Afghanistan Medicines Sampling and Testing – A ...apps.who.int/medicinedocs/documents/s20276en/s20276en.pdf · Afghanistan Medicines Sampling and Testing – A Quantitative

ISLAMIC REPUBLIC OF AFGHANISTAN MINISTRY OF PUBLIC HEALTH

GENERAL DIRECTORATE OF PHARMACEUTICAL AFFAIRS

Afghanistan Medicines Sampling and Testing – A Quantitative Survey

April 2011


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April 2011

Wahidullah Karwar

Mohammad Zafar Omari Zakeria Fatehzada

Aisha Noorzaee Inua Yusuf David Lee

Mark Morris Tom Layloff

Strengthening Pharmaceutical Systems Center for Pharmaceutical Management

Management Sciences for Health 4301 N. Fairfax Drive, Suite 400

Arlington, VA 22203 USA Phone: 703.524.6575

Fax: 703.524.7898 E-mail: [email protected]

mailto:[email protected]


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This report is made possible by the generous support of the American people through the United States Agency for International Development (USAID), under the terms of Cooperative Agreement No.GHN-A-00-07-00002-00. The contents are the responsibility of Management Sciences for Health and do not reflect the views of USAID or the United States Government. About SPS The Strengthening Pharmaceutical Systems (SPS) Program strives to build capacity within developing countries to effectively manage all aspects of pharmaceutical systems and services. SPS focuses on improving governance in the pharmaceutical sector, strengthening pharmaceutical management systems and financing mechanisms, containing antimicrobial resistance, and enhancing access to and appropriate use of medicines. Recommended Citation This report may be reproduced if credit is given to SPS. Please use the following citation. Wahidullah Karwar, M. Zafar Omari, Zakeria Fatehzada, Aisha Noorzaee, Inua Yusuf, D. Lee, M. Morris, and T. Layloff. April 2011. Afghanistan Medicines Sampling and Testing – A Quantitative Survey. Submitted to the USAID by the Strengthening Pharmaceutical Systems (SPS) Program. Arlington, VA: Management Sciences for Health. Strengthening Pharmaceutical Systems 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] Web: www.msh.org/sps


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CONTENTS Acronyms and Abbreviations ........................................................................................................ vi

Acknowledgments......................................................................................................................... vii

Commentary…………………………………………………………………………………….....8

Executive Summary ........................................................................................................................ 9 Introduction .................................................................................................................................. 9 Methodology ................................................................................................................................. 9 Key Findings ................................................................................................................................ 9 Conclusion .................................................................................................................................. 10 Recommendations ...................................................................................................................... 10

Introduction ................................................................................................................................... 11

General Overview of Afghanistan Pharmaceutical sector ............................................................ 12 Islamic Republic of Afghanistan in Brief ................................................................................... 12 The Afghanistan Pharmaceutical Market ................................................................................... 12 The MoPH Commitment to Strengthening the Pharmaceutical Sector ...................................... 14 Need for this Medicines Testing Survey .................................................................................... 14

Methodology ................................................................................................................................. 17 Survey Planning and Implementation ........................................................................................ 17 Challenges of the Medicines Sampling and Testing .................................................................. 17 Medicines Sampling and Analysis ............................................................................................. 17 Training for Field Sample Collectors ......................................................................................... 19 Collection of Medicines for Analytical Testing ......................................................................... 19 Coding of Samples ..................................................................................................................... 23 Packaging and Labeling ............................................................................................................. 23 Laboratory Testing ..................................................................................................................... 24 Storage and Transportation of Samples ...................................................................................... 25 Data Entry and Analysis ............................................................................................................. 25

Results of Medicines Sampling and Testing ................................................................................. 26 Countries of Origin and Manufacturers ...................................................................................... 26 Findings of Analytical Testing ................................................................................................... 26 Passed Samples ........................................................................................................................... 27 Failed Samples ............................................................................................................................ 28 Findings of Analytical Testing by Province, Manufacturer and Country .................................. 29 Findings of Analytical Testing by Individual Medicines ........................................................... 30

DISCUSSION ............................................................................................................................... 33 Source of Failed Samples ........................................................................................................... 33 Nature of Test Failures and Potential Solutions ......................................................................... 33 The GPHF Minilab® Testing ..................................................................................................... 33 Process of Assuring the Quality of Medicines ........................................................................... 34

Conclusion .................................................................................................................................... 36

RecommendationS ........................................................................................................................ 37


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Annex A. NAMES AND AGENCIES OF SAMPLE COLLECTION TEAM MEMBERS ........ 38

Annex B. Afghanistan Demographic Data ................................................................................... 40

Annex C. National Consumption and Cost of Selected Medicines for Analytical Testing .......... 41

Annex D. Distribution of Provinces for Sample Collection ......................................................... 42

Annex E. Analytical laboratory testing carried out on medicines ................................................ 43

Annex F. List of Manufacturing Companies of Medicines Collected and Tested in January 2010 ....................................................................................................................................... 45

Annex G. Licensed Drug List and Essential Drug List OF Medicines that have Thin-layer chromatography methods .............................................................................................. 47

List of Figures Figure 1. Distribution of samples collected and tested by sector and donor-support ................... 21 Figure 2. Countries of origin of medicines collected and tested in January 2010 ........................ 26 Figure 3. Distribution of samples passing analytical testing by health facility ............................ 27 Figure 4. Distribution of samples failing analytical testing by health facility .............................. 28 Figure 5. Distribution of failed samples by provinces by number and percentage....................... 29 Figure 6. Percentages of failed samples by country of origin ....................................................... 29 Figure 7. Results of individual medicines collected and tested in January 2010 ......................... 32 List of Tables Table 1. Total number of units per sample collected for laboratory testing in January 2010 ...... 20 Table 2. Field sample validation tool ............................................................................................ 20 Table 3. Samples collected from selected sites in the provinces for laboratory analytical testing in January 2010 ................................................................................................................................. 22 Table 4. Permutation diagram for sample collection in January 2010 ......................................... 23 Table 5. Coding system for sample collected and tested in January 2010 ................................... 23 Table 6. Results of laboratory analytical testing of medicines in January 2010 ........................... 26 Table 7. Samples passing laboratory analytical testing by sector and donor support................... 27 Table 8. Samples failing laboratory analytical testing by sector and donor support .................... 28 Table 9. List of manufacturing companies of failed samples in January 2010............................. 30 Table 10. Minilab ® Thin Layer Chromatography (TLC) Method Coverage of Licensed Drug List and Essential Drug List.* ....................................................................................................... 47 Table 11. Additional Active Ingredients of Medicines in Licensed Drug List that are covered by Unofficial Thin Layer Chromatography Methods** .................................................................... 48


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ACRONYMS AND ABBREVIATIONS API Avicenna Pharmaceutical Institute BHC Basic Health Center BPHS Basic Package of Health Services CHC Comprehensive Health Center DH District Hospital DFID Department for International Development (U.K.) EC European Commission EDL Essential Drug List EPHS Essential Package of Hospital Services EU European Union FDQCD Food and Drugs Quality Control Department GDPA General Directorate of Pharmaceutical Affairs GPFH German Pharma Health Fund LDL Licensed Drug List MoPH Ministry of Public Health MRA Medicines Regulatory Authority MSH Management Sciences for Health NFMB National Food and Medicines Board NGO Nongovernmental Organization NMP National Medicine Policy OC Oral Contraceptives ORS Oral Rehydration Salts PrH Private Hospital Ph. Int. International Pharmacopoeia PrPh Private Pharmacy QATF Quality Assurance Task Force RH Regional Hospital SCMS Supply Chain Management System SH Specialty Hospital SPS Strengthening Pharmaceutical Systems (Program) TLC Thin-Layer Chromatography USAID U. S. Agency for International Development USD U. S. Dollar USP U. S. Pharmacopeia WB World Bank WHO World Health Organization ZL Zentral Laboratorium


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ACKNOWLEDGMENTS This sampling and testing of medicines survey is the result of the efforts of several individuals, and public and private sectors agencies based in Afghanistan. The survey received tremendous support from HE Minister of Public Health (Dr. Sayed Mohammad Amin Fatemi), HE Deputy Minister of MoPH for Technical Affairs (Dr. Faizullah Kakar), and General Director of Pharmaceutical Affairs (Pharmacist Jamahir Anwari). Annex A shows the officials that took part in the sample collection process. All these individuals, the agencies, and their officials provided invaluable support to the process. Niranjan Konduri, Angelica Perez, Martha Embrey and Susan Brock reviewed the draft report and provided very useful technical comments and observations. The public and private sector organizations which were directly involved in the sample collection, storage, transportation and analysis process include—

• Basic Health Centers • Comprehensive Health Centers • Customs Directorate, Ministry of Finance • District Hospitals • General Directorate of Pharmaceutical Affairs (GDPA) • Global Express and Logistics Company • Government Pharmacies • Health Laws and Regulation Directorate (now known as Legislation Implementation

Ensuring Department (LIED) of MoPH) • Ministry of Public Health • Pharmaceutical Enterprise • Private Hospitals • Provincial Health Directorates • Provincial Hospitals • Quality Assurance Task Force • Regional Hospitals • Specialty Hospitals • Strengthening Pharmaceutical Systems Program (SPS) • Tech-Serve Project Afghanistan



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EXECUTIVE SUMMARY Introduction The Afghanistan Ministry of Public Health (MoPH), with technical assistance from the Strengthening Pharmaceutical Systems (SPS) Program, carried out a survey of medicines quality in Afghanistan. The survey was conducted for the MoPH to determine whether medicines in the public and private sectors of Afghanistan comply with established international pharmacopeial standards. The findings of this quantitative survey, together with the findings of a separately conducted qualitative medicines quality assurance assessment survey in Afghanistan, will lead to the development of policies and strategies for a sustainable medicines quality assurance system for the country. Methodology The medicines sampling and testing survey was designed to achieve a representative sample of each type of health facility—private-for-profit and public; provinces—in secure urban and rural areas of the country; sources of funding—mainly U. S. Agency for International Development (USAID), World Bank (WB), European Union (EU); and supply sources—national and international. A total of 348 medicine samples were collected and tested from both the private and public sectors. A total of 169 samples were collected from the private sector and 179 samples were collected from the public sector. Each sample of injection and powder forms was comprised of 10 units, and each sample of tablet and capsule form was comprised of 100 units. Batch numbers were used as the key identifier for differentiating samples. Key Findings The largest suppliers of collected medicine samples are Pakistan (24 percent), India (20 percent), Iran (17 percent), and China (11 percent). Six major manufacturing companies out of a total of 145 are Exir Pharmaceuticals (18 samples), Wyeth (15 samples), Medicamen Biotech (12 samples), Davis Pharmaceutical (11 samples), Gland Pharma (10 samples), and Merck (9 samples). Out of 348 medicines collected and tested in the laboratory, 315 (91 percent) passed and 33 (9 percent) failed to meet United States Pharmacopeia (USP) and International Pharmacopeia (Ph. Intl) standards. Ninety-two percent of medicines collected and tested from the private sector met pharmacopeial standard and 8 percent failed to meet the standard. The 8 percent represents 14 failed samples from all the 169 samples collected and tested from the private sector. Six (7 percent) out of 84 samples collected from private hospitals, and 8 (9 percent) out of 85 samples collected from private pharmacies failed to meet USP and Ph. Intl. standards. Eighty-nine percent of medicines collected from the public health facilities (public sector) met USP and Ph. Intl. standards, while 11 percent failed. . The 11 percent represents 19 failed samples from the 179 samples collected and tested from the public sector. Seven (11 percent) out of 63 samples collected from USAID-supported public health facilities failed analytical testing. Six (15 percent) out of 41samples from WB-supported facilities, 4 (11 percent) out of 36 samples collected from EU-supported public health facilities and 2 (6 percent) out of 31 samples from MoPH facilities failed to


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meet USP and Ph, Intl standards. Samples collected from donor-supported public health facilities were not confirmed products supplied by the respective donors. Of the 33 medicines that did not meet test requirements, 19 percent were found in Balkh and Nangarhar provinces. Herat province recorded 16 percent of substandard medicines. Kandahar province had the least (6 percent) percentage of failed products. A total of 22 manufacturing companies produced the medicines that failed to meet pharmacopeial standards. The substandard medicines originated from 11 countries. Conclusion Substandard products are found in both the public (government and donor-supported) and the private (for-profit) sectors. Findings relate primarily to the better regulated segment of the Afghanistan pharmaceutical market but measures are still needed to reduce the observed 9 percent test failure rate. A comprehensive but realistic and sustainable strategy is needed to assure the quality of medicines in Afghanistan. Recommendations

• The MoPH should conduct a feasibility analysis for implementing a sustainable risk-based medicines quality screening program and the development of a national quality assurance program.

• The MoPH should develop a national strategy for medicines quality assurance which should

include registration of medicines products, inspection and enforcement of registration status, risk-based sampling and screening with the Minilab® for a number of medicines, confirmatory testing with legal pharmacopeial reference methods, and product problem reporting by healthcare providers and the community.

• The national strategy for medicines quality assurance should include appropriate actions in the

public, the non-governmental organization (NGO) and the private for-profit sectors, based on broad stakeholder consensus and support.


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INTRODUCTION Medicine product quality and integrity have been identified as major concerns in several countries, especially in developing countries where assessments were performed.1 Adequate medicines legislation and regulations, a competent Medicines Regulatory Authority (MRA), and appropriate medicine information are required to ensure the safety, efficacy, and high quality of medicines.2 Since pharmaceuticals frequently are expensive and therefore prone to counterfeiting and substandard production, the establishment of a viable and sustainable market protection through regulatory processes is essential. These processes must be capable of detecting substandard products to help provide a deterrent to unscrupulous manufacturers and suppliers. Previous studies of the pharmaceutical sector of Afghanistan provide some insight into the medicines quality assurance situation in the country. However, there are gaps in the scope and approach to determining whether substandard or counterfeit products exist in the marketplace, per pharmacopeial standards. The Strengthening Pharmaceutical Systems (SPS) Program’s survey was performed to assist the Ministry of Public Health (MoPH) to determine whether medicines in both the public and private sectors of Afghanistan comply with established international pharmacopeial standards, leading to the development of strategies for a sustainable medicines quality assurance system for Afghanistan. The Afghanistan Medicines Sampling and Testing Study included three key objectives which were to—

• Determine the quality of medicines in the private hospitals and private pharmacies; • Determine the quality of medicines in the public health facilities supported by the U. S.

Agency for International Development (USAID), World Bank (WB), and European Union (EU); and

• Make recommendations to the MoPH policy makers and authorities responsible for designing and developing the appropriate medicines quality assurance system.

1 SEAM Conference 2001. Roundtable #6: Ensuring Drug Product Quality. www.msh.org/seam/conference2001/roundtable6.html 2 Paterson, A. and A. Karimi. 2005. Understanding Markets in Afghanistan: A Survey of the Market for Pharmaceuticals. Kabul: Afghanistan Research and Evaluation Unit.

http://www.msh.org/seam/conference2001/roundtable6.html


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GENERAL OVERVIEW OF AFGHANISTAN PHARMACEUTICAL SECTOR Islamic Republic of Afghanistan in Brief The Islamic Republic of Afghanistan has experienced a continuous state of civil war that has grossly affected national development and health indicators.3 Afghanistan had an estimated population of 25.5 million as of October 2009, which was predominantly rural (77.1 percent). Life expectancy for both men and women is 44 years. Total annual government health expenditure is 162 million U.S. Dollars (USD), of which, USD135 million comes from international aid in 2009. The country is endowed with several public sector health facilities of varying levels of complexity, from basic health centers to specialty hospitals. The majority is comprehensive health centers (CHCs) (372) and basic health centers (BHCs) (779). There are 174 private hospitals in Afghanistan (Annex B). The Afghanistan Pharmaceutical Market Total government expenditure and per capita expenditure for the pharmaceutical sector are not known. Similarly, the total value of domestic pharmaceutical production and imports and exports of active pharmaceutical ingredients and finished pharmaceutical products is not known. This is attributed to the lack of a data base or credible source for collecting this information. However, the MoPH/General Directorate of Pharmaceutical Affairs (GDPA) estimates that annually, the private-for-profit and private-not-for-profit (NGOs) sectors hold medicines worth USD80 million and USD20 million respectively. However, other sources estimate that the private-for-profit sector accounts for between 70 and 80 percent of total pharmaceutical consumption and that the annual market may be worth up to USD200 million.4 According to the World Health Organization (WHO) (2002), the MoPH is not in a position to adequately control the quality of medicines entering the market. Regular and periodic testing of medicines is critical to controlling the quality of medicines in the country. A well-equipped laboratory with adequate equipment and well-trained human resources can contribute significantly to an efficient registration and licensing process. Afghanistan’s national medicines quality control laboratory is operating under challenging conditions in a dilapidated structure. The facility is not internationally accredited. It operates without any formal international quality control laboratory cooperation. Major technical and financial assistance would be required to reconstruct and restructure the pharmaceutical sector into one that would offer the appropriate level of services critically needed by the population. Building up the pharmaceutical sector would take years and would require long-term commitment from any partner involved in the country.5 However, since 2002, there has been a number of positive sector developments, particularly concerning the introduction of

3 http://www.unfpa.org/emergencies/afghanistan/factsheet.htm and http://www.who.int/countries/afg/en/ 4 Ibid. 5 Baghdadi, G. et al. Pharmaceutical Situation in Afghanistan

http://www.unfpa.org/emergencies/afghanistan/factsheet.htm

http://www.who.int/countries/afg/en/


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the donor-funded BPHS/EPHS providing essential medicine coverage to the population and the putting in place of basic policy and regulatory systems and structures. The U. K. Department for International Development (DFID) (2005) states that in Afghanistan, profit margins at the point of import, wholesale and retail, are technically capped by the government at between 8 and 15 percent. But almost all players admitted that this was not followed in practice. Many medicines on the market are cheap, but of substandard quality, as market players opt for cheaper products to meet the demand of poor Afghanistan customers. The number of players is larger at every point in the supply chain than in other markets studied. The European Commission (EC) states in its 2008 report that the Basic Package of Health Services (BPHS)/Essential Package of Hospital Services (EPHS) system has made several achievements since it was established in 2003, but the system is highly complex and suffers from lack of coordination among the government, the MoPH, and the international donor community that funds it.6 There are weaknesses in providing essential medicines through the BPHS/EPHS scheme. It is not clear what level of coverage the system is supposed to achieve in terms of supplying essential medicines to the population in need. At least 70 percent of essential medicines are provided through the private sector in spite of the BPHS/EPHS system. The EC report goes on to state that irrespective of the clear inadequacies that exist in the pharmaceutical policy and regulation system in Afghanistan, particularly with respect to a lack of enforcement, what the government and the international development community operating in Afghanistan both do not yet realize is that there is an increasing global threat from pharmaceutical crime.7 Unsubstantiated reports suggest that Afghanistan is a “pharmaceutical dustbin” of substandard, counterfeit, adulterated, and diverted medicines as well as a transit point for such medicines for the entire region. Afghanistan’s adverse economic and geopolitical situation makes it a strong target for pharmaceutical crime.

The EC further states that although many least developed countries in the world are now making serious efforts to implement international pharmaceutical regulatory and policy standards, Afghanistan is a long way from doing so. Some of the government policies actively encourage pharmaceutical crime. For example, international pharmaceutical manufacturers that produce branded and innovative medicines are arbitrarily forbidden, in contravention of international intellectual property agreements (i.e., World Trade Organization and Trade Related Aspects of Intellectual Property Rights) to trade in Afghanistan and thus their products are not surprisingly widely traded as counterfeits in Afghanistan, a situation which not only seriously damages Afghanistan’s public health but also undermines the entire legitimate international pharmaceutical business. As of December 2010, there are estimated 868 pharmacists and 769 pharmacy technicians in the public/NGO sector.8 There is no clearly separate information about the number of pharmacists and pharmacy technicians in the NGO sector. There is no data on the number of pharmacists working in the private sector. Afghanistan has one school for training pharmacists and an

6 Harper, J. and A. Shahab. Draft Afghanistan Pharmaceutical Sector Identification Mission Report, Intervention Scenarios for EC, November 2007 – January 2008. 7 Harper, J., and B. Gellie. 2006. Counterfeit Medicines-Survey Report. Strasbourg, France: Council of Europe. 8 General Directorate of Human Resource & General Directorate of Pharmaceutical Affairs of the MoPH.


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Institute of Health Science in Kabul where pharmacy technicians graduate from after two years of education. There has been a dramatic increase in the quantity of donated and privately imported medicines entering Afghanistan since 2002, according to MoPH and WHO sources. Furthermore, it is expected that Afghanistan will rely on donations of medicines for a number of years to come. The MoPH Commitment to Strengthening the Pharmaceutical Sector The MoPH has the responsibility to ensure that each medicine being distributed in the country is safe, effective, and of standard quality. The Ministry has for some time now demonstrated strong commitment to strengthening the pharmaceutical sector. For example, the MoPH has continuously supported the pharmaceutical and laboratory services despite its budgetary challenges. Furthermore, the Quality Assurance Task Force (QATF) was established at the MoPH to lead the process of developing appropriate strategies for medicines quality assurance for the country. Need for this Medicines Testing Survey A wider and comprehensive medicines testing in Afghanistan was necessitated by observed gaps in previous assessments of the pharmaceutical sector. The scope of previous studies varied, and the results had conflicting conclusions, some of which were drawn from anecdotal or unsubstantiated positions. Based on anecdotal comments, the EC (2008) report concluded that counterfeit medicines were likely to make up a large part of the Afghanistan pharmaceutical market, and the situation was completely out of control in all respects. The report recommended a comprehensive Afghanistan pharmaceutical sector study.

The DFID (2005) study, also based on anecdotal comments, concluded that there is a large amount of both substandard and outright fake medicines on the Afghan market. The scope of the assessment was very narrow, conducted in the private sector only and in a small number of provinces.9 Though not substantiated, the WHO (2002) report stated that the consumption of substandard quality and ineffective medicines procured from the private and public facilities in Afghanistan was widespread. According to WHO report, the MoPH was not in a position to adequately control the quality of medicines entering the market. Regular and periodic testing of medicines was therefore critical to controlling the quality of medicines in the country. In contrast, the JHU (2007) study concluded that Afghanistan did not face a large problem of substandard medicines. The JHU study results were based on medicines analytical testing from

9 Paterson and Karimi, 2005. “Understanding markets in Afghanistan: A study of the market of Pharmaceuticals”, Afghanistan Research and Evaluation Unit.


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only BPHS health facilities and a small sample of medicines from private pharmacies in five major urban centers.10

The EC (2008) Report: The EC carried out an assessment of the pharmaceutical sector in 2007–2008. The report examined all aspects of Afghanistan pharmaceutical sector functioning—market operations and financing, policy and regulation conduct, pharmaceutical donor activities in the sector as well as drawing on international comparisons. The methodology for conducting the EC Pharmaceutical Sector Identification Mission was based on the review of documentation and reports, meetings with key sector stakeholders, site visits to local manufacturers, pharmacies, distributors and health care facilities both in the public and private sector, and review of current international pharmaceutical policy and regulatory standards and practices. Laboratory analytical testing of medicines was not carried out.

The report stated that the Afghanistan pharmaceutical market situation was completely out of control in all respects. Afghanistan was far from meeting international pharmaceutical regulatory and policy standards and practices or from guaranteeing medicine quality, safety, and efficacy. The report further pointed that some of the government policies actively encourage pharmaceutical crime. Though not substantiated, the EC study states that Afghanistan is a receptacle for substandard, counterfeit, adulterated, and diverted medicines. The assessment did not attempt to determine if medicines complied with standards through product quality testing. Based on anecdotal comments, the EC report concluded that counterfeit medicines were likely to make up a large part of the Afghanistan pharmaceutical market, and the situation was completely out of control in all respects. The report further stated that Afghanistan had a serious public health and trade problem concerning medicine and recommended a comprehensive Afghanistan pharmaceutical sector study.

The Johns Hopkins (JHU)(2007) Report: In 2007, the MoPH assessed the standard of medicine quality in BPHS health facilities with technical support from the Johns Hopkins University (JHU) Bloomberg School of Public Health and the Indian Institute of Health Management Research.11 The study looked at the public sector health care delivery system and a small sample of medicines from private pharmacies in five major urban centers. The results of this study showed that Afghanistan does not face a large problem of substandard medicines. The report however states that the small sample size from the private sector precludes one from drawing sweeping conclusions about the extent of substandard medicines in the for-profit private pharmaceutical market. These findings should not provide a false sense of security, especially in the absence of effective regulation. The DFID (2005) Report: The DFID supported an explorative study of the pharmaceutical sector in 2005 to gain insight into the experiences of Afghan business people in the private 10 Drug Quality Assessment Study Afghanistan. 2007. Ministry of Public Health, Islamic Republic of Afghanistan in Collaboration with the Johns Hopkins University, Blomberg School of Public Health and Indian Institute of Health Management Research. 11 Peters, D., A. A. Noor, L.P. Singh, et al. 2007. A balanced scorecard for health services in Afghanistan. Bulletin of the World Health Organization 85:146-151.


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pharmaceuticals market. The report stated that there had been a dramatic increase in the quantity of both donated and privately imported medicines entering Afghanistan since 2002.12 In addition, there was widespread smuggling of medicines. The proportion of smuggled medicines may have been as high as 80 percent of medicines sold in the private sector. The pharmaceuticals market was in chaos, and there was a bewildering array of products on sale. Low quality and counterfeit medicines containing insufficient or no active ingredients were also found in the market. The report concluded that inspection, sampling, and testing facilities were inadequate to secure basic standards of medicines on the market. The assessment was conducted in the private sector in a small number of provinces, using semi-structured interviews. The WHO (2002) Report: A WHO team conducted a preliminary assessment of the pharmaceutical situation in Afghanistan in 2002. The assessment included visits to a small number of manufacturing plants, warehouses, and the control laboratory—all located in Kabul. According to the WHO study, the overall pharmaceutical situation in Afghanistan has deteriorated dramatically during the last 20 years, leading to a lack of most of the essential drugs in public health facilities. The health infrastructure was seriously damaged and some buildings were completely destroyed, making it difficult for the staff to maintain professional standards. Though not substantiated, the report states that the consumption of substandard quality and ineffective medicines procured from the private and public facilities was widespread. There was a huge influx of donated medicines to the country. According to WHO report, the MoPH was not in a position to adequately control the quality of medicines entering the market. Regular and periodic testing of medicines was critical to controlling the quality of medicines in the country. A well equipped laboratory with adequate equipment and well trained human resources could contribute significantly to an efficient registration and licensing process.13

12 Paterson et al. Understanding Markets in Afghanistan. 13Jonathan Harper and Abdurrahman Shahab. Draft Afghanistan Pharmaceutical Sector Identification Mission Report, Intervention Scenarios for EC, November 2007 – January 2008.


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METHODOLOGY Survey Planning and Implementation The survey for medicines sampling and testing was jointly carried out by the MoPH/ GDPA and the SPS Program. The QATF, mandated by the MoPH, led the planning and implementation process with technical assistance from SPS Afghanistan and a team of external consultants. Approval for this survey was secured from the MoPH and USAID. Challenges of the Medicines Sampling and Testing This analysis is based on collected samples of medicines for testing in the laboratory. The medicines sampling and testing survey did not intend to establish the prevalence of substandard and/or counterfeit medicines, neither was it intended to quantify the extent of the problem. It was performed to determine whether there were substandard or counterfeit essential medicines in health facilities in the public or donor-supported sector and in the private-for-profit sector. The survey did not track product origin, storage condition, or in many instances credible mechanisms of establishing the real sources of the medicines collected. The survey only collected the samples from the various health facilities and recorded available information on the packages. Background information on the samples was collected strictly and exclusively from the respective packages of the samples. The full complement of samples could not be collected primarily due to the lack of availability of many of the target medicines at the selected sites, and because of lack of security in many parts in the country, it was not possible to go to many alternate sites for sample collection. Medicines Sampling and Analysis Eleven (11) tracer medicines of different dosage forms were selected for sampling and testing, based on their high national consumption, high cost, and therapeutic importance (Annex C). The medicine samples were collected simultaneously from selected sites from August to September 2009. These were clearly distinguished and packaged for analytical testing in a primary laboratory where all the medicines were tested, and in a secondary laboratory where some medicines were selected for parallel testing. Samples of 11 different medicines were collected from both the public and private sectors. The samples were collected using the generic names of the medicines. These were—

• Amoxicillin 250 mg or 500 mg Capsule • Omeprazole 20 mg Capsule • Alprazolam 0.5 mg Tablet • Atenolol 50mg or 100 mg Tablet • Levonorgestrel/Ethinyl Estradiol 0.25/0.05 mg or 0.30/0.03 mg Tablet • Paracetamol 500 mg Tablet • Ciprofloxacin 500 mg Tablet


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• Ceftriaxone 0.5 g or 1g Injection • Gentamicin 40 mg or 80 mg Injection • Medroxyprogesterone Acetate Depot 150 mg/ml Injection • Oral Rehydration Salt Powder

Sampling of facilities to collect samples of medicines for quality testing was based on a purposive representation of—

• Type of health facility—private and public • Provinces—secure areas of the country (Annex D) • Sources of funding—USAID, WB, and EU • Sources of supply—national and international

A total 64 health facilities of various categories and levels were selected as sites for sample collection—8 private hospitals, 8 private pharmacies, 8 specialty/provincial/regional hospitals, 8 district hospitals, 16 comprehensive health centers and 16 basic health centers.

The health facilities were grouped to achieve a proportional balance between the private and public sectors. The health facilities were also grouped to achieve a geographical balance in the secure areas of the country. The Private Hospital (PrH) and Private Pharmacy (PrPh) group represented the private sector, while the other group made up of the Specialty Hospitals (SH), Provincial Hospitals (PH), Regional Hospitals (RH), and District Hospitals (DH), together with Comprehensive Health Centers (CHC) and Basic Health Centers (BHC) represented the public sector.

The public health facilities were further grouped to achieve a proportional balance in accordance with the major funding sources in Afghanistan. One group of MoPH public health facilities were selected from four provinces having the majority of public health facilities receiving technical, financial or logistic support from the USAID (USAID-supported health facilities), and a second group of MoPH public health facilities were selected from four different provinces having the majority of public health facilities receiving technical, financial or logistic support from the WB and EU (WB- and EU-supported health facilities). Details of the supply chain, technical, financial or logistical support to the public health facilities were not recorded.

The medicine samples were grouped into four categories for testing—PrH, PrPh, public health facilities supported by USAID, and public health facilities supported by the WB and EU at different levels of care.14 A group of samples with similar characteristics was sent to a secondary laboratory, Zentral Laboratorium (ZL) in Germany, for parallel analytical testing. Of the eleven products selected for testing 3 products - Atenolol tablets, Levonorgestrel/Ethinyl Estradiol tablets (oral contraceptive—OC) and Oral Rehydration Salts (ORS) - were selected for parallel testing. The samples were considered cost-effective for the purpose of cross-checking the analytical results from the primary laboratory, in accordance with expert advice.

14 List of Active Health Facilities by Province and District. April 13, 2009. Health Management Information System [HMIS], Planning Directorate, DG Provincial Public Health.


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Initially, the North-West University Laboratory in South Africa was chosen as the parallel testing facility but because FEDEX could not transit medicines to South Africa through their center in Dubai, and DHL was closed indefinitely, an alternative secondary laboratory was selected. Based on past experience with the Supply Chain Management System (SCMS) project, a USAID-funded supply project for antiretroviral medicines, ZL in Germany was selected. Training for Field Sample Collectors Most field sample collectors had in-depth technical knowledge of the medicines supply in Afghanistan. Each field sample collector received training on the theoretical and practical aspects of the survey methodology to ensure common understanding and consistency in the field work. The process of selecting samples, cross-checking samples, communicating with the center, packing, labeling and transporting the samples was thoroughly discussed and the various tools and forms for sample and data collection were explained in detail. The training activity included practical sampling, data collection and role plays. Processes and tools were improved as a result of observations and discussions with all participants. Collection of Medicines for Analytical Testing In accordance with analytical laboratory requirements, a set of 100 units of each oral dosage form (tablets and capsules) was collected as a sample. Each sample of injection and powder forms was comprised of 10 units (Table 1). Each sample was clearly distinguished for the analytical laboratory testing—same batch/lot number, from the same manufacturer and of the same expiry date. All samples were collected simultaneously from across the country in September 2009. Some samples were randomly selected for analytical testing in the secondary laboratory. For the purpose of avoiding duplication during field visits, a supervisor located at a central point in Kabul actively collated all the vital information on the major characteristics (i.e. batch/lot number, manufacturer and country of origin and expiry date) of the medicines and directed field sample collectors accordingly. Before a sample was collected, the field sample collectors called a designated telephone number staffed by a supervisor with knowledge of sample batch/lot number-manufacturer-expiry date matching, learned from the field data collection training sessions. The batch/lot number, manufacturer and expiry date of the prospective sample were given. Upon verification from already collected and documented batch/lot numbers, the sample collector was directed to randomly collect the sample if the batch/lot number did not constitute duplication. Duplicates were rejected. A field sample collection validation tool was developed and used for this purpose (Table 2).


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Table 1. Total number of units per sample collected for laboratory testing in January 2010 Medicine

Total Samples Collected

Total Units per Medicine

Comment

Amoxicillin Capsule/Tablet

39 3,900 100 units per sample.

Omeprazole Capsule 25 2,500 100 units per sample. Alprazolam Tablet 24 2,400 100 units per sample. Atenolol Tablet

30 + 30

6,000

100 units per sample, but 200 units were collected from each selected health facility because of split sampling for parallel analytical testing. Out of the additional units, some samples were randomly selected for analytical testing in the secondary laboratory.

Levonorgestrel/Ethinyl Estradiol Tablet

39 + 39

7,800


Paracetamol Tablet 36 3,600 100 units per sample. Ciprofloxacin Tablet 25 2,500 100 units per sample. Ceftriaxone Injection 26 260 10 units per sample. Gentamicin Injection 35 350 10 units per sample. Medroxyprogesterone Acetate Depot Injection

23

230

10 units per sample.

Oral Rehydration Salt Powder

46 + 46

920


Table 2. Field sample validation tool Field Sample Collection Validation Tool

Name of Medicine

No Name of Site

Category Vital Information Zone Batch/Lot

Number Manufacturer Expiry

Date Comment


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Samples of all 11 medicines were collected from both the public and private-for-profit sectors. These medicines are all authorized for sale in the selected private health facilities. A total of 169 (49 percent) samples were collected from the private-for-profit sector—84 (24 percent) samples from private hospitals and 85 (24.5 percent) samples from private pharmacies (Figure 1). A total of 179 (51 percent) samples were collected from the public sector—24 (6.9 percent) samples from specialty/provincial/regional hospitals, 13 (3.7 percent) samples from district hospitals, 76 (21.9 percent) samples from CHCs and 66 (19 percent) samples from BHCs. Amongst the donor-supported public health facilities, the highest percentage (18 percent) of samples was collected from USAID-supported facilities. Thirty-one (9 percent) samples were collected from public health facilities with no donor support and 8 (2.3 percent) samples were collected from public health facilities supported by other donors. In the public sector, all samples of Alprazolam, Atenolol, Ciprofloxacin and Ceftriaxone were collected from specialty/provincial/regional and district hospitals because these were available at this level of care only. The samples of the other seven medicines were collected from the CHC and BHC facilities, where these were available as per national policy.

Figure 1. Distribution of samples collected and tested by sector and donor-support Out of a target of 464 samples, a total of 348 (75 percent) were successfully collected and tested in the primary laboratory. An additional 115 samples of Atenolol 50mg or 100 mg, Levonorgestrel/Ethinyl Estradiol 0.25/0.05 mg or 0.30/0.03 mg, and ORS were collected for parallel testing as an assessment of reliability of the primary laboratory results. For cost reasons, 48 samples were randomly and proportionally selected from the 115 samples and tested at the secondary laboratory (Table 3).


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Table 3. Samples collected from selected sites in the provinces for laboratory analytical testing in January 2010 Number of Samples by Sites Medicine PrH PrPh Public (USAID- group) Public (WB- and EU- group) Total

SH/PH/RH

DH CHC BHC SH/PH/RH

DH CHC BHC

Amoxicillin 250 mg or 500 mg Capsule

8 8 0 0 5 4 0 0 8 6 39

Omeprazole 20 mg Capsule

8 8 3 1 0 0 3 2 0 0 25

Alprazolam 0.5 mg Tablet

8 8 2 1 0 0 3 2 0 0 24

aAtenolol 50 mg or 100 mg Tablet

8 8 0 0 1 1 0 0 7 5 30

aLevonorgestrel/Ethinyl Estradiol 0.25/0.05 mg or 0.30/0.03 mg Tablet

8 8 0 0 4 5 0 0 8 6 39

Paracetamol 500 mg Tablet

8 8 0 0 3 3 0 0 7 7 36

Ciprofloxacin 500 mg Tablet

8 8 3 1 0 0 3 2 0 0 25

Ceftriaxone 0.5/1 g Injection

8 8 4 1 0 0 3 2 0 0 26

Gentamicin 40 mg or 80 mg Injection

8 8 0 0 4 3 0 0 7 5 35

Medroxyprogesterone Acetate Depot 150 mg/ml Injection

4 5 0 0 3 2 0 0 7 2 23

aOral Rehydration Salt Powder

8 8 0 0 8 8 0 0 7 7 46

Total samples 84 85 12 4 28 26 12 8 51 38 348 aParallel analytical testing at ZL, Germany As seen in Table 4, the key identifier for differentiation was the batch number. The golden rule was to collect each sample set made up of units of medicines which had the same batch/lot number, manufacturer and country of origin and expiry date. Any other set of samples collected must have clearly distinctive characteristics from an already collected sample. All samples collected had at least three months shelf life remaining. The set of units must be of different batch/lot numbers, or manufacturer, or expiry date from any other set. Products which had the same batch/lot number, manufacturer or expiry date, but different countries of origin were considered as different samples, because conditions of manufacturing practice could differ, and either of them can be an imitation.


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Table 4. Permutation diagram for sample collection in January 2010 Permutation of Samples (Developed by the QA External Consultant) Sample Batch/Lot number Manufacturer Expiry date

Same Different Same Different Same Different

Set 1 AAA 123 ABCD Jan 2010 Set 2 AAA 123 ABCD May 2011 Set 3 AAA 123 EFGH Jan 2010 Set 4 AAA 123 EFGI May 2012 Set 5 BBB 456 ABCD Jan 2010 Set 6 BBB 457 ABCD May 2013 Set 7 BBB 458 EFGJ Jan 2010 Set 8 BBB 459 EFGK May 2014

Coding of Samples Considering the fact that the primary laboratory was located in the sub-region of most countries of origin of the medicines collected, measures were taken to avoid bias. Samples were removed from their original jackets and coded to blind not only the primary laboratory, but also the secondary, for consistency (Table 5). Each code consisted of five digits: the first digit was a letter, representing the province; the second digit was a number, representing the type of facility; and the third, fourth and fifth digits were letters, representing the first three letters of each medicine. The codes were written clearly on each sample pack in a uniform handwriting, to ensure consistency. In addition to the codes, the complete names and dosage forms of the samples were stated on the packages. Table 5. Coding system for sample collected and tested in January 2010 Province Code Type of HF Code Medicine Code Heart A PrH 1 Amoxicillin AMO Badakhshan B PrPh 2 Omeprazole OME Baghlan C SH/RH/PH 3 Alprazolam ALP Kandahar D DH 4 Atenolol ATE Khost E CHC1 5 Levonorgestrel/Ethinyl Estradiol LEV Kabul F CHC2 6 Paracetamol PAR Balkh G BHC1 7 Ciprofloxacin CIP Nangarhar H BHC2 8 Ceftriaxone CEF NA NA NA NA Gentamicin GEN NA NA NA NA Medroxyprogesterone Acetate

Depot MED

NA NA NA NA Oral Rehydration Salt ORS Packaging and Labeling The samples were placed in sealed zip lock plastic bags for transportation to the laboratories. The samples were grouped accordingly and placed in individual boxes and sealed by a joint team from the GDPA and SPS after which the sealed boxes were signed by the GDPA officials. The plastic zip bags were labeled in accordance with SCMS specifications and minimum information


24

such as the name of the medicine, dose and number of units collected was stated. For the purpose of blinding the laboratories to avoid bias, the batch/lot number, name of manufacturer, expiry date and country of origin were omitted on the labels. All these characteristics, together with information on the collection location, type of health facility, name of person supplying the sample, and name of person collecting the sample were secured in a data base at the MSH and GDPA offices. The labels were boldly printed in indelible ink and affixed to the boxes as required by the freight companies and customs. Some samples of Levonorgestrel/Ethinyl Estradiol tablets submitted for parallel testing at the secondary laboratory were labeled to contain Levonorgestrel 0.150 mg and Ethinyl Estradiol 0.03 mg, which should have been labeled Levonorgestrel 0.30 mg and Ethinyl Estradiol 0.03 mg. This was cross-checked from the original hard copies and electronic database as well as the retained jackets, and the necessary corrections were completed. The results were then reconciled with the results from the primary laboratory by an expert in medicines analytical testing. Laboratory Testing All the medicines were tested in a primary laboratory, Vimta Labs Ltd., a WHO-accredited laboratory in Hyderabad, India. This laboratory was chosen based on its track record, experience with the SCMS project and affordable cost. The tests were performed in accordance with established pharmacopeial standards—United States Pharmacopeia (USP) and the International Pharmacopeia (Ph. Int.). The product quality attributes addressed in the sampling and testing survey were in accordance with the USP for all the medicines, and Ph. Int. for ORS at the laboratories (Annex E). Selected Laboratories The primary laboratory, Vimta Labs Ltd., is a large contract testing, research and development laboratory in India, and is both WHO and ISO 170125 accredited. Established in 1984, Vimta Labs, Ltd. has a team of 640 professionals comprising 466 scientists in various disciplines such as chemistry, pharmaceuticals, medicine, microbiology, molecular biology and informatics. Vimta Labs Ltd. has capacity to conduct analyses according to the most current edition of the internationally established pharmacopeias, including the USP, the British Pharmacopoeia, the European Pharmacopoeia, and the Ph. Int.15 The secondary laboratory, Zentral Laboratorium (ZL) in Germany, is ISO 17025 and WHO- accredited central laboratory of the German Pharmacists Association. Its areas of specialty include the characterization of materials, auxiliary materials and finished medicinal products and biopharmaceutical/pharmacokinetic studies of medicines. The ZL leads clinical trials of phases I and IV. The ZL maintains in many areas, close cooperation with renowned scientists and institutions, such as the United States Food and Drug Administration. 16

15 www.vimta.com/html/contactus.html 16 http://www.zentrallabor.com


25

Ariana Afghan Airlines flew the samples non-stop from Kabul to Delhi, where Vimta Labs, Ltd. collected the samples. Safi Airlines flew the samples non-stop from Kabul to Frankfurt for customs clearance. Storage and Transportation of Samples All medicines collected were temporarily kept at room temperature in their original conditions and in accordance with good storage practice and manufacturer’s recommendations. . The samples were stored for less than three months at the Tech Serve medicines warehouse in Kabul. Fragile medicines, especially the injections, were carefully wrapped in cushions and bubbles wrap and taped to ensure that they were well protected before placing them in zip-lock bags. Commercial invoices were clearly and accurately prepared to avoid problems with your shipment. All requirements were met as prescribed by the SCMS. The medicines were transported under specified storage conditions and in sealed boxes. The laboratories duly acknowledged receipt of the samples in good conditions. Data Entry and Analysis Results of analytical testing received from the primary and secondary laboratories were received in January 2010 and April 2010, respectively, and immediately entered into Microsoft Excel 2007. Data were double entered in distinct spreadsheets by separate individuals, to minimize human error. The data were then cross-checked for accuracy and consistency by the lead consultant and other team members. Data were examined, analyzed, and computed into percentages as appropriate, with assistance from experts in the field. Where necessary and appropriate, data were tabulated and presented in graphs for better presentation purposes.


26

RESULTS OF MEDICINES SAMPLING AND TESTING Countries of Origin and Manufacturers In this survey, the medicines collected and analyzed came from twenty different (20) countries (Figure 2). Based on the survey, the largest suppliers of medicines in Afghanistan were Pakistan (24 percent), India (20 percent), Iran (17 percent) and China (11 percent). The other sixteen countries (28 percent) included the United States, Germany, and Belgium.

Figure 2. Countries of origin of medicines collected and tested in January 2010

A total of 145 manufacturers were represented in the samples collected (Annex F). The numbers of samples collected from the major manufacturing companies are: 18 from Exir, 15 from Wyeth, 12 from Medicamen Biotech, 11 from Davis pharmaceutical, 10 from Gland Pharma and 9 from Merck. Findings of Analytical Testing Table 6 provides laboratory analytical testing details on particular medicines. Of 348 medicines collected and tested in the laboratory, 315 (91 percent) passed and 33 (9 percent) failed to meet USP and Ph. Intl. standards. All 25 samples of Omeprazole capsule, 35 of Gentamicin injection and 46 of ORS fully met the standards. Approximately 43 percent of Medroxyprogesterone Acetate injections 150 mg/ml and 29 percent of Alprazolam tablets 0.5 mg failed to meet international standards. Table 6. Results of laboratory analytical testing of medicines in January 2010 Medicine Target Collected Passed Passed (%) Failed Failed (%) Amoxicillin 48 39 37 95 2 5 Omeprazole 32 25 25 100 0 0 Alprazolam 32 24 17 71 7 29 Atenolol 48 30 27 90 3 10 Levonorgestrel/Ethinyl Estradiol 48 39 37 95 2 5 Paracetamol 48 36 30 83 6 17 Ciprofloxacin 32 25 23 92 2 8 Ceftriaxone 32 26 25 96 1 4 Gentamicin 48 35 35 100 0 0 Medroxyprogesterone Acetate 48 23 13 57 10 43 Oral Rehydration Salt 48 46 46 100 0 0 Total 464 348 315 91 33 9


27

Passed Samples Out of the 315 samples that passed laboratory analytical testing, 160 samples (51 percent) were from the public sector and 155 samples (49 percent) were from the private sector. The 155 passed samples represent 92 percent of all samples collected and tested from the private sector. Seventy-eight out of 84 samples (93 percent) collected from private hospitals passed and out of 85 samples collected from private pharmacies, 77 (91 percent) samples passed the test (Table 7). Table 7. Samples passing laboratory analytical testing by sector and donor support Donor Type Collected Passed Passed (%)

MoPH/WB 41 35 85 MoPH/EU 36 32 89 MoPH/USAID 63 56 89 MoPH 31 29 94 MoPH/Others 8 8 100 Public Sector 179 160 89 Private Hospital 84 78 93 Private Pharmacy 85 77 91 Private Sector 169 155 92 Total 348 315 91

In the public sector, the 160 passed samples represent 89 percent of all medicines collected and tested from public health facilities. Fifty-six out of 63 samples (89 percent) collected from USAID-supported public health facilities passed analytical test. Out of 41 samples collected from WB-supported and 36 samples collected from EU-supported public health facilities,35 (85 percent) and 32 (89 percent) samples, respectively, met test requirements. Samples collected from donor-supported public health facilities were not confirmed products supplied by the respective donors. Twenty-two out of 24 samples (92 percent) and 61 out of 66 samples (92 percent) collected from SH/PH/RHs and BHCs respectively passed the test (Figure 3). District hospitals recorded the lowest percentage, with 10 (77 percent) out of 13 samples passing the test.

Figure 3. Distribution of samples passing analytical testing by health facility


28

Failed Samples Out of the 33(9 percent) samples that failed laboratory analytical testing, 14 samples were from the private sector and 19 samples were from the public sector. The 14 failed samples represent 8 percent of all samples collected and tested from the private sector. Six out of 84 (7 percent) samples collected from private hospitals failed to meet standards. Out of 85 samples collected from private pharmacies, 8 (9 percent) failed the test (Table 8). Table 8. Samples failing laboratory analytical testing by sector and donor support Donor Type Collected Failed Failed (%) MoPH/WB 41 6 15 MoPH/EU 36 4 11 MoPH/USAID 63 7 11 MoPH 31 2 6 MoPH/Others 8 0 0 Public Sector 179 19 11 Private Hospital 84 6 7 Private Pharmacy 85 8 9 Private Sector 169 14 8 Total 348 33 9

In the public sector, the 19 failed samples represent 11 percent of all medicines collected and tested from public health facilities. Seven out of 63 (11 percent) samples collected from USAID-supported public health facilities failed analytical testing. Out of 41 and 36 samples collected from WB-supported and EU-supported public health facilities respectively, 6 (15 percent) and 4 (11 percent) failed. Samples collected from donor-supported facilities were not confirmed products supplied by the respective donors. Two (8 percent) out of 24 samples and 5 (8 percent) out of 66 samples collected from SH/PH/RHs and BHCs respectively failed the test (Figure 4). District hospitals recorded the highest percentage, with 3 (23 percent) out of 13 samples failing.

Figure 4. Distribution of samples failing analytical testing by health facility


29

Findings of Analytical Testing by Province, Manufacturer and Country Figure 5 shows the distribution of failed samples by province. Of the 33 failed samples, Balkh Province (19 percent) and Nangarhar Province (18 percent) had the highest numbers of failed products, followed by Herat Province (15 percent). Kandahar Province (6 percent) had the least percentage of failed products. Surprisingly, the capital city, Kabul, was relatively low (9 percent) in numbers of sampled medicines that failed. This could be a possible indication of the need to focus more attention on the rural deprived areas of the country, which can serve as fertile ground for the distribution of low quality medicines.

Figure 5. Distribution of failed samples by provinces by number and percentage Eleven countries of origin accounted for the 33 failed products (Figure 6). The majority of the failed products come from five countries: India (22 percent), followed by Pakistan (19 percent), Holland (16 percent), China (13 percent), and Belgium (12 percent).

Figure 6. Percentages of failed samples by country of origin


30

Table 9 lists the 22 manufacturing companies whose products constitute the 33 samples that failed to meet pharmacopeial standards. Of the samples collected from Exir (18 samples), Wyeth (15 samples), and Merck (9 samples), one sample each failed the test. Eighteen other manufacturers each had one product that failed the analytical test. Royal International (100 percent), Organon (71 percent), Pfizer (50 percent) and Nabi Qasem (50 percent) had the highest percentages of failed samples. Table 9. List of manufacturing companies of failed samples in January 2010

Manufacturer Number of samples collected

Number of failed samples

Exir (Iran) 18 1 Wyeth (Canada) 15 1 Merck (Pakistan) 9 1 Pfizer (Belgium) 8 4 Schering (Germany) 8 1 Shijiazhuang (China) 8 1 Organon (Holland) 7 5 Nabi Qasem (Pakistan) 4 2 Royal International (India) 4 4 Marlex (USA) 3 1 IRZA (Indonesia) 2 1 Saviour Bentic (India) 2 1 Amir Pharma (Pakistan) 1 1 Astra (India) 1 1 Blenax (Turkey) 1 1 Jackson Labs (India) 1 1 Jiamsu Pengygo (China) 1 1 Julphar (UAE) 1 1 Ningbo (China) 1 1 Shanghi (China) 1 1 Stinly (Pakistan) 1 1 Unitic Pharmaceutical (Pakistan) 1 1 Total 98 33 Findings of Analytical Testing by Individual Medicines Amoxicillin: Thirty-nine samples of Amoxicillin 500 mg (37 samples) and 250 mg capsules (2 samples) were collected. These were tested for identification, weight variation, disintegration and assay as per USP-32. Out of 39 samples tested, 37 (95 percent) passed but 2 (5 percent) failed the requirements for assay. In addition to failing the assay test, one failed the dosage uniformity test as well. One failed sample was collected from a private pharmacy in Khost Province and the other from a BHC, also in Khost Province (Figure 7).


31

Omeprazole: Twenty-five samples of Omeprazole 20 mg capsules were collected and tested for identification, assay, dosage uniformity and dissolution as per USP-32. All samples passed the test. Three samples were border line on meeting dosage uniformity requirements. Alprazolam: Twenty-four samples of Alprazolam 0.5 mg tablets were collected and tested for identification, assay and dissolution as per USP-32. Out of 24 samples tested, 17 (71 percent) passed but 7 (29 percent) failed the pharmacopeial standards. Five failed to meet 90 percent minimum assay and 80 percent dissolution. One failed to meet 80 percent dissolution and another failed to meet 90 percent assay. The samples that failed were collected from a private hospital at Khost, two private pharmacies in Kabul and Nangarhar Provinces, the regional hospital in Balkh Province, the provincial hospital in Nangarhar Province, and two district hospitals in Balkh Province (1) and Nangarhar Provinces. Atenolol: Thirty samples of Atenolol 50 mg tablets (20 samples) and 100 mg (10 samples) were collected. These were tested for identification, assay, and dissolution as per USP-32. Out of the 30 samples tested, 27 (90 percent) passed but 3 (10 percent) failed the standards for assay and dissolution. Two samples failed dissolution and one failed to meet assay standards. Two of the failed samples were collected from private hospitals at Takhar Province and Balkh Province. The remaining failed sample was collected from a CHC in Nangarhar Province. The sample representing the private hospital in Badakhshan Province was collected from neighboring Takhar Province as an alternative because there are no private hospitals in Badakhshan. Levonorgestrel/Ethinyl Estradiol: Thirty-nine samples of Levonorgestrel/Ethinyl Estradiol 0.25 mg tablets /0.05 mg or 0.30/0.03 mg were collected and tested for dissolution, assay, and uniformity of dosage for Levonorgestrel and Ethinyl Estradiol separately, in accordance with USP-32. Out of 39 samples tested, 37 (95 percent) passed but 2 (5 percent) failed the standards for assay and dosage uniformity. One was very low on Levonorgestrel and Ethinyl Estradiol and failed all attributes. The second sample failed to meet Levonorgestrel assay. Both failed samples were collected from a CHC and a BHC in Baghlan Province. Paracetamol: Thirty-six samples of Paracetamol 500 mg tablets were collected and tested for identification, weight variation, disintegration and assay as per USP-32. Out of 36 samples tested, 30 (83 percent) passed but 6 (17 percent) failed to meet standards for assay. Five (5) samples failed the 90 percent assay limit and the other one failed the 110 percent assay limit. The latter was a possible laboratory issue, as the average tablet weight was less than the assay value. The 6 failed samples were collected from a private hospital at Takhar Province, two private pharmacies in Badakhshan and Kandahar Provinces, two CHCs in Kabul and Balkh Provinces, and a BHC in Kandahar Province. Ciprofloxacin: Twenty-five samples of Ciprofloxacin 250 mg tablets (1 sample) and 500 mg tablets (24 samples) were collected and tested for identification, weight variation, assay, and disintegration according to USP-32. Out of 25 samples tested, 23 (92 percent) passed but 2 (8 percent) exceeded the 110 percent assay limit. Of the two samples that failed, one sample significantly exceeded the assay limits and the other marginally failed to meet the limit. This could be a laboratory issue, acceptable within analytical errors. The differences between the two


32

tests readings respectively were too large. One sample was collected from a private hospital in Nangarhar Province and other was collected from a district hospital in Herat Province. Ceftriaxone: Twenty-six samples of Ceftriaxone 0.5/1 g injection were collected and tested for identification, assay, pH, sterility, and bacterial endotoxins in accordance with USP-32. With the exception of one which was Ceftriaxone 0.5 g injection, all the samples were Ceftriaxone 1 g injection. Out of 26 samples tested, 25 (96 percent) passed and only 1 (4 percent) failed assay and pH requirements. The sample contained less than 2 percent of the declared amount. This product, from a private pharmacy in Baghlan Province might be dangerous because the contents were unknown. Gentamicin: Thirty-five samples of Gentamicin 40 mg injection (3 samples) and 80 mg injection (32 samples) were collected and tested for identification, assay, pH, and bacterial endotoxins in accordance with USP-32. None (0 percent) failed—all met requirements. Medroxyprogesterone Acetate: Twenty-three samples of Medroxyprogesterone Acetate Depot 150 mg/ml injection were collected and tested for identification, assay, pH, sterility, and bacterial endotoxins in accordance with USP-32. Out of 23 samples tested, 13 (57 percent) passed but 10 (43 percent) failed to meet the maximum and minimum assay standards. Nine samples failed to meet minimum assay standards (67-84 percent limit of 90 percent) and one exceeded the assay limit (113 percent of limit 110 percent). The 10 failed samples were collected from one private hospital in Baghlan Province; two private pharmacies at Herat Province and Kabul Province; five CHCs - two each in Herat and Balkh Provinces and one in Khost Province; and two BHCs, one each in Herat and Nangarhar Provinces. Oral Rehydration Salt: Forty-six samples of Oral Rehydration Salt powder were collected and tested for identification and assay as per Ph. Int. standards. The identification and assay testing were completed for the combined product and individual components (sodium, potassium, chlorides, citrate, and glucose). None (0 percent) failed. All 46 (100 percent) samples met standards at the primary and secondary laboratories.

Figure 7. Results of individual medicines collected and tested in January 2010


33

DISCUSSION Source of Failed Samples Samples that failed testing were found in all subsectors (public, donor-supported, and private facilities). However, given the lack of public trust in the quality of medicines in the private sector, it was surprising to find that only 6 percent of samples collected in private pharmacies failed monograph testing. This may be due to sample collection being limited to major towns and cities and not rural and remote areas and the focus on key essential medicines. This does not exclude the possibility that a larger proportion of substandard or even counterfeit medicines are not included in Afghanistan’s Licensed Drug List (LDL) or registered with the GDPA and are circulating in the country. Anecdotal information from local experts and the generalized perception is that there are thousands of non-registered products circulating in the market, many sold by non-licensed (informal) medicine sellers. Still, an overall average of 9 percent failure rate for samples collected in both public and private sectors is not satisfactory, and measures are needed to further reduce this. If this situation represents the “tip of the iceberg”, it is reasonable to assume that the problem may be larger in areas where medicines regulatory enforcement through effective inspections and sampling for testing is insufficient and non-registered products are widely available. Nature of Test Failures and Potential Solutions Non-compliance with assay requirements was the overwhelming reason for sample test failures. Not meeting dissolution test requirements was also important with eight samples that failed the test. Failing to meet minimum assay threshold amounts by significant differences may be detected using a simple and relative inexpensive method, such as thin-layer chromatography (TLC), for up to 55 essential medicines. TLC is one of the methods included in the German Pharma Health Fund (GPHF) Minilab® kit. Currently the Minilab ® contains TLC methods for 37 medicines in the LDL. There are unofficial TLC methods developed by the United States Food and Drug Administration’s Division of Testing and Applied Analytical Development. The described methods may cover an additional 32 medicines in the LDL. Tables 10 and 11 in Annex G identify the active ingredients of medicines in the LDL and the Essential Drug List (EDL) that have available TLC methods for rapid screening for quality and detection of counterfeit products. Additional TLC methods could be developed and validated or tested locally or may be developed in collaboration with academic institutions in other countries that are also using the Minilab® to progressively expand the coverage of medicinal products through this testing method. The GPHF Minilab® Testing The GPHF Minilab® is a mobile mini-laboratory contained in two suitcase-sized containers. The materials are used in a step-by-step procedure that starts with inspecting the product for labeling and physical attributes. If this passes requirements, the medicine is tested for dissolution/disintegration. If it passes this test, then a color reaction test is done to confirm the


34

chemical identity of the product. The last step is to determine if the content is within an accepted amount by testing with a thin-layer chromatography method. Because there is no need to proceed to the next step if a product fails any step, the GPHF Minilab® It is practical, fast and efficient and eliminates the need for unnecessary testing. Process of Assuring the Quality of Medicines Assuring the quality of medicines begins with the initial evaluation of a medicine’s efficacy, safety and other criteria prior to its inclusion in the LDL and EDL. When interested suppliers apply to register and import products listed in the LDL, the MoPH GDPA evaluates the documents (and samples) submitted by the suppliers and, if they meet requirements, the directorate registers the product and allows its importation or local production. Because the EDL, LDL and the product registration provide the first indication that a product meets quality standards, only registered medicines should be allowed and sold in the market. Effective enforcement of registration and the removal of non-registered products is the first step to keeping a substantial proportion of substandard and fake or counterfeit medicines out of the market. Inspection of import shipments is the next line of defense against substandard and fake or counterfeit medicines. The major ports of entry for imported medicines are at border crossings located in Nangarhar, Kandahar, Herat, Balkh, Khost and Nimruz Provinces. Shipments undergo customs inspection and reportedly, samples are taken by GDPA sampling officers in Kabul, Nangarhar and other provinces and are sent to the Food and Drug Quality Control Laboratory (FDQCL) in Kabul for analysis. The process may take as long as 30 days before the shipments are released and continue to the importers’ storage locations. Establishing rapid screening and testing at these points of entry into Afghanistan is a second line of defense against substandard and fake and possibly counterfeit medicines. The use of GPHF Minilab® screening and testing with explicit and well-defined criteria based on risk for substandard quality and decision-making to approve onward passage may be an effective and efficient approach to accelerate the process; and medicine importers are likely to support such an approach. Further inspection of NGOs’, wholesalers’ and distributors’ warehouses may detect non-registered products or storage conditions that may contribute to deterioration of product quality. If appropriate, samples could be collected for rapid testing or more sophisticated testing at the FDQCL. Inspection of the three types of private pharmacies for detection of non-registered medicines can be also conducted using a step-wise way. This allows time for the MoPH to develop its capacity to enforce compliance with medicines registration, while the private sector has time to prepare and effectively submit applications for medicines registration over a reasonable period of time before strict enforcement of registration takes place. At the appropriately designated time all non-registered medicines should be confiscated and destroyed, which may result in potentially significant financial losses to medicines importers and wholesalers if their products are not registered, although many or some of the non-registered medicines may be quality products. Therefore, suppliers would have an incentive to follow the established regulatory process. If appropriate, and according to well-defined criteria, samples could be taken for random testing to verify that they meet quality standards.


35

Another important component of a national quality assurance strategy is product problem reporting by both health care providers and the general public. Such a program would include media messages to the community with simple tips to detect or prevent medicine quality problems and to report them to the competent authorities. The program would include appropriate tools, reporting and communication mechanisms. The development of such a strategy will require effective stakeholder engagement and consensus. Key stakeholders include the National Medicines and Food Board (NMFB), the GDPA, the FDQCL, Legislation Implementation Ensuring Directorate (LIED) of the MoPH, the Afghanistan Medicine Services Union (Medicines Sellers Association, Medicine and Medical Equipment Importers Association and Pharmaceutical Manufacturers Association), Pharmacists Association, Physicians Association, Provincial Public Health Directorates, Ministry of Finance, Customs Offices, among others. The current ad hoc GDPA Quality Assurance Task Force could be constituted as a technical committee supporting the NMFB. An appropriate analysis of resources (physical space, location, people, and the associated costs) is needed to determine the convenience and suitability of expanding screening and rapid detection of substandard, fake or counterfeit medicines with the GPHF Minilab® approach.


36

CONCLUSION Substandard products are found in both the public (government and donor-supported) and the private (for-profit) sectors. Findings relate primarily to the better regulated segment of the Afghanistan pharmaceutical market but measures are still needed to reduce the observed 9 percent test failure rate. A comprehensive but realistic and sustainable strategy is needed to assure the quality of medicines in Afghanistan.


37

RECOMMENDATIONS 1. The GDPA and the FDQCL should conduct a feasibility analysis, including cost and

financing implications, for implementing a sustainable risk-based medicines quality screening program, which will inform the MoPH and the NMFB towards the development of a national quality assurance program.

2. The MoPH should develop a national strategy for medicines quality assurance, which should include:

a. registration of medicines products before they can be manufactured, imported or sold; b. inspection and enforcement of registration status, allowing only registered products in

the market (wholesalers, retail pharmacies and other medicine shops); c. risk-based sampling and screening with the GPHF Minilab® for a number of

medicines (major ports of entry or regional locations, wholesalers, retail pharmacies and other medicine shops);

d. confirmatory testing with legal pharmacopeial reference methods at the FDQCL when appropriate or when GPHF Minilab® and TLC rapid methods are not available; and

e. product problem reporting by healthcare providers and the community.

3. The national strategy for medicines quality assurance should include appropriate actions in the public, the NGO and the private for-profit sectors, and have broad stakeholder consensus and support. The NMFB is the appropriate advisory and coordinating body to support the MoPH to oversee this strategy.


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ANNEX A. NAMES AND AGENCIES OF SAMPLE COLLECTION TEAM MEMBERS Name Title Organization Yusuf Inua QA Consultant MSH/SPS Mohammad Zafar Omari Country Team Leader MSH/SPS-Kabul Afghanistan Wahidullah Karwar QA Advisor MSH/SPS-Kabul Afghanistan Abdul Zahir Siddiqui RMU Advisor MSH/SPS-Kabul Afghanistan Abdul Tawab Khetab Procurement Advisor MSH/SPS-Kabul Afghanistan Lotfullah Ehsas RMU Officer MSH/SPS-Kabul Afghanistan Kamila Sultani Director of Food and Drug Labs MoPH

Khalil Khakzad GDPA/MoPH Activities Coordinator MoPH/GDPA

Zekria Fatehzada

Supervision and Evaluation Manager

MoPH/GDPA

Shaperi Pharmacist MoPH/GDPA/API Salih Mohammad Pharmacist MoPH/GDPA Mohibullah Pharmacist MoPH/GDPA/API Abdul Rahim Pharmacist Mohmmd Sabir Pharmacist MoPH/GDPA Mahmood Pharmacist MoPH/GDPA Nazir Ahmad Planning Manager MoPH/GDPA Merza Mohammad Ayoobi

Deputy Director of Pharmaceutical Enterprise

MoPH/GDPA

Nasir Pharmacist MoPH/GDPA Said Razashah Masomi

Manager of Pharmaceutical Establishment Department

MoPH/GDPA

Khalil Pharmacist MoPH/GDPA/API Belal Ahmad Pharmacist MoPH/GDPA/API Dawod Shah

Deputy Manager for Procurement and Registration

MoPH/GDPA/API

Mohammad Zarif

Manager of Narcotic and Psychotropic Medicines Department

MoPH/GDPA

Samiullah Pharmacist MoPH/GDPA Ishaq Pharmacist MoPH/QC Labs Mohammad Zaman Pharmacist MoPH/QC Labs Abdul Hadi Pharmacist MoPH/GDPA Abdul. Basir Pharmacist MoPH/QC Labs Nangialai Pharmacist MoPH/GDPA Nazir Ahmad Pharmacist MoPH/GDPA Nasir Ahmad

Pharmacist

Nangarhar Provincial Health Directorate

Ezatullah Pharmacist MoPH/GDPA Abdul Zahid Pharmacist MoPH/GDPA/API Mohammad Monir Pharmacist MoPH/GDPA/API Karimullah

Pharmacist

Khost Provincial Health Directorate

Said Sharif Pharmacist MoPH/GDPA Sabrulhaq Sampling Manager MoPH/GDPA Nasim Pharmacist MoPH/GDPA Ajmal Pharmacist MoPH/GDPA Hashmat Pharmacist MoPH/GDPA


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Name Title Organization Zabiullah Pharmacist MoPH/GDPA Mohammad Naser Pharmacist MoPH/GDPA/API Abdullah Pharmacist MoPH/GDPA Ghulam Qader

Pharmacist

Balkh Provincial Health Directorate

Hamidullah Pharmacist MoPH/GDPA Khalilullah Pharmacist MoPH/GDPA Haji Dor Mohammad

Pharmacist

Kandahar Provincial Health Directorate

Aziz Ahmad Pharmacist MoPH/GDPA Hedaytullah Pharmacist MoPH/GDPA Said Mohammad Sajadi Pharmacist MoPH/GDPA/API Amir Mohammad

Pharmacist

Baghlan Provincial Health Directorate

Nasir Ahmad Pharmacist MoPH/GDPA Shabir Ahmad Pharmacist MoPH/GDPA Najmudin

Pharmacist

Badakhshan Provincial Health Directorate

Ghulam Omar Pharmacist MoPH/GDPA Shakila Pharmacist MoPH/GDPA/API Karima Pharmacist MoPH/GDPA/API

Mohammad Asif

Pharmacist

Herat Provincial Health Directorate


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ANNEX B. AFGHANISTAN DEMOGRAPHIC DATA Item Value Source Total Area 652,864 km². Central Statistics

Organization (CSO) Number of Provinces 34 CSO Number of Districts 354 CSO Total Population—October 2009 25.5 million CSO Urban Population 5.5 million (22.9 %) CSO Rural Population 18.5 million (77.1 %) CSO Migrant Population 1.5 million CSO Life Expectancy— Males and Females 44 years CSO Literacy Rate (National Survey 2007) 26 % CSO Gross Domestic Product Per Capita – 2008 USD426 CSO Infant Mortality Rate (Per 1000 Live Births) 111/1,000 MoPH/HMIS Maternal Mortality Rate (Per 100,000) 1,400/100,000 MoPH/HMIS Total Annual Government Health Expenditure USD162 million MoPH/HMIS Total Annual Value of International Aid to Health Sector (2009) USD135 million MoPH/HMIS

Real Growth Rate (2007 Est.) 7.5 % CSO Inflation Rate (2005 Est.) 16.3 % Unemployment Rate (2005 Est.). 40 % CSO Number of Special Hospitals 22 MoPH/HMIS Number of Provincial Hospitals 30 MoPH/HMIS Number of Regional Hospitals 5 MoPH/HMIS Number of District Hospitals 60 MoPH/HMIS Number of Comprehensive Health Centers (CHC) 372 MoPH/HMIS Number of Basic Health Centers (BHC) 779 MoPH/HMIS Number of Private Hospitals 174 MoPH/HMIS Number of Sub Health Centers 305 MoPH/HMIS Number of Mobile Clinics 47 MoPH/HMIS Number of Other Facilities 79 MoPH/HMIS


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ANNEX C. NATIONAL CONSUMPTION AND COST OF SELECTED MEDICINES FOR ANALYTICAL TESTING Islamic Republic of Afghanistan

Ministry of Public Health General Directorate of Pharmaceutical Affairs Pharmaceutical Planning Department

National Annual Consumption and Estimated Value of Each Medicine (only for those imported medicines which followed the official and legal channel)

The table cover the Private and Public Sector (NGOs and Private Import Except MoD, MoI and National Security) Date: 1387 (20 March 2008-19 March 2009)

Medicine Name

Form

Requested quantity of medicine approved by the GDPA for importation from foreign countries

Total cost in USD

Atenolol tablet 22,309,200 248,951 Amoxicillin capsule 74,130,200 2,973,745 Ciprofloxacin tablet 61,715,180 1,758,157 Paracetamol tablet 20,3243,144 2,267,328 Ceftriaxone vial 6,694,320 6,659,857 Gentamycin ampoule 6,709,100 803,846 Medroxyprogesterone vial 111,000 26,375 Omeprazole capsule 1,061,362,374 3,056,354 Levonorgestrel/Ethinyl Estradiol tablet 128,640 13,736

The above data shows (based on registered pro-forma) the total quantities and value of medicines requested for importation into the country by pharmaceutical import companies. However, data is not complete because during the stated period there was no any clear documentation system regarding the importation of medicines in the GDPA/Pharmaceutical Planning Department.


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ANNEX D. DISTRIBUTION OF PROVINCES FOR SAMPLE COLLECTION Distribution of Provinces by Zones Zone Main

Province Number of Provinces Total

West Zone Herat Badghis, Bayan, Farah, Ghor, Herat 5 North East Zone Badakhshan Badakhshan, Baghlan, Kunduz, Takhar 4 South East Zone 1 Ghazni Ghazni, Paktika 2 South West Zone Kandahar Daykundi, Helmand, Kandahar, Nimruz,

Uruzgan, Zabul 6

South East Zone 2 Khost Khost, Paktia, Logar 3 Central Zone Kabul Kabul, Kapisa, Panjshir, Parwan, Wardak 5 North West Zone Balkh Balkh, Faryab, Jawzjan, Samangan, Sar-e-Pol 5 East Zone Nangarhar Kunar, Laghman, Nangarhar, Nurestan 4 Total 34


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ANNEX E. ANALYTICAL LABORATORY TESTING CARRIED OUT ON MEDICINES

Medicine Dosage form

Identification Assay Uniformity (weight variation)

Disintegration Dissolution Sterility Bacterial endotoxins

pH Pharmacopoeia

Amoxicillin Oral solid

x x x x USP

Omeprazole Oral solid

x x x x USP

Alprazolam Oral solid

x x x USP

Atenolol Oral solid

x x x USP

Levonorgestrel/Ethinyl Estradiol

Oral solid

x x x USP

Paracetamol Oral solid

x x x x USP

Ciprofloxacin Oral solid

x x x x USP

Ceftriaxone Injection x x x x x USP Gentamicin Injection x x x x x USP Medroxyprogesterone Acetate Depot

Injection x x x x x USP

Oral Rehydration Salt Powder x x IP Medicine Form Pharmacopeial Standard Amoxicillin Oral

solid The method of testing was as per USP-32. Identification was carried out using TLC. Weight variation was done, and the minimum, maximum and average weights were provided. The % Risk Specific Dose (RSD) was given for each sample tested. Time for disintegration was measured in minutes. Assay values were presented in milligrams with a reference of 90 – 120 percent. Three values were provided, one of which was the average.

Omeprazole Oral solid

The method of testing was as per USP-32. Identification was carried out through the retention time of the sample. Assay values were presented in milligrams. Three (3) values were provided, one of which was the average. For the dosage uniformity, ten (10) measurements were taken in milligrams for each sample, plus an average. The dissolution test was done at acid resistance and buffer stages.

Alprazolam Oral solid

Identification, assay and dissolution were done by high performance liquid chromatography (HPLC), as per USP-32. Results were presented in milligram per tablet.

Atenolol Oral solid

Identification, assay and dissolution were done by HPLC, as per USP-32. Results were presented in milligram per tablet.


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Levonorgestrel/Ethinyl Estradiol

Oral solid

Dissolution (uncoated and coated tablets NLT 85 percent Q and 60 percent Q respectively), assay and uniformity of dosage were carried out separately for Levonorgestrel and Ethinyl Estradiol. Results were presented in milligrams per tablet.

Paracetamol Oral solid

Identification, weight variation, assay and disintegration were carried out and presented as per USP-32.

Ciprofloxacin Oral solid

Identification, weight variation, assay and disintegration were carried out and presented as per USP-32.

Ceftriaxone Injection Identification, assay (90 – 125 percent), pH (3.0 – 5.5), sterility (MF method), and bacterial endotoxins of NMT 0.20EU/mg were done in accordance with USP-32.

Gentamicin Injection Identification (TLC), assay (90 – 115 percent), pH (6.0 – 8.0), sterility, and bacterial endotoxins of NMT 0.71EU/mg were done in accordance with USP-32.

Medroxyprogesterone Acetate Depot

Injection Identification (Infrared), assay (90 – 115 percent), pH (3.0 – 7.0), sterility (MF method), and bacterial endotoxins of NMT 88.0EU/mg were done in accordance with USP-32.

Oral Rehydration Salt Powder This test was carried out in accordance with Ph. Int. The combined product and individual components (Sodium, potassium, chlorides, citrate and glucose) were duly identified. Assays of all the components were presented in percentages (90.0 – 110.0 percent).


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ANNEX F. LIST OF MANUFACTURING COMPANIES OF MEDICINES COLLECTED AND TESTED IN JANUARY 2010 Number of Products Sampled from each Manufacturer

Manufacturers of Medicines Sampled and Tested

One product • ABDI Ibrahim • ABKA • Amir Pharma • Asia-Pharma • Astra • Beximco

Pharmaceutical • Bhiwadi • Binging • Blenax • Bosch • Cadila Pharma • Caylex Pharma • Cedon • China • Cirin Pharma • Davis Pharma • Dana-Ph-Tabriz Diwioc

Pharma • EFROZ • Examon • Feladilfia • Gracure Pharma • Haoslam bior • Highnoon • Hilton • Honhay welcam • HOSUR • ICI • Indus Pharma

• Jaber ibn hayyan Pharma

• Jackson Labs • Jalphar • Jiamsu pengygo • KANT H-Ciar • Kausar • Khalid Arshad • Layuq Pharma • Maiden

Pharmaceuticals • Manor • Mecter • Medicament • Medicament Biotic • Melan Labs • Mission Pharma • Montriac • MSI • Mustafa nawzad • Neon • Netro Pharma • New-Ph • Nexuf • Ningbo • NovartiPan Pharma; • Paramal • Parke Davis • Pharma Wise • Phartac

• Pumacina • Rotexmedica • Samjin • Sanauita; • Sanavita Pharma • Sandoz • Sandoz Dassia

Novartis • Scilife • Searle • Shanghi • Shanghi Midicin • SmithKlein and French • Spridef • SquarePharmaceuticals • Stinly Subhan Darou • Sujonel • S-Z-P • Tabriz • TAS Pharma • TRAX TF • Trog • Unicare; • Unitic Pharmaceutical • Venture Pharma • Werrick • XIER Pharma • Zahrawi • Ziska

Two products • Afghan American • Arie Pharma • Benson • Bentic • Biophrama; • Daewon Pharma • Darou Pakhsh • Ginira Pharma • Hankok

• Incepla • IRZAK-B-I • Loqman • Medicament Beutic

Pharma • Micro Lab • Nonging

• Pharmawise • Porisina • Puurs • Saviour • Scotmann • Sobhan Darou • Spic • Wilson

Three products Combitic Global; Famycare; Marlex; MBL; Pharmacia; Red Lion Four products Aboraihan; Arbbro; Caspian Tamin; Emroz; Farabi; Indo pharma; Julphar; Nabi

Qasem ; Royal International


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Five products Holden; Olden; Pharbat; Razak; Samisaz; Sinochem; Tehran Chemie Six products Cipla; Zafa Seven products Organon Eight products GSK; Pfizer; Schering; Shijiazhuang Nine products Merck Ten products Gland Pharma Eleven products Davis Pharmaceutical Twelve products Medicamen biotech Fifteen products Wyeth Eighteen products Exir


47

ANNEX G. LICENSED DRUG LIST AND ESSENTIAL DRUG LIST OF MEDICINES THAT HAVE THIN-LAYER CHROMATOGRAPHY METHODS Table 10. Minilab ® Thin Layer Chromatography (TLC) Method Coverage of Licensed Drug List and Essential Drug List.*

No. TLC Method in GPHF Minilab ®

Anatomical Therapeutical

Chemical (ATC) Code

Licensed Drug List

Essential Medicines List

1 Glibenclamide A10BB01 X X 2 Furosemide C03CA01 X X 3 Griseofulvin D1BA01 X X 4 Prednisolone H02AB06 X X 5 Chloramphenicol J01BA01 X X 6 Ampicillin J01CA01 X X 7 Amoxicillin J01CA04 X 8 Phenoxymethylpenicillin J01CE01 X X 9 Cloxacillin J01CF02 X X 10 Cefalexin J01DA01 X 11 Cefuroxime J01DC02 X 12 Cefixime J01DD08 X 13 Trimethoprim J01EA01 X X 14 Sulfamethoxazole J01EC01 X X 15 Erythromycin J01FA01 X X 16 Ciprofloxacin J01MA02 X X 17 Rifampicin J04AB02 X X 18 Isoniazid J04AC01 X X 19 Pyrazinamide J04AK01 X X 20 Ethambutol J04AK02 X X 21 Indinavir J05AE02 X X 22 Zidovudine J05AF01 X X 23 Didanosine J05AF02 X X 24 Stavudine J05AF04 X X 25 Lamivudine J05AF05 X X 26 Nevirapine J05AG01 X X 27 Acetylsalicylic acid N02BA01 X X 28 Paracetamol N02BE01 X X 29 Metronidazole P01AB01 X X 30 Chloroquine P01BA01 X X 31 Quinine P01BD01 X X 32 Pyrimethamine P01BD51 X X 33 Artemether P01BE02 X X 34 Albendazole P02CA03 X X 35 Artesunate P03BE03 X X 36 Salbutamol R03AC02 X X 37 Aminophylline R03DA05 X X *[http://www.gphf.org, accessed 07 March, 2011]

http://www.gphf.org/


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Table 11. Additional Active Ingredients of Medicines in Licensed Drug List that are covered by Unofficial Thin Layer Chromatography Methods**

No. TLC Method in Minilab ®

ATC Code Licensed Drug List Essential Medicines List

1 Allopurinol M04AA01 X X 2 Betamethasone H02AB01 X 3 Carbamazepine N03AF01 X X 4 Cefradine J01DB09 X 5 Chlorpheniramine R06AB04 X X 6 Dexamethasone H02AB02 X 7 Diazepam N05BA01 X X 8 Digoxin C01AA05 X X 9 Diphenhydramine R06AA02 X X 10 Ergotamine N02CA02 X X 11 Gentamicin J01GB03 X X 12 Hydrochlorothiazide C03AA03 X X 13 Ibuprofen M01AE01 X X 14 Imipramine N06AA02 X 15 Indomethacin M01AB01 X 16 Ketoconazole J02AB02 X X 17 Medroxyprogesterone inj G03AC06 X X 18 Methyldopa C02AB01 X 19 Neomycin J01GB05 X 20 Nitrofurantoin J01XE01 X X 21 Norgestrel G03A X X 22 Nystatin A07AA02 X X 23 Penicillin procaine J01CE01 X X 24 Phenobarbital N03AA02 X X 25 Phenytoin N03AB02 X X 26 Promethazine R06AD02 X X 27 Streptomycin G01GA01 X X 28 Theophylline R03DA04 X 29 Triamcinolone H02AB08 X 30 Triamterene C03DB02 X 31 Vitamin A (retinol) A11CA01 X X 32 Warfarin B01AA03 X **Kenyon AS, Layloff T. A Compendium for Rapid Screening of Pharmaceuticals by Thin-Layer Chromatography. St Louis, MO: Food and Drug Adinistration. [http://www.pharmweb.net/pwmirror/library/pharmwebvlib.html, accessed 07 March 2011]

http://www.pharmweb.net/pwmirror/library/pharmwebvlib.html

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