulate the development,

manufacturing, and marketing of medical products in their local markets. However, as
the global supply chain grows in complexity, NRAs become increasingly responsible for
protecting not only the local public but also consumers in markets beyond their own borders.
Yet, as found from this study, most of the NRAs have limited capacity in PV. They lack the
regulatory framework and governance structures mandated by legislation and regulations,
including systems for accountability, transparency, and capacity for enforcement to ensure
industry compliance to safety monitoring. Harmonization of regulatory requirements and
international standards reduces duplication and regulatory burden. Countries PV legislations
are not convergent, nor are they consistent with international standards, and discussions
on the adoption of relevant international standards were very preliminary. PV systems and
structures are weak and the ability to generate signals, evaluate them, and use the information
for risk management and communication is limited.
There is a strong and urgent need to strengthen medicine safety systems both within and
across national borders of countries in the Asia region. Developing and developed countries
are both suppliers and recipients within an increasingly complex global medical product
supply chain. Public health programs, global health initiatives, and indeed, entire health
systems rely on safe, effective, and good quality medicines. However, fully functional PV and
regulatory systems are not yet in place. A great challenge and opportunity exist to improve
the systems and capacities required to assure patient safety and to improve health outcomes
in Asia.
co n c lu s i o n 105
Annexes
A. Medication Mishaps And Related Regulatory Forms
B. Pharmacovigilance Profile
C. Country Profiles
D. Assessment Method
E. PV Topics in Curriculum
F. Thailand Health Product Adverse Event Report Form
G. Glossary
annexes 107
Annex A. Medication Mishaps and Related Regulatory Forms
Medication mishaps have helped in defining clearly the primary objective of pharmaceutical regulation which is to
safeguard public health. Though legislation alone cannot resolve the challenges of ensuring safety of medicines, the
examples below highlight the therapeutic mishaps that have catalyzed stricter and more effective medicines regulation.
Those mishaps also contributed to the development of national regulatory authorities and the regulatory policy and
framework that govern their activities.
Year or period Event Related regulatory reforms

1937–2011 About 700 deaths in more than 11 countries due to In the United States led to the enactment of the
diethylene glycol poisoning; index case in US 1937, Federal Food, Drug, and Cosmetic Act (1938) with the
repeated occurrences in Nigeria 1990 and 2008, and premarket notification requirement.
high casualty in Panama where 365 died
1956–1962 About 10,000 children from mothers who were In reaction to this, WHO in 1961 developed the
exposed to thalidomide in Europe/Japan during voluntary notification scheme and in 1961 the World
pregnancy were born with severe malformations Health Assembly requested the WHO
primarily phocomelia.
1999 At least 30 people died in Cambodia after taking No information
counterfeit antimalarials
2004 Up to 140,000 cases of serious heart disease Public criticism of US FDA drug approval and post-
attributed to rofecoxib (Vioxx) marketing surveillance system contributed to the
enactment of the FDA Amendment Act of 2007 which
provided FDA with enhanced statutory authority
regarding post-market safety of drugs
2004–2008 Lack of disclosure of negative clinical trials data, Contributed to the enactment of Section 801 of the
suppression of results, and modification of pre- FDA Amendments Act
specified outcome measures in trials involving Paxil,
Vioxx, and Zetia (ezetimibe)
2005 More than 60,000 people in Niger were inoculated Le Monde reported that the company that made the
with a counterfeit meningitis vaccine resulting in vaccine did not act against the counterfeiters as it
about 2,500 deaths feared that it might damage trade
2009 Mediator® is claimed to be responsible for around The French agency for the safety of health products
3,100 hospitalizations and 1,300 deaths due to (AFSSAPS) was accused of “inexplicably tolerant of a
valvular insufficiency drug with no real therapeutic value.” The Mediator
case led to the resignation of the head of AFSSAPS;
dissolution of AFSSAPS and its replacement by the
National Agency for the Safety of Medicines and
Health Products (MSNA); and enactment of new
legislation to strengthen drug safety in France.
2010 An international police operation led to the seizure Closure of 100 pharmacies and illegitimate drug
of $20M in counterfeit and illegal medicines. The outlets and more than 30 related arrests
operation covered 8 countries in Southeast Asia:
Cambodia, China, Indonesia, Laos, Myanmar,
Singapore, Thailand, and Vietnam
2012 125 patients died from cardiac drug contaminated Pakistan addressed the jurisdictional confusion
with an antimalarial created by the passage of the amendment that
decentralized public health. Federal government
quickly established a central Drug Regulatory
Authority
2012 Committee of the India parliament in its 59th The Ministry of Health and Family Welfare submitted
report accuses the Central Drugs Standard Control Action Taken Report for addressing the identified
Organization (CDSCO) of ‘collusive nexus’ between the weaknesses
industry, CDSCO, and medical experts.

Year or period Event Related regulatory reforms
2012 and 2013 More than 620 people were sickened and 44 Draft bill gives FDA authority over some pharmacies.
died from methylprednisolone acetate injections Bill creates a new class of drug makers called
manufactured by the New England Compounding “compounding manufacturers”
Center (NECC), raising calls for more power for the
FDA for the oversight of drug compounders.
2013 Ranbaxy pleaded guilty to felony charges relating Case instituted against Ranbaxy in India
to the manufacture and distribution of adulterated
drugs and agreed to pay a USD 150 million penalty
and to settle civil claims under the US False Claims Act
and related State laws for USD 350 million.
annexes 109
Annex B. Pharmacovigilance Profile
Governance
Regulatory registers exist Governance structures
Regulatory framework exists (medicines, personnel, mandated by laws and
Country and assessed in last 5 years premises) regulations and in practice
Bangladesh Yes Yes
Cambodia Exists but not assessed Not fully in place
Nepal Exists but not assessed Yes Not fully in place
Philippines Yes Yes
Thailand Yes Yes

Legal provision
mandating MAHs to Legal provision
Policy statements for Legal provision report serious mandating MAHs to
PV or medicine safety for PV exists ADRs exists conduct PMS* exists
Country (year published) (year published) (year published) (year published)
Bangladesh Yes (2005) Yes (1940) No No
Cambodia Yes (2010) Yes (2007) Yes (2011)
Nepal Yes (1995) Yes (1978) No
Philippines Yes (2011) Yes (1987) Yes (2011: PV policy) Yes (1997)
Thailand Yes (2011) Yes (1967) No No
Note: PMS = Post-marketing surveillance
Legal provision for product quality assurance Legal provision for promotion and advertising
Country (year published) (year published)
Bangladesh Yes (1940) Yes (1940)
Cambodia Yes (2010) Yes (2007)
Nepal Yes (1978) Yes (1978)
Philippines Yes (1997) Yes (2008)
Thailand Yes (1967) Yes (1967)

PV center with a clear mandate, structure, QC lab/unit with clear mandate,
Country roles and responsibilities exists structure, functions exists
Bangladesh PV center under NRA; No clear mandate Yes
Cambodia PV center under NRA
QC unit under MOH, not audited
Nepal PV center under NRA; No clear mandate
Philippines
PV center under NRA Yes
Thailand
Medicine information Staff member Dedicated budget National PV guideline

Country service exists for PV (≥1) for PV center exists (year published)
Bangladesh No
Cambodia Yes (2012)
No
Nepal Yes, by PV center Yes
No
Philippines
Thailand Yes Yes

National National
National PV safety advisory quality control advisory Core communication
Country SOPs for PV and QC committee exists committee exists technologies for PV
Bangladesh No No No
No
Cambodia Yes Yes
Nepal No (QC only) No
No Yes
Philippines
Yes
Thailand Yes Yes
Core PV reference material Core PV topics in

Healthcare workers
Country in PV unit/drug pre-service training
trained on PV
information center curricula (> 70%)
Bangladesh Yes Yes (3 of 3 academia) Yes (HF, PHP)
Cambodia No Yes (1 of 2 academia) Yes (NRA, PHP)
Nepal Yes (7 of 7 academia) Yes (PHP)
Philippines Yes (7 of 7 academia)
Yes
Thailand Yes (3 of 3 academia; 2 of 3 Yes (HF, PHP)
professional association)
Mechanism for coordinating WHO International Drug

PV activities across all Monitoring Programme Quality management system for
Country stakeholders exists (year joined) performing PV and QA activities
Bangladesh No Non-member (planned 2013)
Cambodia Official (2012) No
Nepal Official (2006)
Yes
Philippines Official (1995)
Yes
Thailand Official (1984)

Coordination and collation
of PV data from all sources Consumer reporting form Spontaneous reporting form
Country in the country for suspected ADRs for suspected ADRs
Bangladesh No No Yes
Cambodia Yes No Yes
Nepal Yes No Yes
Philippines Yes Yes Yes
Thailand Yes Yes Yes
Product quality reporting form Medication error reporting form Treatment failure reporting
Country (or subset of ADR form) (or subset of ADR form) form (or subset of ADR form)
Bangladesh No No No
Cambodia No No No
Nepal No No No
Philippines Yes Yes Yes
Thailand Yes Yes Yes
annexes 111
Spontaneous reporting > 100 Survey on quality of
per million population per year ICSRs with Causality Assessed pharmaceutical products
Country (no. of reports in 2011) > 50% (% assessed) in the last 1 year
Bangladesh No (0) No (n/a) NRA, academia, PHP
Cambodia No (83) Yes (100%) NRA
Nepal No (35) No (0%) —
Philippines No (3,351) No (35%) Academia, health facilities
Thailand Yes (57,573) Yes (78%) NRA, academia, PHP
Medication error studies Medicine utilization studies Active surveillance activities

Country in the last year in the last year in the last 5 years
Bangladesh Academia, industry,
Academia, PHP PHP, industry, health facilities
PHP, health facilities
Cambodia — NRA —
Nepal — Health facilities Academia, PHP
Philippines Academia, health facilities Academia, health facilities Academia, health facilities
Thailand NRA, PHP, academia, health
Academia Academia
facilities, industry

Medicine safety information Prequalification schemes
requests received and Medicine safety newsletters used in medicine
addressed in 2011 or bulletins planned and procurement decisions
Country (≥ 1 per month) published in 2011 (≥ 70%) (i.e. WHO-GMP, PIC/S)
Bangladesh
No Yes
Cambodia No
Nepal Yes (3 issues/year) Yes (immunization)
Philippines No
Yes Yes
Thailand Yes (1 issue/month)
Medicines sampled No. of medicine safety

Unregistered medicines that were analyzed for Risk mitigation plans issues identified and
in pharmaceutical product quality for high-risk medicines acted on from external
Country market < 3% (% failure) in place sources
Bangladesh No (–) 69% (0.04% failed) No
Cambodia No (est. 30%) 100% (4.6% failed) Yes
0
Nepal 83% (27% failed) No
Yes
Philippines 97.4% (no data)
Yes
Thailand Yes (< 1%) 100% (10% failed) 2

Risk Management and Communication (continued)
Medicine safety regulatory
Time from ADR signal actions taken other than
generation to communication to Public education activities on ADR reporting in last 1 year
Country HCWs and Public <3 weeks ADRs or medicines safety (see key below)
Bangladesh No e, f
No
Cambodia Yes b, h
Nepal No Yes, limited b, c, d, e
Philippines a, d, f, h
Yes Yes
Thailand a, b, d, g, h
a) Label or package insert changes/boxed warning e) Withdrawal of product license
b) Treatment guidelines, medicine formulary, or essential medicine list changes f ) Suspension of marketing authorization
c) MoH memo or circular referencing safety data g) Risk management activities recommended because of new safety data
d) Product recalls h) Dear Dr. letters or safety alerts
annexes 113
Annex C. Country Profiles
Bangladesh
Pharmaceutical Profile
Pharmaceutical Market
Population (2011)* 150.5 million
Gross domestic product per capita (USD, 2011)* 744
Market size: pharmaceuticals (USD, 2011)† 1.5 billion
Market size: medical devices (USD, 2011)† 174 million
Number of medicines registered (2012)‡ 32,245
Total pharmaceutical expenditure per capita (USD, 2006)§ 5.7
Total expenditure on healthcare (TEH) per capita (USD, 2009) || 19
Total pharmaceutical expenditure as a percentage of TEH per capita 31%
Health workforce per 10,000 population (2011)# 0.20
Public expenditure on pharmaceuticals (2006)§ 94.7
Financing mechanisms for pharmaceuticals§ Public (11%), Private/Other (89%)
Medicines Policy
Existence of a national medicines policy National Drug Policy, 2005. MOHFW, Government of the People’s
Republic of Bangladesh†
Legal provision for medicines legislation The Drugs Act of 1940†
Also see the Drug Rules of 1945, the Bengal Drug Rules of 1946,
the Drug (control) Ordinance of 1982, and the Drug Policy of 2005†
Patent provisions (main)** The Constitution of Bangladesh, 2004
Trademarks Act, 2009 (Act No. XIX of 2009) (2009)
The Patents and Designs Act (Act No. II of 1911) (2003)
Copyright Act 2000 No. 28 of 2000 (as amended up to 2005) (2000)
World Trade Organization (WTO) - Agreement on Trade-Related Aspects
of Intellectual Property Rights (TRIPS Agreement) (1994) (January 1, 1995)
Pharmaceutical Production Status
Pharmaceutical manufacturing plants† (allopathic pharmaceutical manufacturing
companies)
* World Bank Database, accessed date 30/08/2012

† Business Monitor International Bangladesh Pharmaceuticals and Healthcare Report 2013
‡ Bangladesh Directorate General of Drug Administration
§ WHO World Medicines Situation 2011 Annex
|| WHO National Health Account Database, 2009
# WHO World Health Statistics 2012
** WIPRO

Pharmacovigilance Profile
Policy, laws, and regulations The Drug Act of 1940

National Drug Policy of 2005
Name of regulatory authority/website Directorate General of Drug Administration
www.dgda.gov.bd
Mandate of regulatory authority Registration, licensing and import control, inspection, QC, PV,
control of promotion, control of clinical trials
How products get into the market Registration by the DGDA, database of registered products available:
www.dgda.gov.bd
Joined the WHO program Not yet a member of the WHO Programme for International Drug
Monitoring
Significant events 2008 reports of poor-quality generic miltefosine for visceral
leishmaniasis that contained no active pharmaceutical ingredient
E2B compliance Not applicable
Medical terminology used Not applicable
Type of reports in PV database None
Total number of ICSRs in the database None
Quantitative methods used in Not applicable
signal generation
Newsletter or bulletin published Not regularly published
annexes 115
Cambodia
GDP per capita (USD)* $900, 2011
Market size: pharmaceuticals (USD, 2011)† 178 million
Number of medicines registered (2011)‡ 10,000 (est.)
Total expenditure on healthcare per capita (USD, 2010) § $29
Total pharmaceutical (TPE) expenditure per capita (USD, 2006) || $9.3, 2006
Public expenditure on pharmaceuticals per capita (USD, 2006) || $1.3, 2006
TPE as % total expenditure on healthcare per capita (2006)|| 21%, 2006
Health workforce per 10,000 population# 10.8
Financing mechanisms for pharmaceuticals# Public (14%), Private/Other (86%)
Medicines Policy
Policy, laws, and regulations National Medicine Policy (1996)
National Medicine Policy (2010)†
Law on the Management of Pharmaceuticals (1996)††
Law on the Management of Pharmaceuticals (amended 2007)
Pharmaceutical Sector Strategic Plan 2005-2010
Patent provisions (main)** The Constitution of the Kingdom of Cambodia (1999)
Law on the Management of Pharmaceuticals (1996, 2007)
Law on Patents, Utility Models and Industrial Designs (2003)
Law on Copyright and Related Rights (2003)
Law concerning Marks, Trade Names and Acts of Unfair Competition of
the Kingdom of Cambodia (2002)
WTO TRIPS Agreement (1994)
Pharmaceutical Production†
Total no. of pharmaceutical manufacturing plants 8
No. of pharmaceutical manufacturing plants:
pharmaceutical active ingredients 0
finished pharmaceutical dosage forms 8
packaging finished pharmaceutical dosage forms 8
No. of research-based pharmaceutical industries 0
No. of generic pharmaceutical (including branded generics) manufacturers 8
No. of nationally owned pharmaceutical industries (public and private) 8
* World Bank Database , accessed date 30/08/2012

† Business Monitor International Cambodia Pharmaceuticals and Healthcare Report 2012
‡ Cambodia MOH, DDF
§ Global Health Expenditure Database
|| World Medicines Situation
** World Intellectual Property Organization
†† National Assembly of Cambodia

Policy, laws, and regulations National medicines policy (1996 and 2010)
National pharmaceutical law
Pharmaceutical Strategic Plan 2008-2015
ADR Monitoring and related Matters guidelines (2012)
Name of regulatory authority/website DDF: www.ddfcambodia.com
Mandate of regulatory authority Registration, licensing and import control, inspection, quality control,
PV, control of promotion, control of clinical trials
How products get into the market Registration by DDF, list of registered products available (10,171)
Joined the WHO program Official member, 2012
Significant events Chloramphenicol injection and capsule withdrawn from National
Essential Drug List
E2B compliance Through VigiFlow (E2B-compliant, web- based portal)
Medical terminology used WHO-ART
Type of reports in PV database Spontaneous reports
Total # of ICSRs in the database > 137 total, 83 in 2011
Quantitative methods used in signal generation The Bayesian Confidence Propagation Neural
Network (BCPNN)
Newsletter or bulletin published Yes, but not regularly published as planned (funding constraint)
annexes 117
Nepal
Gross domestic product per capita (USD, 2011)* $619 per capita
Gross domestic product (USD, 2011)* $18.9 billion
Market size: pharmaceuticals (USD, 2009)† $187.64 million
Market size: medical devices (USD, 2009) Included in above
Number of medicines registered‡ 10,316 per WHO
Total expenditure on healthcare per capita (USD, 2010)§ $29, USD
Total pharmaceutical expenditure per capita (USD, 2006)§ $4.7
TPE as % total expenditure on healthcare per capita§ 16%
Public expenditure on pharmaceuticals per capita (USD, 2011)‡ $0.9
Health workforce per 10,000 population (2010)|| 16.1
Financing mechanisms for pharmaceuticals‡ Public (19%), Private (81%)
Medicines Policy
Policy, laws, and regulations Drug Act 2035 (1978)#
National Drug Policy, 1995#
National Medicines Policy (draft)**
Drug Investigation and Inspection Rules, 2040 (1983)
Drug Registration Regulation, 2038 (1981)
Drug Standards Regulation, 2043 (1981)
Regulation on Constitution of Drug Consultative Council and Drug
Advisory Committee, 2037 (1970)
Patent provisionsf The Interim Constitution of Nepal 2063 (2007);
The Patent, Design and Trade Mark Act, 2022 (1965); Copyright Act, 2059
(2002); Copyright Rules (2004);
Pharmaceutical Production††
Total no. of pharmaceutical manufacturing plants 45
pharmaceutical active ingredients None
finished pharmaceutical dosage forms 45
No. of research-based pharmaceutical industries None
No. of generic pharmaceutical (including branded generics) manufacturers None

† Nepal National Health Account (2006 – 2009)
‡ WHO Nepal Pharmaceutical Country Profile
§ WHO National Health Accounts Database
|| WHO World Medicines Situation
# WHO Nepal Pharmaceutical Country Profile
** World Intellectual Property Organization: Nepal
††Nepal Department of Drug Administration

Policy, laws, and regulations Drug Act 2035 (1978)

National Drug Policy, 1995
National Medicines Policy (draft)
Name of regulatory authority / website Ministry of Health and Population, Department of Drug
Administration (DDA)
www.dda.gov.np
Mandate of regulatory authority Manufacturing, export/import, sales, distribution, storage
How products get into the market Registration by DDA for import, production, sales, distribution
Joined the WHO program Official member (2006)
Significant events Not applicable
E2B compliance Through VigiFlow (E2B-compliant, web-based
portal)
Type of reports in PV database Spontaneous reports from 6 regional PV centers; AEFI reports
Total number of ICSRs in the database 411 through 2012 (35 in 2011)
Quantitative methods used in signal generation WHO Drug Database quarterly scan using BCPNN
Newsletter or bulletin published Drug Bulletin of Nepal, Three newsletters per year
annexes 119
The Philippines
Population (million, 2011)* 94.9 million
Gross domestic product per capita (USD, 2011)* 2,370
Market size: pharmaceuticals (USD, 2011)† 2.91 billion
Number of medicines registered (2012)‡ 32,069
Total expenditure on healthcare per capita (USD, 2009)§ 77
Total pharmaceutical expenditure per capita (USD, 2006)|| 21.3
Public expenditure on pharmaceuticals per capita (USD, 2006)|| 2.1
TPE as percentage of total expenditure on healthcare per capita 28%
Health workforce per 10,000 population (2011)# 10.2 physicians; 53.1 nursing and midwifery personnel;
5.4 licensed pharmacists; 11.0 pharmaceutical personnel
Financing for pharmaceuticals Public (10%), Public/Other (90%)
Medicines Policy
Policy, laws, and regulations Foods, Drugs and Devices, and Cosmetics Act, 19875
The Generics Act, 19886
Universally Accessible Cheaper and Quality Medicines Act, 20087
Patent provisions** Constitution of the Republic of the Philippines, 1987
Intellectual Property Code of the Philippines, 19978
Universally Accessible Cheaper and Quality Medicines Act, 20087
Pharmaceutical Production Status†† (2012)
Pharmaceutical manufacturing plants 301
No. of pharmaceutical manufacturing plants 301
producing pharmaceutical active ingredients (2011) 0
producing finished pharmaceutical dosage forms 93
No. of nationally owned pharmaceutical industries (public and private)‡‡ 4

† Business Monitor International Philippines Pharmaceuticals and Healthcare Report 2013
‡ Directorate General of Drug Administration
§ WHO National Health Account Database, 2010
|| WHO World Medicines Situation 2011 Annex

** WIPRO
†† FDA database as of June 2012
‡‡ Includes only data from government-owned – Philippines Institute of Traditional and Alternative Health Care (PITAHC)
5 Executive Order No. 175
6 Republic Act No. 6675

Policy, laws, and regulations Food, Drugs, Devices and Cosmetics Act , 1987
National Policy and Program on Pharmacovigilance, 2011
Philippine Medicines Policy –Draft
Generics Act of 1988
Universally Cheaper and Quality Drug Act of 2008
Name of regulatory authority / website Food and Drug Administration Philippines, www.fda.gov.ph
PV, control of promotion and advertising, control of clinical trials
How products get into the market Registration by FDA Philippines, list of registered drugs: www.fda.
gov.ph/registered-drugs
Joined the WHO program Official (1995)
Significant events Not applicable
E2B compliance Through VigiFlow (E2B-compliant, web- based
portal)
Type of reports in PV database Spontaneous reports, AEFI reports, reports from industry
Total number of ICSRs in the database 13,390 (2006 – 2011), 3,351 (2011)
Quantitative methods used in signal generation BCPNN
Newsletter or bulletin published No, medicine safety alerts published on website
annexes 121
Thailand
Gross domestic product (USD, 2011)* 4,972 per capita
Market size: pharmaceuticals (USD, 2011)† 4 billion
Market size: medical devices (USD, 2011)† 1.11 billion
Number of medicines registered (item, 2011)‡ 24,087 human medicines; 2410 medical devices;
60 narcotics; 28 controlled substances
Total expenditure on healthcare per capita (USD, 2010)* 179
Total pharmaceutical expenditure per capita (USD, 2011)† 70
TPE as % of total healthcare expenditure per capita (2010) 39.1%
Public expenditure on pharmaceuticals per capita (USD, 2011)† 42.5
Health workforce per 10,000 population (2011)§ Physicians: 3.0; Nurses/midwives: 15.2;
Pharmaceutical personnel: 1.2; Dentistry personnel:
0.7; Environmental and public health workers: 0.4
Financing mechanisms for pharmaceuticals Public (88%),
Private/Other (12%)*
Medicines Policy
Legal Provision for Medicines Legislation‡ Drug Act 1967
Psychotropic Substances Act 1975
Narcotics Act 1979
Existence of National Medicines Policy|| National Drug Policy A.D.2011 and
National Drug System Development Strategy A.D.2012-2016
Patent provisions# The Permanent Constitution of the Kingdom of Thailand (2007)
Thai Patent Act B.E. 2522 (1979), as amended by
Patent Act (No. 2) B.E. 2535 (1992) and the Patent Act (No. 3) B.E. 2542
(1999)
WHO TRIPS Agreement (1994)
Pharmaceutical Production Status‡ (2011)
Total no. of pharmaceutical manufacturing plants 724 (163 modern medicine,
561 traditional medicine)
producing pharmaceutical active ingredients 6
producing finished pharmaceutical dosage forms 721
† Business Monitor International Thailand Pharmaceuticals and Healthcare Report 2013
‡ Thai FDA, 2011
§ WHO World Health Statistics 2012, Accessed 30/08/2012
|| WIPO, Accessed 27/08/2012
# WHO World Health Statistics 2012, Accessed 30/08/2012

Policy, laws, and regulations Drug Act (1967)

National Drug Policy (2011) Strategy on National Drug System
Development 2012-2016
Name of regulatory authority/website Thai Food and Drug Administration
www.fda.moph.go.th
PV, control of promotion, control of clinical trials
How products get into the market Registration by Thai FDA, List of registered drugs vaccines:
drug.fda.moph.go.th/ zone_service/ser020.asp
Joined the WHO program Official (1984)
Significant events Hepatic injury associated with Cassia siamea (leaf) and increasing
the frequency of pure read cell anemia associated with erythropoietin
(detected from Thai FDA database)
E2B compliance INTDIS format
Medical terminology used WHO-ART for ADR terminology
ATC code for medicine
ICD-10 for indication
Type of reports in PV database Spontaneous reports, AEFI reports, active surveillance reports,
product quality reports, PSURs, reports from PHPs
Total number of ICSRs in the database 57573 in 2011
Quantitative methods used in signal generation Reporting Odd Ratio (ROR), implemented since 2006
Newsletter or bulletin published Medicinal and Health Product Bulletin (quarterly) and HPVC
Newsletter (occasionally for safety and information alerts)
annexes 123
Annex D. Assessment Method
Literature Search
In each of the countries assessed, a literature search was conducted to identify articles published in peer-reviewed journals
with methods, outcomes, or both relevant to PV and medicine safety. The following search terms were used:
“OR” OR “adverse effect” OR “side effect monitoring” OR “drug safety” OR “drug toxicity” OR “adverse events following
immunization” OR “AEFI” OR “pharmacovigilance” OR “pharmacoepidemiology” OR “medicine safety” OR “active
surveillance study” OR “adverse reaction study” OR “post marketing surveillance” OR “product surveillance”) AND
“[country].”
Only studies published after 1997 were included. Titles and abstracts were reviewed for relevance, and articles not reporting
effectiveness, efficacy or safety (including adverse event reporting) of a medicine or pharmacologic product were removed.
Additional information was obtained from:
§§ National medicines policy

§§ National medicines legislation
§§ Regulatory systems, governance, and policy
§§ National lists of registered products and the list of licensed pharmaceutical premises
§§ Organization charts
§§ Annual center report and activity reports
§§ Relevant committee meeting minutes
§§ Reports on pharmaceutical market size and industry medicine safety activities
§§ Reports of recent safety events and recent reviews
Site Selection
Several sites were chosen based on various criteria (see “Study Methods” section within report for more detailed
information). The table below summarizes some of the sites that were chosen in each of the individual countries.
Selected Sites Visited Across Studied Countries

Bangladesh Cambodia Nepal Philippines Thailand Total
National 6 9 8 9 10 42
Public Health Programs 4 3 4 5 7 23
Health Facilities 23 11 17 23 12 86
Pharmacies 10 14 15 32 3 74
Consumer Groups 1 2 3 3 1 10
Pharmaceutical Industries 9 3 4 9 12 37
Academia 3 2 7 7 3 22
Indicator-Based Pharmacovigilance Assessment Tool (IPAT)

An analysis of each countries’ PV system was determined using the indicator-based pharmacovigilance assessment tool
(IPAT) developed by the USAID-funded Strengthening Pharmaceutical Systems (SPS) program. More specific information
about the indicators included in IPAT can be found here: http://pdf.usaid.gov/pdf_docs/PNADS167.pdf

Annex E. PV Topics in Curriculum
Modules Sessions Contents

Fundamental Topics
Overview of national §§ National medicines policy
medicine policy and §§ Legislations and regulations related to medicines and health products
regulatory system §§ PV as described in the medicine policy in the legislations
§§ History of medicine regulation
History and overview
§§ History of PV
1. Regulatory PV of PV
§§ Evaluating safety throughout the life cycle of a medicine
§§ National PV guidelines
Overview of national §§ Roles and responsibilities of stakeholders in PV
guidelines for medicine
safety surveillance §§ ADR notification system
§§ List of tools used in medicine safety
Definitions and §§ Definitions in PV
classification of §§ Classifications and types of ADR, medication error, and poor product quality
adverse events §§ Adverse events predisposing factors
§§ Spontaneous reporting
§§ Keys areas of the adverse event notification form
Adverse event reporting
2. Risk identification §§ Strengths and limitations of spontaneous reporting
§§ Sources of spontaneous reports
§§ Causation and hypothesis generation
Causality assessment §§ Causality assessment
and signal generation §§ Signals, their sources and characteristics
§§ Strengths /weaknesses of methods used to identify safety signals
§§ Active surveillance method
§§ Active sentinel surveillance system
§§ Drug event monitoring
Active surveillance
§§ Registries
3. Risk evaluation §§ Record linkage studies
§§ Descriptive studies (drug utilization studies)
§§ Cohort studies
Comparative
§§ Case-control studies
observational studies
§§ Targeted clinical investigations
§§ Types and causes of medication errors
Medication error
§§ Sentinel event reporting
and patient safety
§§ Strategies for reducing medication error
§§ Sources of information on medicines
4. Patient safety, risk §§ Hierarchy of evidence
Medicine information
management, and
and risk communication §§ Use of information technology in risk communication
communication
§§ Systems and strategies for providing information on medicines
§§ Principles of risk management
Risk management
§§ Scope and objectives of risk management
strategies
§§ Risk management strategies
annexes 125
Modules Sessions Contents
Electives: PV in Public Health Programs
§§ Medicines used in the national guidelines for the management of
opportunistic infections and HIV and AIDS
ARVs and opportunistic §§ Burden of ARV-related morbidity and mortality
5 (a). HIV and AIDS
infection medicines
§§ Measures to reduce ARV-related morbidity
§§ Improving adverse event reporting in antiretroviral therapy program
§§ Medicines used in the national guidelines for the management of TB
§§ Burden of anti-TB medicines adverse events
5 (b). TB Anti-TB medicines
§§ Measures to reduce adverse events related to anti-TB medicines
§§ Improving adverse event reporting in the national TB program
§§ Medicines used in the national guidelines for the management of malaria
§§ Burden of antimalaria medicines adverse events
5 (c). Malaria Antimalaria medicines
§§ Measures to reduce adverse events related to malaria medicines
§§ Improving adverse event reporting in the national malaria program
§§ Vaccines used in the national immunization guidelines
§§ Burden and challenges of monitoring adverse events in pediatrics, vaccines,
5 (d). PV in pediatrics, Vaccines and mother and and family planning health products
vaccine/ immunization child health products §§ Adverse events following immunization and measures to reduce vaccine-
related adverse events
§§ Improving adverse event reporting in the national malaria program

Annex F. Thailand Health Product Adverse Event Report Form
L E
P
A M
S
annexes 127
Annex G. Glossary
Active surveillance: The collection of case safety information as a continuous, preorganized
process. It includes a wide range of active approaches to detect and evaluate risks, such as
cohort event monitoring, registries, sentinel sites, epidemiological studies (case control study,
cohort study, cross sectional study), and phase 4 clinical trials.
Adverse event: Any untoward medical occurrence in a patient or clinical investigation

subject administered a pharmaceutical product and which does not necessarily have a causal
relationship with this treatment. It may be due to poor product quality, medication error, or
known or unknown pharmacological properties.
Adverse drug reaction: A response to a drug which is noxious and unintended and which
occurs at doses normally used in humans for the prophylaxis, diagnosis, or therapy of disease,
or for the modification of physiological function.
Bayesian Confidence Propagation Neural Network: Automated data mining program

used by the Uppsala Monitoring Centre. This produces information component values for
drug-event combinations. These can be plotted as graphs over time to examine any trend. A
positive signal will have information component values that become more significant over
time as more cases are included.
Benefit/risk analysis: Comparing the therapeutic benefits from having a medical

intervention to the risk of causing adverse effects
Case control study: Study that identifies a group of persons who experienced the
unintended drug effect of interest (cases) and a suitable comparison group of people without
the unintended effect (control). The relationship of a drug to the drug event is examined by
comparing the cases and control with regards to how frequently the drug is present.
Causality assessment: The evaluation of the likelihood that a medicine was the causative
agent of an observed adverse event. Causality assessment is usually made according to
established algorithms.
Clinical trial: A systematic study on pharmaceutical products in human subjects (including

patients and other volunteers) to discover or verify the effects of or identify any adverse
reaction to investigational products, or to study the absorption, distribution, metabolism, and
excretion of the products with the objective of ascertaining their efficacy and safety.
Cohort event monitoring: A surveillance method that requests prescribers to report all
observed events, regardless of whether or not they are suspected ADRs, for identified patients
receiving a specific drug; also called prescription event monitoring.
Counterfeit medicines: Products that are deliberately and fraudulently mislabeled with
respect to identity and/or source.
Drug use study/Medicine utilization review: A program to review medicine prescribing,

dispensing, or patient use of medicines.
Effectiveness/Real-life effectiveness: The outcome or result of applying a particular drug,

medical treatment, or service in a particular group of patients or the performance of a
product under real-life conditions.
Efficacy: The scientifically demonstrated ability of a therapeutic agent or procedure to

consistently affect a specific predictable desirable health intervention within a given
population under defined conditions.

Falsified medicines/Fake medicines: A medicine that falsely represents a product’s proper
active ingredient, source, or both
High-risk medicines: Those medicines that have a heightened risk of causing significant or
catastrophic harm when used in error.
Individual case safety report: A report that contains information describing a suspected
ADR related to the administration of one or more medicinal products to an individual
patient.
Market authorization: An official document issued by the competent drug regulatory

authority for the purpose of marketing or free distribution of a product after a satisfactory
evaluation for safety, efficacy and quality.
Medication errors: Any preventable event that may cause or lead to inappropriate
medication use or patient harm while medication is in the control of the healthcare
professional, patient, or consumer.
Medical Dictionary for Regulatory Activities: A medical terminology used to classify

adverse event information associated with the use of biopharmaceuticals and other medical
products (e.g., medical devices and vaccines). Coding these data to a standard set of
MedDRA terms allows health authorities and the biopharmaceutical industry to more readily
exchange and analyze data related to the safe use of medical products.
Pharmacoepidemiology: Study of the use and effects of drugs in large populations.
Pharmacovigilance (PV)/medicine safety: The science and activities relating to the

detection, assessment, understanding, and prevention of adverse effects or any other possible
drug-related problems. The aims of PV are early detection of hitherto unknown adverse
reactions and interactions, detect increases in frequency of known adverse reactions,
identify risk factors and possible mechanisms underlying adverse reactions, and estimate
quantitative aspects of benefit/risk analysis, and disseminate information needed to improve
drug prescribing and regulation. The scope of PV includes adverse reactions, medication use
errors, product quality complaints, and lack of efficacy.
Pharmacovigilance system: PV systems that include all entities and resources that protect
the public from medicines-related harm, whether in personal healthcare or public health
services. The system addresses the need for both active and passive approaches to identify
and assess medicines-related problems, effective mechanisms to communicate medicine
safety information to healthcare professionals and the public, collaboration among a wide
range of partners and organizations, and incorporation of PV activities at all levels of the
health system.
Post-marketing surveillance: The systematic process of monitoring the use of medical

products after a product has been approved. PV is part of post-market surveillance.
Product quality survey: A study that has sampled and tested the quality of medicines
according to a standard procedure of quality surveillance.
Product life-cycle: Period from pre-market animal and human safety testing to widespread
clinical use beyond original indications
annexes 129
Quality: The suitability of either a drug substance or drug product for its intended use.
This term includes such attributes as the identity, strength, and purity (from ICH Q6A
Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug
Products: Chemical Substances)
Quality assurance: An organized arrangement (processes and systems) of all elements

that influence the quality of the product. It involves inspection of compliance with Good
Manufacturing Practices, assessment of documentation on product quality submitted by the
manufacturer, sampling and testing of medicines from the market or different entry points,
and systematic evaluation of reported quality problems through the PV system.
Registries: A list of patients presenting with the same characteristic(s). This characteristic
can be pregnancy (pregnancy registry), a disease (disease registry), or a specific exposure
(drug registry).
Risk management/risk management plans: A set of activities designed to identify,

characterize, prevent, or minimize risks related to the medicine; to assess the effectiveness of
those interventions; and to communicate those risks to patients and healthcare providers.
Safe: Free from unacceptable risk
Sentinel sites: The selected sites that can provide complete and accurate information on
reported adverse events, such as data from specific patient subgroups.
Serious adverse events: Any untoward medical occurrence that at any dose results in
death; is life-threatening; requires inpatient hospitalization or prolongation of existing
hospitalization; results in persistent or significant disability/incapacity; or is a congenital
anomaly/birth defect.
Signal: Reported information on a possible causal relationship between an adverse event and
a drug, the relationship being unknown or incompletely documented previously that may be a
new adverse effect or a change in the character or frequency of an ADR that is already known.
Spontaneous reporting: Unsolicited communication by healthcare professionals or

consumers that describes one or more suspected adverse events in a patient who was given
one or more medicinal products and that does not derive from a study or any organized data
collection scheme.
Stringent regulatory authorities: Members, observers, or associates of the International

Conference on Harmonization of Technical Requirements for Registration of
Pharmaceuticals for Human Use.
Substandard medicines: Products whose composition and ingredients do not meet the
correct scientific specifications and that are consequently ineffective and often dangerous to
the patient.
Treatment failure: Unexpected failure of a drug to produce the intended effect as

determined by previous scientific investigation.
VigiBase: WHO’s International Adverse Drug Reaction Database.
VigiFlow: A sophisticated case report management system created by the Uppsala

Monitoring Centre for the submission of spontaneous ADR reports.
WHO-ART: WHO terminology for coding clinical information in relation to drug therapy.

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Index
A Regional Harmonization Steering regional harmonization initiatives, 33

Academic institutions, 97, 98, 100 Committee (RHSC), 30, 37 regulatory frameworks, 14
Action Taken Reports, 108 Audits and inspections, 95 regulatory registers, 14
Active surveillance, 128 Australia, 70 reporting of adverse events, 15, 53, 84
Adverse drug events (ADEs). See Adverse risk assessment and evaluation, 55, 56, 112
events (AEs) B risk management and communication, 60,
Adverse drug reactions (ADRs) Bangladesh 65, 112–113
costs of, 28 civil society, 97 signal generation and data management,
definition of, 128 consumer groups, 99 52, 53, 111
prevalence of, 28 data management, 51 sites visited, 124
reporting, 53, 55, 71–73, 83, 84, 91 data mining methods, 51, 52 unregistered medicines, 15, 57
reporting forms, 22, 52–53, 91 Directorate General of Drug WHO International Drug Monitoring
Adverse Drug Reaction’s Community of Administration (DGDA), 7 Programme membership, 47
Pharmacy Practice (ADCoPT) (Thailand), funding for PV activities, 45 WHO-UMC membership, 29
55 governance structures, 14 Barcoding, 74
Adverse events (AEs) gross domestic product (GDP), 20 Baxter, 27
definition of, 128 health facilities, 81, 84, 86, 87 Bayesian Confidence Propagation Neural
reporting, 14, 15, 18, 88, 95 immunization program, 15 Network, 128
reporting forms, 14, 53, 91, 127 medical products, 39, 57, 58, 61, 63 Benefit/risk analysis, 128
serious, 130 medicine safety regulatory actions, 59 Bhutan, 29
Advertisements, 42 medicines policy, 114 Bill & Melinda Gates Foundation, 103
Afghanistan, 29 Ministry of Health and Family Welfare Brighton Collaboration, 104
AIDS, 21 (MOHFW), 7 Brunei Darussalam, 29
Antiretroviral Pregnancy Exposure Registry, national guidelines/standard operating
79 procedures, 46 C
ASEAN Economic Community (AEC) National Pharmacovigilance Center, 7, 45 Cambodia
Blueprint, 32 National Pharmacovigilance Program, 7, civil society, 97
ASEAN Free Trade Area (AFTA), 32 65, 115 consumer groups, 99
Asia pharmaceutical industry, 41, 92, 93, 94, data management, 51
challenges for PV systems, 34–35 114 data mining methods, 51, 52
comparative analysis of country studies, pharmaceutical market, 20, 21, 114 Department of Drugs and Food, 64
26 pharmaceutical production status, 114 drug trafficking, 27
comparative analysis of PV systems, 37 pharmaceutical profile, 114 funding for PV activities, 45
country assessments, 25–26 pharmacies, 84, 87 gross domestic product (GDP), 20
country profiles, 114–123 pharmacovigilance governance, 40, 110 health facilities, 81, 84, 87
pharmaceutical market, 13, 19–20 pharmacovigilance performance, 101, 102 legislation, 14, 40, 41
pharmacovigilance in, 30, 31, 101–102 pharmacovigilance policy, law, and medical products, 57, 58
regional harmonization initiatives, 30–33 regulation, 43, 110 medication mishaps, 108
See also specific countries pharmacovigilance profile, 110–113 medicine information offices, 57
Asia Pacific Economic Collaboration pharmacovigilance system, structure, medicine safety regulatory actions, 59
(APEC), 30–32, 33 and stakeholder coordination, 49, 98, Medicines Safety Advisory Committee, 14
Asian Harmonization Working Party 110–111 national guidelines, 14, 46, 97
(AHWP), 30–32, 33, 69 population, 19, 20 National Medicine Policy, 7, 116
Association of Southeast Asian Nations product register, 39 pharmaceutical industry, 89, 93, 94
(ASEAN) professional associations, 99 pharmaceutical legislation, 41
Pharmaceutical Product Working Group, public communication activities, 58, 59 pharmaceutical market, 20, 21
32, 33, 68 public health programs, 76, 77, 78 pharmaceutical production, 116
post-marketing alert (PMA) system, 15, quality assurance, 61, 63 pharmaceutical profile, 116
32, 58, 104 quality control lab services, 46 pharmacies, 84, 85
index 137
pharmacovigilance, 102 risk management and communication, 98 Drug safety. See Safety
pharmacovigilance centers, 45 signal generation and data management, Drug trafficking, 27
pharmacovigilance governance, 39–40, 98 Drug use studies, 128
110 systems, structures, and stakeholder Drugs for Neglected Diseases Initiative, 104
pharmacovigilance profile, 110–113, 116 coordination, 97, 98 Drugs@FDA, 30
pharmacovigilance requirements, 40 Clinical research organizations (CROs) DTCs. See Drug and Therapeutic
pharmacovigilance system, 7–8, 16, 49, 65, availability of forms, 91 Committees
110–111 medicine/device safety information
policy, law, and regulation, 43, 110 requests, 92 E
population, 19, 20 PV capacity, 92, 94 Effectiveness, 128
product quality assurance, 61, 63 risk assessment and evaluation, 91, 92 Efficacy, 128
product register, 39 risk mitigation plans for high-risk EudraVigilance, 72
professional associations, 99 medicines, 92 European Commission, 103
public communication activities, 58, 59 SOPs for PV and medicine safety, 90 European Medicines Agency (EMA), 30, 31,
public health programs, 15, 78 staff training, 90 72, 73
quality control lab services, 46 systems, structures, and stakeholder European Network of Centres for
regional harmonization initiatives, 32, 33 coordination, 89–90 Pharmacoepidemiology and
registered products, 32 Clinical trials, 28–29, 128 Pharmacovigilance, 80
reporting of ADRs, 53, 84 Code of Federal Regulations (US), 30 European Public Assessment Report
risk assessment and evaluation, 55, 56, 112 Cohort event monitoring, 128 (EPAR), 30
risk management and communication, Collaboration, international, 29–30 European Union (EU), 30, 31, 71
14–15, 57–58, 59, 60, 112–113 Common Technical Document (CTD), 30,
risk mitigation plans for high-risk 68 F
medicines, 57–58 Communication. See Risk management and Falsified and substandard products
signal generation and data management, communication confronting, 17, 73–74
52, 53, 111 Communication technologies, 47, 50, 90 definition of, 129
sites visited, 124 Community pharmacies, 86, 87, 88 rapid alert system, 74
unregistered medicines, 14–15, 57, 64 Compounding manufacturers, 109 Federal Food, Drug and Cosmetic Act (US),
WHO International Drug Monitoring Consumer groups, 97, 98, 99 27, 108
Programme membership, 47 Consumer reporting, 100 Financing institutions, 103
WHO-UMC membership, 29 Continuing education programs, 97 Food and Drug Administration (FDA) (US),
Case control studies, 128 Council for International Organizations of 13, 28, 31, 71
Causality assessment, 128 Medical Sciences (CIOMS), 22, 23, 104 Center for Biologics Evaluation and
Cell phones, 72 Counterfeit medicines, 128 Research, 104
Center for Biologics Evaluation and Country assessments, 25–26 regulatory reforms, 108, 109
Research (FDA), 104 Food and Drug Administration
Central Drugs Standard Control D Amendments Act (FDAAA) (US), 30, 108
Organization (CDSCO), 28, 108 Data management France, 71, 108
China data from patient files, 88 Funding
drug safety system, 31 in health facilities, 83, 84 grants, 45, 46, 80
drug trafficking, 27–28 online, 72 improving, 17, 70–71, 79
medication mishaps, 108 in public health programs, 75–76, 77
pharmaceutical market, 13, 19, 21 for reports, 72 G
poor quality products, 34 strengthening, 17 GAVI alliance, 103
State Food and Drug Administration systems for coordination and collation of GCG. See Global Cooperation Group
(SFDA), 27, 28, 73 data, 51–52 Generic medicines, 13
WHO-UMC membership, 29 See also Signal generation and data Germany, 71
China Food and Drug Administration management Global Cooperation Group (GCG), 22, 23
(CFDA), 27, 28, 73 Data mining methods, 51, 52 Global Fund to Fight AIDS, Tuberculosis
CIOMS. See Council for International Documents. See Reporting forms and Malaria (Global Fund), 45, 46, 80, 103
Organizations of Medical Sciences Donation programs, 17, 80 Global Harmonization Task Force (GHTF),
Civil society, 97–100 Drug and Therapeutic Committees (DTCs), 22, 23, 95
options for improving PV, 100 58, 88 Global Individual Case Safety Reports
pharmacovigilance capacity, 98 Drug information centers, 47 database (WHO), 34
policy, laws, and regulation, 97 Drug Regulatory Authority (Pakistan), 28, Global initiatives, 103–104
recommendations for, 18 108 Global Regulatory Utilization of Vaccine
risk assessment and evaluation, 98 Drug relief funds, 71 Safety Surveillance initiative, 104

Good distribution practices (GDP) Institute of Medicine (IOM) (US), 29, 70 medicine/device safety information
guidelines, 61 International collaboration, 29–30 requests, 92
Guidelines International Conference on Harmonization pharmacovigilance capacity, 92, 94
comprehensive, 71 of Technical Requirements for Registration policy, law, and regulation, 89
national, 14, 46, 97 of Pharmaceuticals for Human Use (ICH), quality control units, 90
for safety, 22 22, 23, 30, 72, 104 recommendations for, 18
International Drug Monitoring Programme risk assessment and evaluation, 91, 92
H (WHO), 14, 22, 47, 50 SOPs for PV and medicine safety, 90
Harmonization initiatives, 30–33 International Epidemiologic Database to staff training, 90
Health facilities Evaluate HIV/AIDS, 80 systems, structures, and stakeholder
definition of, 81 International institutions, 104 coordination, 89–90
options for improving PV, 88 International Medical Device Regulators Medical devices, 32
pharmacovigilance capacity, 86, 87 Forum (IMDRF), 22, 23 adverse event reporting, 95
policies, laws, and regulation of, 81 International Pharmaceutical Federation, regulation and vigilance of, 18, 95
recommendations and options for, 17–18 104 Medical Devices Post Market Surveillance:
reporting AEs, 84 International regulations, 16, 67–68 Global Guidance for Adverse Event
risk assessment and evaluation, 84 International Society of Pharmacovigilance, Reporting for Medical Devices (Global
risk management and communication, 104 Harmonization Task Force), 22, 95
85–86 International Standards Organization (ISO), Medical Dictionary for Regulatory Activities
signal generation and data management, 22, 69 (MedDRA), 30, 129
83 Medical products, 57, 58
systems, structure, stakeholder J falsified and substandard, 17, 73–74, 129
coordination, 81–82 Japan life-cycle of, 129
Health Level Seven International (HL7), 22 drug relief funds, 71 quality assurance, 41, 63
Health Product Vigilance Center (HPVC) drug safety system, 30, 31 quality surveillance, 61–64
(Thailand), 45, 69, 72 Early Post-Marketing Phase Vigilance, 73 Medication errors, 129
Health Sciences Authority (Singapore), 69 pharmaceutical market, 13, 21 Medication mishaps, 27–33, 108–109
Health workers, 17, 88 WHO-UMC membership, 29 Medicine information offices, 57
HIV and AIDS, 21, 78, 79–80, 126 Medicine safety, 129
HIV and AIDS programs, 78, 79–80 K advisory committees for, 14, 47
Korea, Dem. Rep, 29, 30, 72 bulletins, 14–15
I information processes, 57
ICH E2B format, 72 L information requests, 57–60, 92
IMDRF. See International Medical Device Laos, 27, 29, 103, 108 reference materials, 50
Regulators Forum Le Monde, 108 regulatory actions, 59
In-service training, 88 Legislation, 14, 97 staff training, 90
India medicines, 40 statements on PV or medicines safety, 40
drug regulation, 28 pharmaceutical, 41, 42–43, 89 Medicine safety alerts, 92
drug safety system, 31 product quality assurance, 41 Medicine safety bulletins, 57, 85
medication mishaps, 108, 109 promotion and advertisement, 42 Medicine utilization reviews, 128
pharmaceutical market, 19 public health programs, 75 Medicines
poor quality products, 34 service delivery, 81 high-risk, 57–58, 63–64, 129
regulatory reforms, 108, 109 Literature search, 124 legislation of, 40
WHO-UMC membership, 29 regulation of, 27–33
Indicator-based pharmacovigilance M tolerability of, 17, 79
assessment tool (IPAT), 124 Malaria, 21, 126 unregistered, 57, 64
Individual case safety reports (ICSRs), 22, Malaysia, 29 Medicines and Healthcare Products
26, 72, 129 Management Sciences for Health, 104 Regulatory Agency (UK), 68–69, 70
Indonesia, 29, 103, 108 Mandatory reporting, 40 Medicines for Malaria Venture, 104
Information collection, 17, 79–80 Market authorization, 129 Medicines information service, 47
Information services, 47, 90 Market authorization holders, 40 Medicines policy. See specific countries
Information sharing, 16, 68–69 Médecins Sans Frontières, 104 Ministry of Health and Family Welfare
Information technologies, 72 Medical device companies (India), 108
Inspection Co-Operation Scheme Procedure availability of forms, 91 Mongolia, 29
for Handling Rapid Alerts and Recalls communication technologies, 90 Monitoring Medicines program, 103
Arising from Quality Defects (PIC/S core reference materials, 90 Myanmar, 27, 29, 108
2011), 68–69 funding for PV, 90
index 139
N reporting of ADRs, 53 risk assessment and evaluation, 91, 92
National Agency for the Safety of Medicines risk assessment and evaluation, 55, 56, 112 risk management and communication, 92
and Health Products (MSNA) (France), risk management and communication, 59, risk management plans, 95
108 60, 112–113 signal generation and data management,
National guidelines, 14, 46, 98 signal generation and data management, 91
National Health Security Office (NHSO) 52, 53, 111 systems, structures, and stakeholder
(Thailand), 55 sites visited, 124 coordination, 89–90
National Institutes of Health (NIH) (US), unregistered medicines, 57 Pharmaceutical market, 13, 19–20
79–80 WHO International Drug Monitoring Pharmaceutical product market
National Medicine Policy (Cambodia), 7 Programme membership, 47 authorization holders, 40
National Medicines Policy (NMP), 40 WHO-UMC membership, 29 Pharmaceutical Product Working Group
National Pharmacovigilance Center New England Compounding Center (PPWG) (ASEAN), 32, 33
(Bangladesh), 7 (NECC), 109 Pharmaceuticals Newsletter (WHO), 62
National Pharmacovigilance Program Niger, 108 Pharmacies
(Bangladesh), 7 Nigeria, 108 ADR reporting forms, 83
National Policy and Program on ADR reports, 84
Pharmacovigilance (Philippines), 40, 67 P community, 86, 87, 88
National regulatory authorities (NRAs), Pakistan, 28, 29, 108 consumer reporting forms, 83
105 Pan-Asian Clinical Research Association, options for improving PV, 88
National standard operating procedures, 46 104 pharmacovigilance activities, 82
Nepal Panama, 108 pharmacovigilance capacity, 86, 87
cell phones, 72 Patient files, 88 private, 82, 84, 85–86, 87
consumer groups, 99 “PDP Access Group” (Product Development risk management and communication,
data management, 51 Partnership Access Group), 104 85–86
data mining methods, 51, 52 Pediatrics, 126 signal generation and data management,
funding for PV activities, 45, 103 Pharmaceutical companies 83, 84
gross domestic product (GDP), 19, 20 availability of forms, 91 as stakeholders, 82
health facilities, 81, 84, 85, 86, 87 communication technologies for PV, 90 Pharmacoepidemiology, 129
medical products, 57, 58 core reference materials, 90 Pharmacogenomics, 78–79
medicine information offices, 57 funding for PV, 90 Pharmacogenomics Network (Thailand),
medicine safety bulletins, 14–15, 57 medicine/device safety information 78
medicine safety regulatory actions, 59 requests, 92 Pharmacovigilance
medicines policy, 118 medicine safety alerts, 92 assessment of, 124
Medicines Safety Advisory Committee, 14 pharmacovigilance capacity, 92, 93 in civil society, 16, 97–100
national guidelines/standard operating policy, law, and regulation, 89 classification scheme, 101–102
procedures, 46 quality control units, 90 comparisons, 101–102
pharmaceutical industry, 41, 92, 93, 94 risk assessment and evaluation, 91, 92 country profiles, 110–113, 114–123
pharmaceutical market, 13, 20, 21 risk mitigation plans for high-risk data management, 51
pharmaceutical production, 118 medicines, 92 definition of, 21–23
pharmaceutical profile, 118 SOPs for PV and medicine safety, 90 essential statements on, 40
pharmacies, 84, 87 staff training, 90 funding, 17, 45, 46, 70–71, 79, 80
pharmacovigilance centers, 45 systems, structures, and stakeholder governance of, 14, 39–40, 110–113
pharmacovigilance governance, 39–40, coordination, 89–90 in health facilities, 81–88
110 Pharmaceutical industry, 15 in-service training curriculum, 88
pharmacovigilance performance, 101, 102 audits and inspections, 95 informing health workers about, 88
pharmacovigilance profile, 110–113, 119 availability of forms, 91 international collaboration and
pharmacovigilance system, 8, 16, 49, 65, commitment to PV, 18, 95 harmonization, 29–30
110–111 country profiles, 114–123 legal provisions, 40
policy, law, and regulation, 43, 110 internal policy statements, 89 national, 14–16, 16–17, 37, 40, 65
population, 20 legislation of, 41, 42–43 national capacity, 65
product quality assurance, 63 options for improving PV, 95 national guideline/operating procedures,
product register, 39 pharmacovigilance results, 89–95 46
professional associations, 99 policy, law, and regulation of, 89 national systems, structures, and
public communication activities, 58, 59 post-market surveillance of, 89 stakeholder coordination, 49
public health program, 76, 77, 78 pre-marketing activities, 73 options for improving, 88, 95, 100
quality control lab services, 46 recommendations and options for, 18 options for strengthening, 67–74
regional harmonization initiatives, 33 regulatory requirements, 41 in pharmaceutical industry, 15, 89–95

policy, law, and regulation of, 97, 110 pharmaceutical market, 20, 21 Product Development Partnership Access
pre-service training curricula, 47 pharmaceutical production status, 120 Group, 104
as public health priority, 18, 100 pharmaceutical profile, 120 Product life-cycle, 129
in public health programs, 15, 75–80 pharmacies, 82, 84, 86, 87 Product quality assurance
quality management systems, 48 pharmacovigilance, 102 indicators related to, 63
recognition of importance and practice of, pharmacovigilance centers, 45 legal provision for, 41
28–29 pharmacovigilance governance, 40, 110 Product quality reporting forms, 61, 91
reference materials, 47 pharmacovigilance profile, 110–113, 121 Product quality surveillance, 61–64
regulatory requirements, 41 pharmacovigilance requirements, 40 Product quality surveys, 129
regulatory systems, 27–35 pharmacovigilance system, 8, 16, 40, 49, Professional associations, 97, 98, 99
scope of, 21–23 65, 98, 110–111 Promoting Quality of Medicines (PQM),
in service delivery, 15, 81–88 policy, law, and regulation, 43, 110 103
staff training, 90 population, 20 Promotion, 42
study objectives and methods, 25–26 product quality assurance, 63 Public communication activities, 58, 59
systems for coordination and collation of product quality reporting forms, 61 Public health programs, 15
data, 51–53 product register, 39 curricular topics, 126
visibility of, 18 professional associations, 99 national, 77, 78
Pharmacovigilance centers or units, 45, 72 public communication activities, 58, 59 options for strengthening, 79–80
Pharmacovigilance guidelines, 71 public health programs, 77, 78 pharmacovigilance capacity, 77, 78
Pharmacovigilance systems, 45–50, 97, quality control lab services, 46, 62 pharmacovigilance funding, 79
110–111 quality management system, 14, 48 pharmacovigilance results, 75–80
capacity, 16 regional harmonization initiatives, 32, 33 policy, law, and regulation of, 75
challenges in Asia, 34–35 regulatory requirements, 41 recommendations and options for
comparative analysis of, 37 reporting of adverse events (AEs), 14, 53, strengthening, 17
components of, 101 73, 84 risk assessment and evaluation, 76, 79–80
comprehensive, 101 risk assessment and evaluation, 55, 56, risk management and communication,
definition of, 129 112 76–77
initiatives for strengthening, 103–104 risk management and communication, signal generation and data management,
options for strengthening, 79–80 14–15, 57–58, 59, 60, 112–113 75–76, 77
performance, 16 risk mitigation plans for high-risk systems, structure, and stakeholder
recommendations and options for medicines, 57–58 coordination, 75, 76
enhancing, 16–18 safety advisory committee, 47 PV Asia Network, 104
review of, 25 signal generation and data management,
Pharmacovigilance units/drug information 52, 53, 111 Q
centers, 47 sites visited, 124 Quality
Philippines unregistered medicines, 57 definition of, 130
cell phones, 72 WHO International Drug Monitoring falsified and substandard products, 17,
civil society, 97 Programme membership, 47, 49 73–74, 129
consumer groups, 99 WHO-UMC membership, 29 poor quality products, 33–34
consumer reporting forms, 84, 99 Policy, 14 Quality assurance, 34, 48
data management, 51 comparative analysis of, 40 definition of, 130
data mining methods, 51, 52 essential statements on PV or medicines essential statements on PV or medicines
funding for PV activities, 45 safety, 40 safety, 40
gross domestic product (GDP), 20 pharmaceutical industry, 89 legal provision for, 41
health facilities, 81–82, 84, 85, 87 public health programs, 75 options for improving, 73–74
legal provisions, 14 service delivery, 81 Quality control
medical products, 57, 58 Post-market commitments, 40 advisory committees, 47
medicine safety bulletins, 15 Post-market surveillance, 89 confronting falsified and substandard
medicine safety information processes, 57 Post-marketing alert (PMA) system products, 73–74
medicine safety regulatory actions, 59 (ASEAN), 32 lab services, 46
medicines profile, 120 Post-marketing surveillance, 129 of medical products, 57, 58
national guidelines/standard operating Pre-marketing activities, 73 national guideline/operating procedures
procedures, 46 Pre-service training curricula, 47 for, 46
national medicines legislation, 40 Prescription Drug User Fee Act (US), 71 Quality control laboratories or units, 46,
National Policy and Program on President’s Emergency Plan for AIDS Relief 61–62
Pharmacovigilance, 40, 67 (PEPFAR), 26, 80, 103 Quality management systems, 48
pharmaceutical industry, 41, 89, 92, 93, 94 Private pharmacies, 82 Quality surveillance, 61–64
index 141
in service delivery, 84 in public health programs, 75–76, 77
R sustainable, 79–80 in service delivery, 83, 84
Ranbaxy, 109 Risk identification, 125 Signals, 130
Rapid alerts, 74 Risk management, 130 Singapore, 21, 29, 31, 69, 108
Real-life effectiveness, 128 Risk management and communication South Asia Association for Regional
Recommendations and options, 16–18 civil society, 98 Cooperation (SAARC), 33, 69
Reference authorities, 30 curricular topics, 125 harmonization initiatives, 33
Reference materials, 47, 50 in health facilities, 85–86 South Asian Regional Standards
Regional centers, 72 national, 14–15 Organization (SARSO), 33, 69
Regional harmonization initiatives, 16, in pharmaceutical industry, 92 Sri Lanka, 29
30–33, 68–69 profiles, 112–113 Staff training, 17, 90
Regional initiatives, 103–104 in public health programs, 76–77 Stakeholders
Regional institutions, 104 risk mitigation plans for high-risk civil society, 97, 98
Regional regulations, 16, 67–68 medicines, 57–58, 63–64, 92 at national level, 14, 47, 48–50
Registries in service delivery, 85–86 pharmaceutical industry, 89–90
definition of, 130 Risk management plans (RMPs), 95, 130 pharmacies as, 82
regulatory, 39 in public health programs, 75, 76
Regulation, 14 S in service delivery, 81–82
civil regulations, 97 Safety Standard operating procedures, 46
convergent regional and international comparison of systems, 30, 31 Standards for reporting, 72
regulations, 16, 67–68 curricular topics, 125 State Food and Drug Administration
curricular topics, 125 definition of, 129, 130 (China), 28, 73
of devices, 18 guidelines for, 22 Statements on PV or medicines safety, 40
governance structures mandated by, 39–40 recommendations for, 18 Strengthening Pharmaceutical Systems (SPS)
international, 67–68 staff training, 90 Program, 25, 124
of medical devices, 95 statements on PV or medicines safety, 40 Substandard medicines, 17, 130
of medicines, 27–33 See also Medicine safety Substandard products, 73–74
of pharmaceutical industry, 41, 89 Safety advisory committees, 47 Surveillance, active, 128
of public health programs, 75 Safety alerts, 92 Suspect Adverse Reaction Report Form
reason for, 27 Safety bulletins, 14, 57, 85 (CIOMS Form I), 22
reduction of, 69–70 Safety Monitoring Program (SMP) Sustainable risk assessment and evaluation,
reforms, 108–109 (Thailand), 40, 42, 72–73 79–80
regional, 67–68 Safety reports, 22, 129 Systems for Improved Access to
service delivery, 81 Safety surveillance Pharmaceuticals and Services (SIAPS), 13,
strengthening regulatory policies and ensuring efficiency of, 69–70 103
frameworks, 16, 67 integrated, 17, 69
systems reviews, 25, 27–35 options for, 69, 70 T
Regulatory authorities, 28–29, 30, 130 Sentinel sites, 130 Taiwan, 71
Regulatory Harmonization Steering Serious adverse events, 130 Technical institutions and programs, 103–104
Committee (RHSC) (APEC), 30–32, 33 Service delivery Technology
Reporting options for improving PV, 88 communication technologies, 47, 50, 90
of ADRs, 53, 84 pharmacovigilance results, 15, 81–88 information technologies, 72
management of reports, 72 policy, law, and regulation of, 81 Thailand
mandatory, 40 recommendations and options for, 17–18 Adverse Drug Reaction’s Community of
options for strengthening, 72–73 risk assessment and evaluation, 84 Pharmacy Practice (ADCoPT), 55
spontaneous, 17, 55, 130 risk management and communication, adverse events (AEs) forms, 14, 53, 84, 99,
standards for, 72 85–86 127
strengthening, 17, 71–73 signal generation and data management, 83 adverse events (AEs) reporting, 14, 53, 71,
Reporting forms, 52–53, 72, 91, 100 systems, structure, stakeholder 73, 84
Risk assessment and evaluation coordination, 81–82 cell phones, 72
in civil society, 98 See also Health facilities; Pharmacies civil pharmacovigilance, 97
curricular topics, 125 SIGNAL (WHO-UMC), 34 consumer groups, 99
national level, 14, 55, 56 Signal generation and data management consumer reporting forms, 84, 99
in pharmaceutical industry, 91, 92 in civil society, 98 data management, 51
profiles, 112 national level, 14, 51–53 data mining methods, 51, 52
in public health programs, 76 in pharmaceutical industry, 91 drug trafficking, 27
recommendations for, 17 profiles, 111 funding for PV activities, 14, 45, 103

gross domestic product (GDP), 19, 20 WHO International Drug Monitoring drug safety alert system, 68–69
health facilities, 81–82, 84, 85, 86, 87 Programme membership, 47 Global Individual Case Safety Reports
Health Product Adverse Event Report form, WHO-UMC membership, 29 database, 34
127 Therapeutic goods administration (TGA) International Drug Monitoring
Health Product Vigilance Center (HPVC), (Australia), 70 Programme, 14, 22, 47, 50
45, 69, 72 Tolerability of medicines, 17 Pharmaceuticals Newsletter, 62
medical products, 57, 58 Training pharmacovigilance initiatives, 22, 23
medication mishaps, 108 for health workers, 17 rapid alert systems, 34, 74
medicine safety bulletins, 14–15, 57 in-service, 88 regulatory reforms, 108
medicine safety information processes, 57 pharmacovigilance topics, 125–126 VigiBase, 104, 130
medicine safety regulatory actions, 59 pre-service, 47 voluntary notification scheme, 27
medicines policy, 122 for staff, 17, 90 Western Pacific Region (WPRO) rapid alert
Medicines Safety Advisory Committee, 14, Treatment failure, 130 system, 34
47 Tuberculosis (TB), 21, 126
national guidelines, 14, 46, 97
National Health Security Office (NHSO), U
53 UMC, 104
national public health program, 78 UNESCO, 22
NRA, 14 UNITAID, 103
Performance Management and Quality United Kingdom, 68–69, 70
Assurance system, 48 United States
pharmaceutical industry, 41, 89, 92, 93, 94 Code of Federal Regulations, 30
pharmaceutical market, 13, 20, 21 drug safety system, 30, 31
pharmaceutical production status, 122 Federal Food, Drug and Cosmetic Act, 27,
pharmaceutical profile, 122 108
pharmacies, 82, 84, 86, 87 Food and Drug Administration
Pharmacogenomics Network, 78 Amendments Act (FDAAA), 30, 108
pharmacovigilance centers, 45 funding for PV, 71
pharmacovigilance performance, 102 Institute of Medicine (IOM), 70
pharmacovigilance profile, 110–113, 123 medication mishaps, 109
pharmacovigilance system, 9, 16, 40, 49, 65, Prescription Drug User Fee Act (PDUFA),
110–111 71
policy, law, and regulation, 43, 110 regulatory reforms, 108
population, 20 United States Pharmacopeia, 104
product quality assurance, 61, 63 University of Science and Technology
product quality reporting forms, 61 (Bangladesh), 53
product quality surveys and inspections, 61 Unregistered medicines, 14–15
product register, 39 Uppsala Monitoring Centre (WHO), 29, 103,
professional associations, 98, 99 104
public communication activities, 58, 59 US Agency for International Development
public health programs, 15, 76 (USAID), 13, 25, 103, 109
quality control laboratories, 14, 46, 62
quality management system, 48 V
regional harmonization initiatives, 32, 33 Vaccines, 104, 126
regulatory requirements, 41 Vietnam, 21, 27, 29, 103, 108
risk assessment and evaluation, 55, 56, 112 VigiBase (WHO), 104, 130
risk management and communication, VigiFlow, 130
14–15, 57–58, 59, 60, 112–113
risk mitigation plans for high-risk W
medicines, 57–58 Western Pacific Region (WPRO) rapid alert
Safety Monitoring Program (SMP), 40, 42, system (WHO), 34
72–73 WHO-ART, 130
signal generation and data management, 52, WHO-UMC, 29, 34, 103
53, 111 World Health Organization (WHO)
sites visited, 124 Advisory Committee on the Safety of
surveillance activity, 14 Medicinal Products, 103
unregistered medicines, 57 definition of PV, 21–22
index 143

Pharmacovigilance in Asian Countries

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C O M PA R AT I V E Pharmacovigilance Systems

Systems for Improved Access to Pharmaceuticals and Services

The assessment on pharmacovigilance system and its performance in Cambodia indicates

ADR adverse drug reaction

United States of America

Review, Project Coordination, Guidance

US Food and Drug Administration (FDA)

Access to medicine is improving in low- and middle-income countries (LMICs), thanks to

Current State of Pharmaceutical Market in Asia

Signal Generation and Data Management

Risk Assessment and Evaluation

Risk Management and Communication

Pharmacovigilance in Public Health Programs For all countries,

Pharmacovigilance at the Service Delivery Level

Pharmacovigilance in the Pharmaceutical Industry

Selected Recommendations and Options for

Ensure Convergent Regional and International Regulations

Improve Information Sharing and Participation in Regional

Improve Funding for PV

Strengthen Spontaneous Reporting

Confront Falsified and Substandard Medicines

Public Health Programs Level

Develop Sustainable Risk Assessment and Evaluation Activities

Include PV in Donation Programs

Health Facilities and Services Delivery Level

Background on Asian Pharmaceutical Market

Figure 1. Map of Asian Countries Included in Assessment

SRI LANKA BRUNEI

Pharmaceutical Market Size

Definition and Scope of Pharmacovigilance

Table 2. Functions of Select PV Initiatives

1. Review of regulatory and PV systems

1. Review of Regulatory and PV Systems

2. Individual Country Assessments

3. Comparative Analysis of Results from Individual Country Studies

As access to medicines improves, the value of strengthening PV systems is becoming

Recognition of Importance and Practice of Pharmacovigilance

Table 3. WHO-UMC Membership Status

International Collaboration and Harmonization

Comparison of Pharmacovigilance Practices of Stringent Regulatory

Regional Harmonization Initiatives in Asia

Regulatory Stringent NRAs Asian competent/reference NRAs

Table 5. Countries of Manufacture of Cambodia Registered Products

Table 6. Regional Harmonization Initiatives Member Countries

Poor Quality Products

Challenges for Pharmacovigilance Systems in Asia

Pharmacovigilance at the National Level

§§ Existence of regulatory framework

Existence of Regulatory Framework

Existence of Regulatory Registries

Governance Structures Mandated by Regulations and in Practice

Table 7. PV Governance at the National Level

Policy, Law, and Regulation

Legal Provision for PV in the National Medicines Legislation

Provisions That Mandate Market Authorization Holders to

Legal Provision for Product Quality Assurance

Table 9. Content Analysis of Pharmaceutical Legislation

Legal Provision for Control of Promotion and Advertisement

frameworks define countries’ pharmaceutical regulation and governance, and include

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