Final Report Summary - AMASA (Accessing Medicines in Africa and South Asia)
Executive Summary:
Executive summary
The AMASA consortium is a collaboration of partners in Europe, South Asia and Africa investigating the complexity of pharmaceutical supply chains in low- and middle-income counties and their impact on access to essential medicines. This 3-year project received a €3 million grant through the European Commission’s Seventh Framework Programme (FP7). The eight institutions which are involved in the project are: University of Edinburgh (UK), as coordinating institution, University of Ghent (Belgium), Swiss Tropical and Public Health Institute (Switzerland), Mbarara University of Science and Technology (Uganda), Makerere University (Uganda), University of Western Cape (South Africa), Foundation for Research in Community Health (India), and Queen Mary and Westfield College, University of London (UK).
Access to medicines is a key concern of governments, NGOs and citizens around the world. Much of the research carried out in this area, however, investigates barriers to access through the prism of patient or health system variables; i.e. cost, price, availability, tolerance, compliance, distance and user charges. The alternative discourse is grounded in considerations of intellectual property and barriers to pharmaceutical production, distribution and research innovation. These two elements dominate the policy discourses worldwide, but their interplay and the effects of other regulations at national and international levels are under-examined and not well described.
The AMASA project was stimulated by earlier research conducted at the University of Edinburgh under the leadership of Professor Roger Jeffery. This project, entitled Tracing Pharmaceuticals in South Asia (http://www.csas.ed.ac.uk/research_projects/tracing_phramaceuticals) was funded by ESRC-DFID and focused on three pharmaceutical products in India and Nepal and took a whole-system perspective grounded in public health and population approaches to health care and drug delivery. This required an understanding of the clinical evidence base for each drug, and how this evidence plays out in practice when national and international regulations governing production, cost and access are considered. One of the main findings of this research was the need for further investigation of the complex interplay between the regulations that govern pharmaceutical production and delivery in the formal and informal networks of health care in the study countries.
The main aim of the AMASA research project was to investigate how the interplay of patent regimes, pharmaceutical regulation, availability of drug production facilities, health care infrastructure and service provision, and engagement by foreign donors influence appropriate, affordable access to medicines in South Asia and Sub-Saharan Africa. We have mapped patterns of production, distribution, supply and consumption of study medicines within seven health care areas – HIV/AIDS, Malaria, Reproductive Health, Tuberculosis (TB) Control, Mental Health, Pain Management and Diabetes – with specific consideration for the situation our study countries. We have also investigated the strategies and influence of selected Indian producers who are active as exporters, partners in joint ventures, or as direct producers in the selected South Asian and African countries.
The project goes beyond most studies on pharmaceutical policy that focus on only a small aspect of the supply chain whether it is research and development, pricing or patient adherence. In this project, we took a multi-disciplinary approach to incorporate the entire pharmaceutical supply chain from production down to consumption. In order to achieve this ambitious goal, seven study medicines were followed through the supply chain in three different settings: Uganda, South Africa and India.
In addition, as Indian companies invest more and more in production facilities throughout Africa, understanding more about these North-South and South-South partnerships and their associated knowledge and technology transfer policies becomes relevant. India’s approach to patent recognition is seen as a model that should be implemented in other developing countries. The unique perspective of the AMASA project is its ability to shed light on various aspects of these relationships through the lens of our study countries.
The results of the project are being used to provide recommendations on suggested improvements for various points of the supply chain, through a plan of engagement with relevant stakeholders, such as regulatory agencies and training institutions in each of the focus countries. Specifically, we seek to develop and implement a capacity building initiative in drug regulation aimed primarily at personnel associated with their national drug authorities. Analysing the impact of TRIPS, GMP and other aspects of international trade regimes on access to medicines in these countries has allowed us to propose measures to improve the regulatory and training arrangements to enhance access to medicines in the full range of meanings described in the original proposal. We have generated both nationally and internationally targeted reports, workshops, stakeholder meetings, publications, and policy briefs to ensure that the outcomes of the AMASA project will have maximum impact.
Project Context and Objectives:
Access to medicines remains a critical issue for Asia and Africa, with approximately 40% of the African population and 50% of the South East Asian population living without public access to essential medicines according to The World Medicines Situation 2011 published by the WHO. When the World Trade Organization was established and new rules were agreed for the trade-related aspects of intellectual property rights (TRIPS) there was concern that prices and availability of essential medicines for the poor would be compromised. It was feared that the extension of patent rights to countries such as India, where producers of generic medicines had developed low-cost alternatives to some patented medicines, would limit their exports. In the short-term (because of the varying time of compliancy for different countries ranging from 2005 in India to 2016 or longer in many Sub-Saharan African countries), protections were built in. Several agencies (including UNAIDS, the Global Fund, PEPFAR, and the Clinton Foundation) also mobilised to provide alternative sources of funding in low-income countries. These changes and their implications for access to other medicines for the poor, in fields where generic and patented versions of the same or competitive medicines are available, are under-researched and poorly understood.
The World Health Organization’s Inter-Governmental Working Group (IGWG) report was adopted by the Global Health Assembly in May 2008. Element 6 of this report emphasises that “mechanisms to regulate the safety, quality, and efficacy of medicines and other health products coupled with adherence to good manufacturing practices and effective supply chain management, are critical components of a well-functioning health system”, and that international agreements that might impact on these aspects and therefore access to medicines need to be monitored. The WHO supports a number of countries in their drug regulation efforts. More broadly, its pharmacovigilance efforts are carried out by the Uppsala Monitoring Centre located in Uppsala, Sweden, through international drug monitoring services and the tracking of adverse reactions to pharmaceuticals.
Our research relates to several EU agendas which are oriented towards the pursuit of the Millennium Development Goals (MDGs), particularly those concerning maternal mortality, HIV/AIDS, TB, and malaria. These include the EU’s goal of strengthening EU-Africa dialogue through the Sub-Saharan Africa component of the project, as well as promoting knowledge and technology transfer, and increasing the involvement of African scientists in international collaborative science and research and development projects with respect to health, in contribution to the broader economic and social development envisaged in the MDGs. The evidence gathered through this research will contribute to the knowledge base informing the EU’s actions with respect to improving funding systems to fight HIV/AIDS, TB and malaria, and in particular help to assess its goals of appropriate pharmaceutical-related transfer of technology, capacity building, and local production of drugs in developing and least-developed countries. In compliance with Paragraph 7 of the European Parliament 2007 resolution on TRIPS and access to medicines, this research acknowledges the role of broader factors in addition to patent law that impact on access to medicines, such as health system infrastructure, local manufacturing capacities, and the pricing of pharmaceuticals, and will contribute to knowledge regarding the combined impact of these various factors.
This work also promotes the EU’s agenda of Policy Coherence for Development (PCD), in complying with the EU’s research policy of investigating areas of interest for developing countries, particularly through international cooperation. The work of this research effort is compatible with the European and Developing Countries Clinical Trials Partnership (EDCTP), specifically on AIDS TB and malaria, insofar as it promotes networking between partners in the north and the south, and capacity development and building through research partnerships. The UK Department for International Development (DFID), in collaboration with the World Bank and the WHO, launched the Medicines Transparency Alliance (MeTA), whose goal is to “improve access and affordability of medicines for the one third of the world’s population unable to access basic and essential medicines due to high cost or local unavailability”. Our research complements their activities by helping to provide relevant evidence in advance of such an initiative being introduced in the partner countries and by helping to locate these efforts within a wider framework of changes in international relationships.
Project Objectives
An inception workshop was held at the beginning of the project to fine-tune the general research framework around the project objectives and to confirm or modify the preliminary selection of diagnostic areas and specific medicines. The workshop refined the research questions around pharmaceuticals and specifically for the selected medicines, which included seven themes: production and acquisition, regulatory systems and policies, patents and trade issues, health systems funding and donor roles, supply chains and distribution, consumer and community interests, and study medicine evidence base critique. For each of these thematic areas the following research questions and objectives were developed.
Production/Acquisition
The research questions developed for production and/or acquisition of pharmaceuticals were:
• What are the production capacities of selected Asian and African countries with respect to the seven health areas of interest (HIV/AIDS, malaria, reproductive health, TB control, mental health, pain management and diabetes), and the one specified study medicine within each area?
• What is the balance, in each country and pharmaceuticals group, between imports, local production, and exports to other countries?
In each case we considered the different patterns of active pharmaceutical ingredients (APIs) and formulations and the distribution channels for these drugs at the national and regional level. From these research questions on production and acquisition two research objectives were identified: (1) to determine the production capacities in India, South Africa, and Uganda for selected study medicines and (2) to account for production, import, and export of selected study medicines in these specific contexts and internationally.
Medicines Regulatory Systems and Policies
The research questions developed for medicines regulatory systems and policies were:
• What are the national regulatory standards for production, quality control, distribution, and prescribing and dispensing of medicines?
• How are these regulations developed, what are the enforcement mechanisms, how do they work in practice, and what are the capacity issues involved?
• Over the past 10 years, what has been the importance of critical events (such as investigations into counterfeit drugs, periods of drug shortages, and/or significant increases in prices) in the development of regulatory control of pharmaceutical production and supply in each study country?
From these research questions on medicines regulatory systems and policies five research objectives were identified: (1) to examine the existing international and national policies and regulations (for production, quality control, distribution, and prescribing of medicines); (2) to describe the existing pharmacovigilance systems in each focus country; (3) to determine how well national policies and practices for production, quality control, and pharmacovigilence conform to best regulatory practices and standards (e.g. Good Manufacturing Practice (GMP); (4) to determine how counterfeit and substandard medicines are identified and dealt with; and (5) to determine how critical events have affected policies and regulations.
Medicines Patents and Trade Regulations
The research questions developed for medicines patents and trade regulations were:
• How are patterns of national and regional pharmaceutical production and supply affected by the TRIPS agreement, the Doha Declaration, and international standards for pharmaceutical production?
• What is the impact of other international regulations (such as the procurement decisions made by international agencies like the Global Fund) and bilateral trade agreements on access to medicines?
From these research questions on medicines patents and trade regulations four research objectives were identified: (1) to determine the existing trade regulations and policy which may impact medicines procurement (including bilateral or individual contracts and protection of commercial interests); (2) to determine the interaction of these regulations with access to medicines; (3) to describe the patent status of a medicine (such as when various formulations of the drug exist that are or are not under patent or in the application of a patent extension to use the drug for a new condition potentially altering access to the medicine to treat the condition coming off patent); and (4) to determine the implications and significance of process and product patents.
Health Systems Funding and Donor Roles in Access to Medicines
The research questions developed for health systems funding and donor roles in access to medicines were:
• At the national and regional levels, how are the relevant delivery systems (in HIV/AIDS, malaria, reproductive health, TB control, mental health, pain management and diabetes) organised, funded, financed, and implemented?
• What are the sources of funding for the health problems treated by the selected study medicines?
• How do these programmes interact with foreign donors and supply of pharmaceutical products and what are the implications for access to medicines?
From these research questions on health systems funding and donor roles in access to medicine three research objectives were identified: (1) to determine relative allocation of funding from international donors and national (public and private) funding for health problems associated with selected study medicines (focusing on specific study medicines where possible); (2) to determine how international and national procurement policies affect national health policy, acquisition, and distribution of selected study medicines; and (3) to determine the extent to which the delivery system of the selected drugs is carried out through the general public health system or through a parallel system (e.g. mission, for-profit and not-for-profit, donor-established, NGOs).
Medicines Supply Chains and Distribution
The research question developed for medicines supply chains and distribution was:
• What is the structure of existing supply chains? How many ‘chains’ are there and how do they overlap?
• What processes are in place for quality control at various levels of supply chains?
• What are the strongest and weakest links in supply chains and what makes them so?
• What commercial interests and incentives affect various steps in supply chains? (e.g. revising the nature of supply chains to eliminate middle men)
From this research question on medicines supply chains and distribution four research objectives were identified: (1) to determine the structure of the existing supply chains and potential complementarities and overlap between them; (2) to investigate the processes and capacity (infrastructure and personnel) of the systems for quality control at each level in the supply chain (eg. removal of expired medicines); (3) to identify and evaluate problem points in the supply chain influencing appropriate availability, quality, and cost; and (4) to identify commercial factors influencing structure and operations of supply chains.
Consumer and Community Interests
The research questions developed for consumer and community interests were:
• What are the effects of higher level policy and supply chains on access and use of medicines by patients?
• How does availability and price of medicines affect access?
• How do poverty, livelihood, gender, resilience strategies, and cultural concepts of illness affect consumption-related behaviour, and in turn, how does medicine consumption affect poverty alleviation?
Special attention was paid to adverse event reporting, drug formularies, inspection, monitoring, and pharmaceutical production. From these research questions on consumer and community interests four research objectives were identified: (1) to determine the availability and price to consumers of selected medicines; (2) to examine relationships of perceived affordability, poverty, livelihood, gender, resilience strategies, and cultural concepts of illness affecting consumption-related behaviour; (3) to determine how medicine consumption affects poverty alleviation; and (4) to compare the consumer views of the seven study medicines in the three study countries.
Medicines Evidence Base
The research question developed for the medicines evidence base was:
• What is the evidence base for use of each of the selected study medicines?
From these research questions on medicines evidence base two research objectives were identified: (1) to critically examine the literature to determine the validity of the research supporting use of the selected medicine for its specified use; and (2) to determine whether if and how off-label use is addressed in the literature for each of the study medicines.
International Perspectives
Additionally, within each of these project objectives, which tend to be more country- and medicine-specific, this research draws upon and extends four international perspectives: (1) the importance of strengthening public health management and health system delivery, pharmacovigilance and surveillance; (2) the Global Commodity Chains approach for pharmaceutical products in low- and middle-income countries; (3) health policy transfer and implementation and its suitability for various settings and situations; and (4) human rights from a global perspective and within the field of health care and the ‘right to health’. The international context of these perspectives was the subject of various cross-country inquiries and subsequent reports.
Project Results:
It was determined early on in the AMASA project that substantial background research was needed in each of the thematic areas described above with specific reference to the three focus countries. Therefore, substantial background research was undertaken and subsequently summary reports were written to determine what information had already been reported through scientific publications, government agencies, or international/national organisations. To accomplish this working groups were organised around these themes (see page 16 of DoW).
Each group performed background research in the specific topic area and provided a summary of the theme both within the national context of the focus countries as well as from an international perspective. A thorough analysis of these reports identified informational gaps in the currently available data. These gaps informed our research methodology and allowed the project to contribute novel data to these specific areas of research within the broader framework of access to medicines to achieve the greatest impact.
General Research Methodology
Work began with the development of a framework under which the project research would be undertaken. This project protocol included individual country plans and was crucial in developing the research methodology in which each site would design, collect, analyse, and present data within the project. The final selection of study medicines for each country was based on a number of specific criteria such as ensuring selected medicines are used routinely in study countries and cover a wide range of access and availability issues, limiting the chosen medicines to a manageable number to ensure the best possible research outcomes, allowing for cross-country comparisons, and showcasing different patterns of medicine distribution and use within and across countries. The selected study medicines were as follows:
• lamivudine, used for treating HIV;
• artemisinin-based combination therapies, used for treating malaria;
• oxytocin, used in reproductive health;
• rifampicin, used for treating tuberculosis;
• fluoxetine, used for treating depression;
• fentanyl, used for pain management; and
• metformin, used for treating type 2 diabetes.
Once these study medicines had been selected and the background literature reviews analysed sources of information were identified. Data was collected through semi-structured interviews, surveys, observations, and case studies.
Interviews were conducted with key informants within the specific thematic areas. Interviewees came from a variety of disciplines such as government, international organisations, academia, NGOs. The interview topics were organised in 11 categories: (1) producers (representatives from local pharmaceutical companies, if possible, or multinational companies with local impact); (2) regulators (individuals involved in regulation at the local or national level as well as those with an international perspective); (3) ministry of health (government officials with general knowledge related to the project theme areas or with specific knowledge of the target disease areas or study medicines such as national disease control programme officials); (4) health facility managers (facility managers at various levels of the health care system); (5) prescribers and pharmacists (clinicians of various types, i.e. generalists and specialists, in both the public and private sectors); (6) civil society activists (disease-related advocacy groups, community interest groups, professional and trade associations); (7) patent and trade officials (responsible government officials from national patent and trade offices); (8) distributors (government medical store managers or private distributors at various levels of the supply chain); (9) donor agency representatives (global and country-based key donor organisation officials); (10) community health workers (public sector health workers within health centres or clinics at the local level); and (11) consumers (individuals using the study medicines through public and private clinics). Interview schedules were developed for each topic with general questions, in order to allow for a cross-country analysis and an international perspective, and country-specific questions in order to provide the required information for national dissemination activities and, therefore, the most impact locally.
Surveys were conducted at private pharmacies and with consumers within the specific context of the selected study medicine. Pharmacy surveys (which also included sampling of ‘drug shops’, as they are referred to in Uganda) included obtaining a list of the specific study medicines available in that particular pharmacy/drug shop on that day which included dosages, formulations and prices, if available. In addition, responsible pharmacists or owners were asked a variety of questions about popular brands, requirement of prescriptions, consumer knowledge and preferences, inspections, supply management, and the issue of counterfeits or substandard medicines. Consumers of the study medicines were asked questions about their disease conditions, what medicines they were taking, where the obtained them, preferences for specific medicines, interactions with health care providers, and if they had any issues obtaining or taking the prescribed medicines.
Facility observations investigated public sector health facilities for medicine availability and storage conditions. The case studies conducted in all countries were primarily concerned with stockouts of the study medicines that occurred during the project or local pharmaceutical production.
It was also necessary to identify the specific locations in each country where the research would be undertaken. Uganda selected four districts (Kampala, Mbarara, Apac, and Bundibugyo) that represented both urban and rural regions of the country and, therefore, different levels of availability of health care services. India also selected four districts (Mumbai, Dhule, Nagpur, and Sangli) but all within one state, Maharashtra, in order to investigate district-level issues related to study medicines all within one administrative area. South Africa chose to compare two provinces (Western Cape and Eastern Cape) based on contrasting health care system functionality within the country.
Pharmaceutical Production, Distribution, Prescription, Consumption, and Regulation in Uganda, India, and South Africa
The background research which was completed by the working groups described above were condensed into country-specific reports on the production, distribution, prescription, consumption, and regulation of pharmaceuticals in each of the focus countries: Uganda, India, and South Africa. These reports provided the necessary background information to support the project methodology in achieving three main country-specific objectives of the AMASA project: (1) to evaluate how the interplay of patent regimens, pharmaceutical regulation, availability of drug production facilities, health care infrastructure and engagement of foreign donors influences affordable access to medicines; (2) to identify multiple approaches for accessing needed affordable and good quality medicines; and (3) to identify approaches for limiting inappropriate and irrational use of the study medicines. Key findings from the AMASA project specific to the individual focus countries are described below.
Uganda
Production
According to the Ugandan Ministry of Health, it is estimated that approximately 85-90% of Uganda’s pharmaceutical products are imported from countries such as India and China. The remainder is produced by a handful of local manufacturing facilities. The market is essentially generic with price being the major determining factor for purchase and use. Medicine supply is acquired through both public and private procurement as well as by NGOs, faith-based organisations and donor agencies which requires an extensive coordination strategy to ensure that all required medicines are made available while minimizing stock outs and expiries. For obtaining essential medicines donor funding has been used to provide treatments for malaria, tuberculosis, and HIV/AIDS through the public sector and vertical programmes which can lead to some over-funded programmes and stockouts in others. As this is not a sustainable means of obtaining sufficient essential medicines some countries, such as Uganda, have begun to invest in local production of pharmaceuticals to increase national self-sufficiency.
At present, five to six large- and six small-scale pharmaceutical manufacturers operate in Uganda whereby only secondary (finished products) and tertiary (packaging and labelling) levels of production occurs. Many of the manufacturing plants that do exist in Uganda, such as Quality Chemicals Industries Limited (QCIL), are joint ventures with foreign companies and rely heavily on foreign investment. It is claimed by the local Ugandan Pharmaceutical Manufacturers Association that these companies, if functioning at full capacity, can meet the demand for many of the essential medicines for Uganda’s population. However, this is not happening in practice because local companies cannot employ economies of scale due to the relatively small local market, high energy cost with frequent power interruptions, competition from more efficient foreign suppliers (particularly India and China) and a lack of access to donor funding largely due to stringent compliance conditions regarding quality assurance attached to these funds. For example, a local production plants, Kampala Pharmaceuticals, was affected by national treatment policy change that cost them a great deal of money and other substantial losses. In addition, many donor agencies require medicine suppliers to be WHO prequalified to be eligible for procurement tendering. This is a significant hurdle for local manufactures but one that some developing countries, such as Uganda, are attempting to overcome. Therefore, the gap between demand and local production capacity still results in a heavy dependency on imports.
In depth interviews were conducted in Uganda with local manufacturers, policy makers, medicine distributors, and officials from the National Drug Authority in order to gain insight into the status of local production of pharmaceuticals. The local manufacture of essential medicines in Uganda is considered a key intervention for sustainable access to medicines. Local manufacture of antimalarial and antiretroviral drugs has gained momentum over the past 10 years. The private sector is playing the leading role, a process catalysed by government incentives and partnerships. Incentives documented include market guarantees from the government that have helped to establish and boost Quality Chemicals. Other incentives include: free land, and facilitation of importation of active ingredients (mainly from China and India). There is a massive transfer of technology into Uganda together with considerable technical assistance and expertise from India. The Quality Chemicals factory passed Good Manufacturing Practice (GMP) inspection by WHO. The existing production line however is not optimally utilized due to small orders, and this is being boosted through exploring new distribution ventures in regional markets such as Rwanda, Congo and southern Sudan. Furthermore, active pharmaceutical ingredients and many excipients are imported, primarily from India and China. The cost of the active pharmaceutical ingredients alone can be over 80% of the production cost. Currently, Quality Chemicals has plans to manufacture active pharmaceutical ingredients for artemisinin-based medicines.
In particular, the AMASA project examined in great detail the Government of Uganda’s position in encouraging local pharmaceutical production through the implementation of its health and industrial policies. This was done through a case study of Quality Chemicals and the processes that led to the establishment of this joint venture between the Government of Uganda and Cipla Limited in India. Specifically, an evaluation of the incentives given by the Government of Uganda for such an enterprise and whether local pharmaceutical production within this context is beneficial for Uganda, if the activities of Quality Chemicals can be replicated in Uganda, and finally, whether Quality Chemicals is a model for Africa was completed. Data was primarily obtained by conducting semi-structured interviews conducted with key informants and was supplemented by a review of the literature, newspaper reports, and relevant government policies. Collected information was evaluated using the WHO local production for public health framework. Although local pharmaceutical production is mentioned in current health and industrial policies in Uganda the implementation plans for these policies do not provide any detail on how local pharmaceutical production could or should contribute to the development of both the health and industrial sectors. Without harmonisation of these policies and the inclusion of incentives to reduce price and availability of locally produced essential medicines it does not appear that such endeavours will improve access to medicine in Uganda.
Distribution
In Uganda, there are various distributors of medicines in operation. The major ones include the National Medical Stores and the Joint Medical Stores that control most of the medicine distribution in the country. There are also various importers and wholesalers, some manufacturers, as well as medicine delivery stores in the districts. Key informant interviews were conducted with representatives from the two large distribution stores as well as a selection of importers and wholesalers. The interviews focused on issues such as: guidelines for selection forecasting, procurement, ordering, stock outs, warehousing and storage, transportation and distribution, the political and administrative regulatory framework, and views on the main challenges. Most distributors organised their businesses with a clear divide between sections dealing with administration, finance, technicalities, marketing, and procurement and distribution. They reported human resource challenges such as inadequate training of staff and limited availability of technically trained people. This was attributed in part to a severe shortage of skilled professionals and high staff turnover. Big businesses were found to employ people with some general sales training but with little specific knowledge about medicines sales. Logistics management was mostly done using automated systems and these systems help in quantification and forecasting for minimum quantities. Uganda’s National Drug Authority regulates distributors and quantities to be imported, based on their registration as either wholesaler or retailer. There was a noted focus of the Uganda’s National Drug Stores to push ergometrine and misoprostol as opposed to the earlier choice of oxytocin for third level health clinics. There was stockpiling of misoprostol whilst at the same time reported oxytocin stock outs for some months.
Prescription and Consumption
The prescription and consumption of six study medicines in Uganda covering malaria (artemether-lumefantrine), tuberculosis (rifampicin), HIV/AIDS (lamividine), depression (fluoxetine), diabetes (metformin) and labour (oxytocin). Prescription of these medicines was dependent on the level of the prescriber within the health system. Lower-level prescribers (nurses/midwives) can prescribe artemether-lumefantrine (typically found under the brand name Coartem) to treat uncomplicated P. falcipirum malaria and oxytocin for the prevention of post-partum haemorrhage. Higher-level prescribers can prescribe five of the study medicines with the exception of fluoxetine, used in the treatment of depression and anxiety disorders, which requires a prescription from a specialist. All prescriptions can be cashed either from private or public sectors. Prescriptions made in public facilities can be cashed privately in private clinics due to stock outs. Private clinics have their own private pharmacies within their clinics. This is the same for public facilities. Most prescribers could not differentiate between originator and generic medicines. Medical representatives greatly influenced some prescribers through incentives given during drug promotions.
Artemether-lumefantrine and was the most prescribed due to the high incidence of malaria in Uganda. Many artemether-lumefantrine brands are circulating in the market but this did not alter the cost of these medicines in some districts, as they remained high and unaffordable. This led to misuse by patients who couldn’t afford a full dose with some families sharing a single dose of artemether-lumefantrine to treat all sick family members. Quinine was the primarily alternative to artemether-lumefantrine for most prescribers. Rifampicin and lamivudine were dispensed by a majority of prescribers especially in Level 3 health centres but were not well described except in combination therapies. Most prescribers complained about the interaction of rifampicin and nevirapine, widely available as a combination antiretrovirals, which can compromise adherence to treatments. For these medicines in particular, supply was not dependable to some health centres and some reported regular stock outs for considerable amounts of time with no substantial or planned remedy or fall back options to purchase emergency stocks. Fluoxetine was not on the essential drug list and so all health centres getting their medicines from the National Medical Stores were supplied with an alternative, amitriptyline. Therefore, the majority of prescribers were unaware about fluoxetine and instead used amitriptyline for treatment of depression. Misoprostol was widely used for post-partum haemorrhage management despite oxytocin being recommended as the first line drug. Preferential use of misoprostol was attributed to ease of use (is administered as a tablet as compared to oxytocin which requires an injection), ease of storage (can be stored at room temperature where oxytocin is temperature-sensitive), and wide availability. Misoprostol was also used for other off-label uses such as induction of labour, abortions, and post-abortion care.
In order to evaluate consumption of the study medicines, consumers of these medicines were surveyed. Many consumers complained of unavailability of drugs at some health facilities, inadequate information on medicines, and experiences of side effects with the study medicines. Lack of money for transport and food during treatment were also reported as major challenges related to treatment with the study medicines. A number of people reported obtaining medicines from pharmacies and drug shops using hospital prescriptions. For most medicines, consumer acceptability depended on perceived efficacy, side effects, and the number of pills required. Consumer demand and/or desire to impress consumers were found to be key influences for prescriptions and dispensing especially among private prescribers.
Regulation
In Uganda, the regulation of medicines is overseen by the National Drug Authority. However, professional councils (i.e. medical, pharmacy, nurses and midwives, and allied health professional councils) play an important role in regulation of medicines through the regulation of professionals involved in handling of medicines at various levels of the health care system. Officials from the National Drug Authority were selected for interviews because of the responsibilities they perform in relation to drug regulation in the country. In addition, representatives from various professional councils were interviewed as well. Interviews on the regulation of pharmaceuticals addressed issues such as: capacity limitations of regulatory agencies (including staff, infrastructure, financial); the main challenges to regulatory activities; enforcement of noncompliance to Good Manufacturing Practice and Good Distribution Practice and other features of regulatory noncompliance; regulation of medicine promotion; differences in regulatory practices between public and private sector operations; changes in regulations and their impact over the past decade or two; drug product reviews; pharmacovigilance activities; and policy operations for counterfeit, fake and substandard medicines.
One of the primary concerns raised during these interviews was an acute shortage of human resource capacity faced by the regulatory sector. This was attributed to a lack of adequate training and a shortage of qualified professionals but also partly due to inadequate funding. There are limited funding opportunities for medicine regulation with the World Health Organization taking the lead through the training of inspectors using the International Accreditation System for Good Manufacturing Practice. It was found that companies pay a lot of money for inspections to be carried out. Fortunately, there is sharing of regulatory information with Kenya, Tanzania, including Good Manufacturing Practice, which can help prevent redundant inspections from being done. It was also established that in addition to the formal Good Manufacturing Practice inspections the Ministry of Health has a parallel system that does joint inspections with the Allied Health Professionals Council, the Medical and Dental Professionals Council, and the Nurses and Midwives Council. In regards to tracking the quality and safety of medicines in the country, the government has established four pharmacovigilance centres in various regions of the country with each centre being responsible for adverse drug reaction monitoring and documentation. However, drug quality surveillance is mostly done during preregistration and no sampling is currently done during inspections. This leaves room for the introduction of counterfeits and substandard medicines to enter the market. Inspectors from the National Drug Authority don’t impound substandard medicines, nor is any form of legal action taken against those responsible. Cases of fake medicines, counterfeits, or operating without licenses, take a long time to be dealt with, with very small fines imposed on those found guilty. Counterfeits and substandard medicines left to enter the market without consequence can have a devastating effect on public health outcomes in the country.
India
Production
The Indian pharmaceutical industry is one of the largest among developing countries with a global market share of over 3% and worth an estimated US$12.6 billion in 2009. The leading 250 companies control 70% of the market with market leaders holding nearly 7% of the market share. India is the world leader in generics production accounting for approximately 22% of the global total. A recent report by KPMG indicates that the Indian pharmaceutical industry consists of 250-300 large to moderate firms with nearly 20,000 small firms. McKinsey & Company reported that with an estimated compounded annual growth rate of 13-14% it will be worth US$55 billion by 2020. Formulations account for most of the pharmaceutical market with bulk drugs, such as active pharmaceutical ingredients, accounting for the rest (less than 20%). Requirements for the majority of bulk drugs and almost all finished products are met within India itself.
The CIMS database indicates that both single drug formulations and fixed dose combinations that include our study medicines are available in the Indian market. For example, rifampicin alone is produced by nearly 30 companies with over 120 different brands. Unfortunately, precise data on drug manufacturing capacity, volumes, actual prices, and sales are not available in the public domain.
Distribution
The medicine distribution system in India includes manufacturers, clearing and forwarding agents, stockists, wholesalers, and retailers. The clearing and forwarding agents are responsible for the storage of medicines coming from the manufactures as well as maintaining a stock of medicines until requested by the stockists eventually ending up in retail shops or hospitals. Overall, the distribution system in India is generally regarded as highly fragmented and supply chain management remains an ongoing problem. A description of the supply chain for each of the study medicines is listed below.
• The distribution of antiretrovirals for treating HIV/AIDS is done through established ART centres. However, limited inspection of stocks can lead to variations in quality due to the presence of spurious drugs or substandard medicines due to medicine expiry or inappropriate storage conditions. In addition, the lack of a centralised supplier database can result in fluctuations in price and quality.
• No specific data was found on the distribution system for artemisinin-based therapies in India although, in theory, it would fall under the procurement and distribution system of the National Vector Bourne Disease Control Programme implemented by the Ministry of Health.
• No specific data was found on the distribution system for oxytocin in India although it is widely available in India; used in both urban and rural settings and can be readily purchased over the counter in local pharmacies. The distribution of heat-sensitive oxytocin to rural regions of India with a potential lack of proper storage conditions and ease of purchase from local pharmacies is cause for concern and should be evaluated by the Ministry of Health and Family Welfare.
• The National TB Control Programme administers treatment programmes for tuberculosis through a central procurement system and over 4 million DOTS centres across the 35 states of India. Primarily, medicines are transported from the manufacturer to Government Medical Stores Depots and then distributed to the local treatment centres via State Drug Stores and district-level depots. The strength of the supply chain management system for rifampicin have been achieved through improvements in the management system which allows for more accurate predictions of use and therefore procurement projections and a centralised system which can transfer buffer stocks easily to depots with medicine shortages. In addition, the increased shelf life of rifampicin has improved medicine quality/stability and reduced medicine expiry and related stockouts. Weaknesses in the rifampicin distribution system come from the lengthly procurement process, lack of an instantaneous response to drug shortages to peripheral facilities, and the issue of the distribution of government procured medicines through private pharmacies.
• No specific data was found on the distribution system for fluoxetine although some information was retrieved regarding the availability of fluoxetine in India. The majority of prescriptions for fluoxetine come from the private sector predominantly in urban settings.
• Metformin should be distributed through the National Programme for Prevention and Control of Diabetes, Cardiovascular Diseases and Stroke however no progress has been made with expanding this programme since a 10-state pilot study was completed in 2008. The majority of prescriptions for metformin come from the private sector.
In relation to the tuberculosis and malaria programmes, the expectations of public health facility staff and the programme staff over the coordination and supply medicines are problematic. This is due to lack of clarity over roles and responsibilities between pharmacists at public health facilities and vertical programme staff. The vertical programmes do not have pharmacists operating effectively at the local facility levels and this limits access when expectations are placed on local public health staff. For the study medicines, four are contained within well-established public health programmes (malaria, tuberculosis, HIV, and maternal health) and provided evidence of adequate systems of distribution and supply as well as rational drug use compared with the less well-established programmes for diabetes and mental health. The national programmes for diabetes and mental health are underdeveloped and access through the public sector is poor. Access to these medicines is mainly through the private sector, which is not free of charge. In addition, the irrational production and distribution and consumption of study medicines was evident, especially for metformin, in the four districts we studied.
Prescription and Consumption
There are no data collected by the government on public and private prescriptions. As a result there are no data on prescribing volumes for any of these study medicines. The absence of routinely collected patient and prescribing data render it impossible to analyse met and unmet need for any of the study medicines associated with national disease control programmes underpinning medicine prescription and use. Given the lack of prescription and consumption data ensuring efficacy and safety of all medicines becomes of the utmost importance. As there was found to be limited evidence of efficacy and safety for some of these study medicines, especially fixed dose combinations for metformin (see subsequent section on regulation), there is a need to review efficacy criteria as part of market approvals.
Regulation
The drug regulatory system of India must cover a vast country of 3,287,240 square kilometres and an immense population of 1.029 billion. The 2011 Indian census found that 70% of the population live in rural areas, further increasing this supervisory challenge. India now ranks 3rd in terms of volume of pharmaceuticals production (10% of global share) and 14th largest by value allowing India to meet 95% of its domestic demands for pharmaceuticals. According to a Ministry of Health and Family Welfare Expert Committee Report from 2003 (knows as the Mashelkar Report), there were 418,411 sales licenses including 253,666 retail licenses and 145,447 wholesale licenses in India. The report also stated that there were 935 drug inspectors to inspect these units. Problems with this system exist. For example, manufacturers submission of periodic safety update reports is incomplete and the reports are not being evaluated by the Central Drugs Standard Control Organisation, India’s national drug regulatory body. Recommendations made by the Mashelkar Report to substantially improve medicine regulation still need to be implemented 10 years later. Furthermore, parliamentary and academic reports have highlighted the widespread production and use in India of ‘irrational’ medicines and questioned the rigour of the underpinning regulatory processes and capacity of the Central Drugs Standard Control Organisation.
Consistent with the Mashelkar Report, the AMASA project uncovered evidence of inadequate resources, poor infrastructure, and insufficient workforce capacity for drug inspectors and quality control labs at State level. This has serious implications for access, safety and quality. There is a lack of freely accessible and publicly available systematic data on manufacturing, sales, and prescribing volumes of marketed products in India. The current data on total number of sales units and regulatory staff in the country is not centrally available on drug regulatory agency websites or in any other literature and no data for production and import or sales volume and value by product and manufacturer for any of study medicines were available. Furthermore, the lack of regulation around Good Distribution Practices previously mentioned limits enforcement of the Drug and Cosmetic Rules regarding transport and storage, which adversely impacts the availability of high quality and safe essential medicines to the population. Overseeing public health in India is the responsibility of state authorities. However, the pharmaceutical industry does not observe state borders nor state public health needs. It establishes and disestablishes in response to state subsidies, land donations, tax breaks, and commercial interests. This conflict between trade and public health makes it difficult for states to respond to the regulatory and public health needs and requirements in a timely fashion. It also impacts on the capacity of quality control labs and drug inspectors at state level, which ultimately impacts the Indian population’s access to high quality, appropriate, and safe essential medicines.
Of great concern are approvals for products known as fixed dose combinations, formulations comprised on two or more drugs combined in a fixed ratio of doses and available as a single dose form. In some cases, such as the treatments for HIV and tuberculosis, fixed dose combinations are preferable as they reduce pill burden thus increasing patient adherence to treatment and are more effective than the single entity treatment options. Ideally these treatments are also safer for the patient than having to take multiple treatments separately. However, regardless of whether or not the individual components of combinations have been approved by a country’s regulatory system the fixed dose combination itself is still subject to the stringent regulatory requirements of any medication attempting to seek marketing authorisation and regulatory approval, although to what extent can be quite unclear. This murky area of regulation led the Drug Controller General of India in 2007 to request the withdrawal of 294 fixed dose combinations that were licensed but not approved by the Drug Controller; this issue is still unresolved. A proliferation of fixed dose formulations is problematic and may lead to irrational prescribing and treatment.
In response to such a disclosure, twelve New Drug Approval Committees were established by Central Drugs Standard Control Organisation to give advise on definitions of safety, efficacy and quality and clear guidance on what is required when evaluating new drugs and fixed dose combinations. Each committee currently sets its own requirement for each product under evaluation and committees are still in the process of defining their standards however the workload of the 12 committees is high.
With the knowledge of this ongoing regulatory issue in India, the AMASA project decided to focus on the process of medicine approvals in India, specifically in regards to fixed dose combinations of metformin. First, this work began with an evaluation of the legal framework around the approval of new drugs in India and found that the Rules and Acts currently in place are not adequate. Indeed, a new Drugs and Cosmetics (Amendment) Bill has recently been introduced in the Indian Parliament to create a new Central Drugs Authority, following scathing criticism of the Central Drugs Standard Control Organisation. In order to assist law- and policy-makers, an analysis of new drug approvals over 42 years was undertaken in conjunction with a study of the development of India’s drug laws over seven decades, aiming to assess the extent to which they promote rational regulation of safe and effective allopathic drugs. The Bill would be yet another patch on the old primary Act which has arguably been stretched beyond breaking point. It would do little to address these findings, and does not attempt to provide a rigorous foundation for putting safety, effectiveness, rationality and need at the heart of the country’s drug regulatory system. These oversights should be evaluated before the introduction of a new Central Drugs Authority. Second, in regards to the unbridled proliferation of fixed dose combinations in India, drug approvals, availability, and use of fixed dose combinations of metformin in India were analysed. It was found that irrational production and prescribing of metformin fixed dose combinations are facilitated by non-transparent application of poorly drafted Rules which conflict with WHO guidelines for the approval of fixed dose combination products. Last, a review of the evidence base of selected metformin fixed dose combinations available in India was completed. The severe lack of available efficacy and safety data would not be sufficient for approval of these treatments. Unfortunately, the Central Drugs Standard Control Organisation does not publish data on medicine application approvals or rejections making it difficult to adequately evaluate the regulatory system for approval of such medicines.
Several recommendations were suggested to improve these apparent limitations to the current regulatory system in regards to approvals of fixed dose combinations. Transparency and accountability of regulatory decisions need to be improved. The Central Drugs Standard Control Organisation should determine how many metformin fixed dose combination brands are necessary to ensures availability and price competition in the market place. Also, the Ministry of Health and Family Welfare should exercise its statutory powers to prohibit the import, manufacture, distribution, and sale of fixed dose combinations or should explain and publish its reasoning for granting approvals.
Another key area of research for the AMASA team was international standards of pharmacovigilance and country-specific reporting of adverse drug reactions. It was found that pharmacovigilance is not working in spite of the creation of a national pharmacovigilance programme. Pharmacists and physicians have low/no awareness of the programmes and there is limited understanding of pharmacovigilance. In any case, the national and state run heath systems and patient information systems are inadequate to support pharmacovigilance. Reporting of adverse drug events reporting by physicians and pharmacists is rare. At one pharmacovigilance centre it was found that there was a reliance on collection of data by a technical assistant who proactively sought out cases on the wards.
South Africa
Production
South Africa had about 94 registered pharmaceutical operations in 2007. The majority of companies were only sales and marketing offices with their research and manufacturing operations taking place in foreign countries. Prior to this, South Africa had considerable production capacity but because of consolidation in the pharmaceutical industry, particularly amongst the innovator multinational firms, and the move towards global “centres of excellence” with respect to manufacturing, many sites have been closed down and/or rendered obsolete. Between 1996 and 2009, the country lost 37 pharmaceutical manufacturing plants with additional plants expected to close in the following years. The contraction of the pharmaceutical manufacturing industry caused an associated reduction in employment in the sector from 16,000 in 1999 to 9,500 in 2007. Today only ten multinational companies have production facilities in South Africa with another six using local companies for contract manufacturing and packaging.
Distribution
South Africa’s National Drug Policy promotes partnership building between public and private sector pharmaceutical providers. In line with this policy, provincial Departments of Health developed different types of interventions, including those involving organisational restructuring, in order to strengthen the pharmaceutical supply chains downstream. Organisational reform at selected points of the medicine supply chain was introduced by the Western Cape Department of Health in order to address several challenges, inter alia, problems with stock availability at the medical depot, the high incidence of chronic diseases and the shortage of pharmaceutical staff. Dispensing of chronic prescriptions issued in the public sector was first outsourced to a private company on a 5-year contract in 2005 with a view to reduce patient waiting times at facilities and to ease pharmacy workload. The service provider, Institutional Pharmacy Management, offered a semi-automated dispensing system, which was less labour intensive than facility-based dispensing and delivered approximately 150,000 packages of chronic medication to facilities where patients collect on designated days. The service was first started in a single sub-district (Cape Metropole) and was later rolled out to a few more sub-districts. In 2010 the tender for dispensing and delivering chronic medicines was awarded to a different company, an outcome that was challenged in court by Institutional Pharmacy Management. Preliminary interviews with key supply chain officials for the AMASA project pointed to problems at the Cape Medical Depot approximately 4 to 5 years ago, with high “dues out” lists (medicines out of stock) due to undisclosed reasons. A change in the management structure at the depot in recent years is thought to have brought a positive turnaround on the availability of stock.
In an attempt to depopulate healthcare facilities, certain districts in the Western Cape have devolved the dispensing of pre-packed chronic medicine packets to community-based workers in community centres (e.g. halls). Patients are obligated to visit the doctor at the healthcare facility every 6 months, however, their monthly medication can be collected off-site by community based workers who are usually supervised by a pharmacist, pharmacist assistant or nurse (various models exist). Some districts offer support services at these non-health sites whereby nurses monitor clinical outcomes (e.g. blood pressure, glucose levels) in addition to supplying medicine parcels. Non-governmental organisations are involved in driving and providing human resource support in some of these initiatives.
Prescription and Consumption
A good health system is crucial in any setting to improve health outcomes, efficiency and provide social and financial risk protection and improved efficiency. In order to achieve this primary health care remains the only effective way of delivering some form of health care to many developing country populations.
South Africa has socio-economic disparities across social classes and some experts have highlighted the possibility of social and economic inequalities being reflected in unequal health outcomes. The Eastern Cape Province is a low resource setting where grants are central to the survival of most households. According to the social security picture provided by the Department of Social Development in the financial year 2004/5 the largest number of grant recipients is in the category of old age pensions, followed by disability and child support grants. Dependency on social grants is mostly a result of the high unemployment rates (approximately 30%).
One of the barriers to access is the cost associated with accessing health services. Inequalities still exist between the urban and rural populations in this region with respect to accessing health and pharmaceutical services. In our study and others conducted in South Africa and neighbouring countries, patients have cited financial problems and not the absence of treatment as the primary reason for not adhering to a regimen or dropping out of a treatment programme. With no financial means, patients cannot afford to travel to collect their medication. Although the issue of costs related with accessing health care is raised in literature, it is not clear exactly how much patients are spending on travel costs in relation to income and what the coping strategies are for poor communities. This is a critical aspect for consideration in planning for delivering chronic services targeted for socially and economically vulnerable groups.
Regulation
In South Africa, pharmaceutical regulation is managed by the Medicines Control Council, in accordance with three objectives of the National Drug Policy of 1996. These are the availability and accessibility of essential drugs to all citizens; the safety, efficacy and quality of drugs; good dispensing and prescribing practices; rational drug use; and the promotion of the concept of individual responsibility for health, preventive care and informed decision making.
Under the National Drug Policy, the Medicines Control Council is responsible for facilitating the harmonization of drug regulation and control in the country through management of drug selection, registration, evaluations and testing; as well as procurement and distribution according to Good Manufacturing Practice criteria. Their main purpose is to ‘safeguard and protect the public through ensuring that all medicines that are sold and used in South Africa are safe, therapeutically effective and consistently meet acceptable standards of quality’.
Capacity Constraints for Medicines Registration
Within these regulatory arrangements, a recent review of the South African pharmaceutical industry found that the drug registration process can take from 24 to 36 months, and that local public producers were concerned about inconsistent drug regulatory requirements with respect to exports. Therefore, the biggest challenge facing the Medicines Control Council at the moment is the lack of human resource capacity; there are not enough evaluators to review the approximately 1200 dossiers for drug approvals submitted per year. The majority of these dossiers are reviewed by external evaluators who are invariably full-time academics with competing priorities. Additionally, the Medicines Control Council does not have the physical space and infrastructure to handle all the documents delivered for each dossier. Systems can definitely be improved and the volume of submissions can be reduced immediately by stopping duplicate submissions. Operations can be streamlined by providing training in-house. Currently, there is no IT infrastructure, which means that an electronic document management system cannot be implemented. Thus, submissions cannot be tracked and crucial time is spent organising submitted dossiers. Challenges are further compounded by industry regulatory staff who often submit dossiers of poor quality due to time pressures imposed by senior management. Consequently, dossiers do not comply with the local guidelines. Also, there is a high turnover of staff in industry regulatory units with a horizontal movement to competitor companies. This often transpires during the lag time between submission and feedback/outcome of a dossier application and, as such, staff often do not benefit from the feedback from the Medicines Control Council, ultimately leading to mistakes being perpetuated in different companies.
In addition, it is difficult to control the consistency (from batch to batch) of an imported medicine since the Medicines Control Council does not have the inspection capacity to ensure that manufacturers, after approval, remain Good Manufacturing Practice compliant. Since foreign manufacturers cannot be easily controlled or accessed, it is difficult to determine if they had changed their active pharmaceutical ingredient supplier and whether they have informed the local applicant. Often active pharmaceutical ingredient suppliers are changed after a product has been registered to reduce cost. This could lead to efficacy problems and even resistance development.
The stringency of medicine registration requirements is directly related to inspection capacity of the regulator. The more you can rely on inspectors and the responsibility of applicants the more you can reduce the registration requirements. This is the case with the US FDA, which is why over the counter products do not have to be registered in the US. This is in line with risk-based Good Manufacturing Practice evaluation in the 21st century. South Africa does not have the inspection capacity to do this and can only rely on the information in the dossier. Thus, the Medicines Control Council must do full evaluation of a dossier. An abbreviated medicines registration process is available for innovator products and is based on prior approvals by stringent regulatory authorities of developed countries with which the Medicines Control Council is aligned, such as the FDA, EMEA, etc., although not many companies have made use of this submission route.
The Medicines Control Council is evaluated by the number of registrations it completes per year, however, this is not necessarily the best metric since the registration of a product is dependent not only on the duration of the review process but also on the quality and completeness of the documentation submitted by the applicant. The Medicines Control Council should perhaps be judged on its work output in terms of the number of first, second, and additional evaluations per dossier, number of rejections, number of amendment applications reviewed, number of inspections performed, etc. With the present staff complement, lack of adequate infrastructure, and other resources, the Medicines Control Council are actually performing relatively well at ensuring that the products on the market are safe, effective and of good quality.
In 2008, an amendment to the Medicines and Related Substances Control Act 101 of 1965 (known as the Medicines Act) was passed by parliament for the establishment of a new medicines regulatory authority, the South African Health Products Regulatory Authority, to replace the current MCC. The amendment to the Act received presidential decree in 2009 but the new structure has yet to be implemented.
Legislative and Regulatory Reform Aimed at Improving Access to Medicine
Prior to 1994, South Africa’s private and public pharmaceutical services were concentrated in urban metropolitan areas where the majority of the country’s middle and upper income citizens lived. South Africa’s National Drug Policy was launched in 1996 and is an expression of the Department of Health’s commitment to “ensure an adequate and reliable supply of safe, cost-effective drugs of acceptable quality to all citizens of South Africa and the rational use of drugs by prescribers, dispensers and consumers”. In line with this policy, regulatory control over medicine pricing, generic substitution, ownership and licensing of pharmacies, prescribing by rural pharmacists and dispensing by doctors and nurses ensued. The post-apartheid National Drug Policy and regulatory interventions were targeted at improving with respect to medicines through equitable distribution of pharmaceutical services and enhanced access to medicines. Therefore, the Director General of Health, after consultation with the South African Pharmacy Council, granted 66 carefully selected rural pharmacists section 22 (A) permits to prescribe certain schedule 3 and 4 medicines (previously limited to authorised prescribers) based on established need for pharmaceutical services in the communities. Regulations made it obligatory for these pharmacists to complete a Primary Care Drug Therapy course with the South African Pharmacy Council. Currently, there is a moratorium on granting any further licences, however existing “section 22(A)” pharmacists continue providing these essential pharmaceutical services to underserved communities. Around the same time, regulations allowing licenced medical practitioners to dispense medicines were introduced with the intention of addressing the pharmaceutical needs in areas where there were no pharmacists. The introduction of pharmacy lay ownership in 2003 was an attempt to address the mal-distribution of community pharmacies in the country, many of which were concentrated in urban areas. However, the opening of the market to corporate and courier pharmacies was met with resistance by independent pharmacy groups at the time.
To control the cost of medicines, the Medicines and Related Substances Control Act 101 of 1965 was amended in 2003 to introduce a transparent pricing system that would include a “single exit price”, the only price at which manufacturers can sell medicines to the private sector. In 2004, regulations were introduced for the replacement of the wholesale and retail mark-up system with a fixed professional fee. The dispensing fee regulations turned out to be a capped fee according to a four-tiered model that was subjected to repeated legal challenges by various pharmaceutical groups who thought it to be inappropriately low, until a final resolution was reached in 2011.
Although more than 80% of South Africans access free primary healthcare services and medicines from public sector clinics and community health centres, some choose to use private community pharmacies where waiting times are shorter and access is easier. The government in currently in the process of developing a National Health Insurance scheme with the dual objective of protecting the poor from financial risks and increased private sector participation and identifies private community pharmacies as additional access points for medicines in combination with public clinics.
Pharmacovigilance
In terms of pharmacovigilance, South Africa, with its huge burden of disease and the world’s largest ARV programme, could potentially be at the forefront of signalling adverse drug reports to the international community. Instead, the safe, long-term use of newer essential medicines, including ARVs, remains poorly monitored in this country. While international safety alerts issued from developed nations greatly benefit less resourced countries, there is an urgent need for active surveillance within the local context to consider unique population factors that influence the safety profile of a drug, inter alia, HIV and TB co-infections, malnutrition, use of traditional medicine and genetic factors.
South Africa has been a full member of the WHO International Drug Monitoring Programme since 1992 and is therefore obligated to share its ADR database with the Uppsala Monitoring Centre. Evidence from the most recent cross-country comparison of post-marketing surveillance, however, shows that SA has not been a consistent contributor to this database. Furthermore, no local or international studies have successfully quantified the recent incidences and/or described the patterns of ADR reporting in South Africa, except to cite “underreporting” of adverse drug reports due to practical constraints at facility level, inter alia, lack of knowledge and skills to identify adverse drug reports, lack of understanding of what should be reported and high workload.
Due to the inadequacy of spontaneous reporting, the burden of disease and the on-going registration of several new ARVs, there has been a need for more focussed surveillance studies. This became the mandate of 2 satellite centres established in 2007, viz., Medunsa Pharmacovigilance centre and the Bloemfontein Pregnancy Registry and Paediatric Monitoring Centre. Evidence suggests that these satellite centres have not been actively engaged in focussed surveillance based on adverse drug reports signals detected through the National Adverse Drug Event Monitoring Centre leading to many provinces and NGOs developing their own pharmacovigilance programmes which do not feed into the national system.
The International Context of Medicines Regulation, Finance, Production and Export as They Affect Imports and Production in Uganda, India, and South Africa
Production and Acquisition of Medicines
Countries can obtain medicines directly through in-country production or by importing them from international pharmaceutical manufacturers. Many developing countries have underdeveloped local production capacities and therefore rely on importation to obtain essential medicines. Some countries have managed to develop a viable and internationally competitive pharmaceutical industry. India in particular has become the primary supplier of generic pharmaceuticals to Africa. International donors, in order to ensure reliable supplies of high quality medicines at the lowest possible price, specify the rules for procurement of medicines at international and national levels through programmes such as the WHO’s Prequalification of Medicines Programme. However, national level procurement structures in developing countries are met with significant challenges in regulatory capacity and financial constraints and find it difficult to keep up with such procurement responsibilities.
Medicines Regulatory System and Policies
Effective regulation is necessary for ensuring access to safe, effective and good quality medicines. International regulatory bodies, such as the United States Food and Drug Administration, the European Medicines Agency, and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, set high regulatory standards to ensure that these standards are maintained for medicines. Many developing countries use these international guidelines to develop their own regulatory systems and policies. However financial constraints and workforce capacity confronted by these countries has made it difficult to maintain these high standards. How the medicines regulatory framework functions within a country contributes significantly to the level of access to safe and effective essential medicines.
Medicines Patents and Trade Regulations
One major concern for the international field of pharmaceuticals is the issue of patents and trade. The World Trade Organization was founded in 1994 to ensure that internationally negotiated trade agreements are effectively implemented and enforced. In 1995 its member states adopted the agreement on Trade Related Intellectual Property Rights (TRIPS), which was aimed at establishing strong minimum standards for intellectual property rights. This has a particular application to pharmaceuticals. Under the agreement all World Trade Organization member countries have to provide product patent protection for all products, including pharmaceuticals, within a specified period. India became fully TRIPS compliant in 2005. However, least developed countries, such as Uganda, were offered an extension until 2016. For India, being the major exporters of generic medicines to many countries in Africa, and other countries with limited production capacities, the TRIPS agreement was seen as a major barrier. Many of these effected countries criticised the somewhat cumbersome provisions in TRIPS. The resulting Doha Declaration from 2001 listed some of the flexibilities, which can be utilized by these countries to provide better access to medicines. Little is known about the impact of the TRIPS agreement with regard to changes in production, regulation, and supply chain of medicines as well as import and export in both developing and developed countries.
Health Systems Funding and Donor Role
Developing countries account for 90% of the global disease burden with only 12% of all health spending. High-income countries spend about a hundred times more on health per capita than low-income countries. This leads to a tremendous gap between developed and developing countries with respect to health spending and health needs, which has tremendous consequences for the health status of the world’s poor. Most poor countries are unable to provide their citizens with a basic package of essential health services. Therefore, most rely on international donors to support their country’s health care systems. Most of this international aid is allocated to disease-specific projects (i.e. vertical programmes) rather than to broad-based investments in health infrastructure, human resources, and community-oriented primary healthcare services.
International Context
This project has been investigating issues in access to medicines from the perspectives of the regulatory system, funding structures, production of pharmaceuticals and the exportation/importation of essential medicines not only within each of the study countries but also how this issues may be influenced by or impact a larger international context. In this regard a few key themes have become worthy of a more in-depth examination. In Uganda, questions around Good Manufacture Practice compliance especially in the context of locally produced pharmaceuticals were seen as key concerns in the procurement safe and high-quality essential medicines for the population. The proliferation of fixed dose combinations, particularly for increasingly important diseases such as diabetes, in India has raised concerns around the regulatory system in India for approving such medicines formulations. In South Africa, human resource capacity, either in the regulatory system or with specific categories of health care professionals, plays a big role in the country’s access to medicines. In all cases international standards exist through the WHO or elsewhere to guide developing countries to achieve minimal acceptable standards of regulatory for their pharmaceutical industries. However, constraints such as funding gaps, access to expertly trained personnel, and general capacity issues in all aspects of medicine use remain serious barriers preventing these countries to achieve these goals.
In addition to this country-specific work the project has embarked on an evaluation of the status of the pharmacovigilance systems in these three countries as compared to internationally acceptable norms set forth by the WHO. In all three countries new programs have been introduced but their implementation has been difficult, as similar barriers exist. This research highlights various deficiencies in these systems in each country having identified a lack of resources as key drivers of this deficit. The major constraints were: insufficient funding, lack of trained staff, and inadequate training programs. The systems require continuous strengthening by which stakeholders should focus on improving their current systems in order to adequately meet, sustain, and improve upon the minimum standards set forth by the WHO. A major challenge for these governments will be to move from reactive approach to pharmacovigliance to a more proactive one.
Overall regulation played a key role in access to medicines in all three of our study countries. Whether it be capacity to comply with internationally-accepted Good Manufacture Practice standards, encourage local production, ensure quality and safety of fixed dose combinations, medicines registration backlogs, or pharmacy distribution, a strong regulatory system is required to ensure access to safe, effective and quality medicines.
A Comparative Evaluation of Issues in Access to Medicines Cross-Nationally and Problems in Assuring Full and Appropriate Medicine Accessibility in Uganda, India, and South Africa
Key Findings from Pharmacy Surveys
Uganda
In Uganda, we found some variation in the six medicines in respect to regulation, distribution, availability, and access. Three of the study medicines are ‘programme’ medicines (artemisinin-based therapies, lamivudine, and rifampicin) and relate to the control of communicable diseases, while the other three are not affiliated with a national programme (metformin, fluoxetine, and oxytocin) and relate to the management of non-communicable diseases. As with other essential medicines in Uganda, these medicines still face the challenges of poor availability, stockouts, and poor accessibility. The private sector plays a major role in the control and management of diseases such as HIV/AIDS and tuberculosis, with increasing expansion of services accessed through the private facilities, such as rapid diagnostic tests and glucose and blood pressure monitoring among others. The survey analysed brands of study medicines available because with increasing numbers of branded medicines on the pharmaceutical market there are concerns that some of the brands may not be registered by regulatory authorities and yet are still readily available to the consumer. The surveys found high availability of artemisinin-based therapies and relatively high availability of metformin in retail pharmacies and drug shops, especially in the later. Furthermore, availability of some medicines was found to be very poor within the private sector in rural areas. Only a few of the brands on the NDR were present in outlets surveyed, especially lamivudine. The presence of unregistered/unauthorised formulations indicates weak enforcement. Noteworthy that most of the available products were imported from India and locally manufactured products were not common. The findings of this study provide recommendations that the Government of Uganda can implement to increase access to safe and effective essential medicines throughout the private sector in Uganda. Firstly, improve and strengthen the regulation and enforcement of valid licensing of pharmacies and drug shops specifically in respect to the class of drugs being offered. Secondly, review medicine registration procedures within the NDA and ensure the NDR is kept up-to-date and review the need for so many brands. Lastly, investigate the reasons why patients are using the private sector to obtain certain essential medicines (i.e. artemisinin-based combinations and metformin) and what should be done about this.
India
Of the 4 districts, Mumbai had the highest percentage of pharmacies with metformin, fluoxetine, rifampicin and lamivudine available but the lowest percentage for artemisinin-based therapies and oxytocin. Metformin had the highest level of availability with 96.20% (76/79) in urban pharmacies and 84.44% (38/45) in rural pharmacies with overall availability of 91.93% (114/124), which is highest availability of all the study medicines. No significant differences were found in urban and rural regions on the availability of metformin in the study districts. The availability of lamivudine was 4.44% (2/45) at rural pharmacies. This contrasted sharply with the 32.91% (26/79) availability at urban pharmacies and overall availability of 22.58% (28/124), which was lowest of the study medicines. The study found that rifampicin was used in vertical health programmes more than artemisinin and lamivudine. A total of 154 different brands were identified in the 124 pharmacies surveyed of which 60.38% (93/154) were FDCs and 39.61% (61/154) were SDFs. Metformin made up 48.70% (75/154) of the brands with 73.33% (55/75) as FDCs and 26.66% (20/75) as SDFs. There was a great variation in medicine availability in the districts surveyed.
Key Findings from Consumer Surveys
South Africa
These surveys showed how access is interrupted by a combination of health system inefficiencies, non-health sector issues such as transport and infrastructural challenges and poverty which is the reason why many patients cannot afford to pay for costs associated with health care. Poor patients’ inability to cope with transport and other direct and indirect costs associated with accessing medicines remain a key concern for policy makers and threatens clinical outcomes in the event of interrupted treatment cycles. The findings show that affordability can only be addressed effectively if other aspects of access are also addressed. A comparison across the selected study medicines suggests that HIV patients face greater access barriers because in addition to the other barriers, stigma is still pervasive in local communities.
India
Participants in the ART (antiretroviral therapy) and DOTS (directly-observed therapy – short course for TB treatment) programmes were surveyed. Fewer ART (55%) than DOTS patients (96%) reported no concerns in clinics and lack of privacy was a problem only for ART patients (10%). A large majority (88%) obtained drugs from their designated treatment centres, but ART patients reported more difficulties, partly due to stockouts and long waiting times. Family support was reported by 81% in both groups. Significantly more DOTS patients (73%) reported never experiencing barriers to treatment at home (ART: 42%), but more ART (65%) than DOTS patients (36%) hid their treatment at home. Support from providers was reported more frequently reported by DOTS (>94%) than ART patients (>80%), remaining a significant difference after adjusting for sex, age and residence. Overall, these surveys found a large disparity between registered ART and DOTS patients, with the former experiencing greater challenges in the help-seeking process. These challenges have serious implications for the health of HIV-infected patients and in light of increase demand for treatment in TB-HIV cross-referral.
Comparative Evaluation of Access to Medicines Cross-nationally
The findings from the pharmacy and consumer surveys for each country were used to establish a comparison of access to medicines cross-nationally. In all study countries there was variation in the study medicines surveyed in respect to regulation, distribution, and access as well as considerable variation between regions in the availability of the study medicines. Poor availability of study medicines was found in all countries, particularly in rural areas. Lamivudine had low supplies in both Uganda and India. Stockouts of study medicines were reported in all of the study countries, particularly in peripheral clinics. It was found that the private sector plays a major role in providing access to the study medicines in each of the study countries and therefore there exists a need for more effort to be put into programmes which involve a collaboration between public and private health care sectors. Such efforts must include engagement with private clinics and providers beyond private NGOs and include incentives for collaboration to ensure people receive timely and effective treatment. The results of the surveys also demonstrated that further research should to be done on regulation of the private sector and the interrelationships between drug registration and the availability of drugs on market.
The surveys also identified problems in assuring full and appropriate accessibility to essential medicines. All surveyed medicines were more readily available in urban areas compared to rural areas. Stockouts and poor availability were reported in all study countries. Prices of medicines are high, especially in the private sector. In Uganda, there was a lack of availability of vehicles to transport medicine to rural clinics. Furthermore, in some areas within study countries there was poor public transport to clinics and it was determined that patients lack financial resources to pay for transportation and health care. The issue of affordability can only be addressed effectively if other aspects of access are addressed such as transport and infrastructural challenges. Finally, it was found that stigma still remains barrier for HIV patients in local communities in all study countries.
Knowledge Management and Research Capacity Development
Knowledge Management
Knowledge management, including project communication and dissemination, was critical in day-to-day operations throughout the AMASA project. Communication was an essential aspect of the management of this project as it enabled the exchange of knowledge as a significant project output. For all project communication, both internal and external, different types of knowledge were communicated primarily through web-based tools. These activities were essential prerequisites to ensure success of the project and also important for raising the quality and impact of the research findings.
The implementation of different tools and communication channels in project communication was accompanied by several factors. Although they have (i) different cultural backgrounds (live/work in several countries) and (ii) divergent native languages, (iii) diverse education backgrounds (members of diverse faculties) and (iv) varying technical requirements (e.g. available internet bandwidth), all participants of a project worked together on one project, one main topic and use the same language for the communication within the project: English as lingua franca. These circumstances brought about some problems in communication and knowledge transfer, which needed to be solved in order to keep the project going.
The knowledge management approach for the AMASA project included maintenance of a document management system (DMS), which was accessible to all AMASA partners through a secure password-protected configuration. All research activities were documented through this system, whether it is to maintain an up-to-date record of progress in data collection by site or to have ongoing discussions on manuscript drafts with multiple partners. The DMS has been crucial in allowing the partners to keep abreast of activities at other sites and providing management a quick and easy way to obtain an update of ongoing activities at any site. In addition, the project website has been an invaluable tool which has allowed the dissemination of project outputs in an extremely efficient manner.
Research Capacity Development
The scope of these activities included an approach to the study of socio-cultural determinants of pharmaceutical demand, acceptance and use and an approach to relating macro-level policy issues with micro-level analysis of population behaviour. Recognising that required research skills for data collection, management and analysis, and broader skills of knowledge management may not be at the same required level among all partners, the research team assessed research capacity and developed a strategy early in the project that included site visits, workshops, and project-focused trainings to strengthen research capacity through such ongoing support. Seeing as not all AMASA partners are familiar with research based on qualitative methods and approaches to studying power relations, human rights, and participatory processes, a shared understanding of these concepts was required to formulate priorities for investing in the capacity of individual partner organisations. An appropriate combination of generalised and specialised research capacity strengthening was able to meet the needs of the project effectively. Support was provided for such activities as conducting literature reviews, data collection, data analysis, research monitoring, and manuscript drafting.
Research needs and capacity was monitored throughout the project. This ensured that any new research needs that arose as a result of innovative methods were considered with reference to the available research capacity, thereby enabling appropriate support. In this context, research capacity included not only capacity to perform research (i.e. technical research skills) but also the capacity to manage and interpret findings and manage the implications of these findings. Project interests in the socio-cultural context of pharmaceutical use (e.g. the role of gender, livelihood options, vulnerability and resilience) presented both opportunities and challenges for ensuring the practical interpretation and impact of findings. The agenda for capacity building was bidirectional, acknowledging that Northern partners must constantly assess and consider research approaches and methods based on the actual experience of local conditions. The collective effort of Northern and Southern partners was required to interpret findings and effectively consider their implications. Meetings between key stakeholders and AMASA partners was able to identify not only limitations of the research by also opportunities to influence policy decisions locally and develop interventions to improve access to medicines in timely, cost-effective, and equitable ways.
The project also developed research capacity by increasing linkages between partners through scientific exchange based on interpersonal contact and innovative tools for knowledge management. Capacity building opportunities for staff and student exchanges were also made possible throughout the project.
Potential Impact:
Findings from the proposed research will guide health policy decisions concerned with accessibility, affordability, acceptability and the appropriate use of essential medicines in India, Uganda and South Africa, with implications that benefit other developing countries and the work of international agencies. Our focus on HIV/AIDS, malaria, reproductive health, tuberculosis control and mental health addresses high-priority issues that are especially important for low- and middle-income countries. The activities of each of the work packages will generate policy-relevant information about the production, procurement, distribution and consumer use of the study drugs. Work package 6, concerned with knowledge management, will develop and implement innovative strategies to bring the study findings to the attention of policymakers, and show particular ways that findings should guide policy and action.
After identifying barriers to access and ways to address them, and by also limiting misuse of these drugs, the research will contribute to achieving the Millennium Development Goals (MDG). Specifically, MDGs 4, 5 and 6 are directly concerned with child mortality, maternal health, and major diseases of low- and middle-income countries (HIV/AIDS, malaria and TB), respectively. The impact of the research for policy making is enhanced by the dual concern with access and misuse. It is not only important to enable the use of medicines with proven efficacy but also to ensure that they remain efficacious by limiting the development of resistance, particularly important for malaria and TB. Limiting misuse of oxytocin and misoprostol will contribute to maternal health and child survival. Inappropriate use of fluoxetine does not improve health. Contributing to the control of the health problems of direct concern in our choice of study drugs will enhance the capacity of human resources and contribute to MDG 1 (the eradication of extreme hunger poverty and hunger) and MDG 8 (to develop a global partnership for development). Our findings will enable policy makers to bridge the needs arising from a gap between the activities and experience of medicine supply and use, and the intended effects of higher level policy reflected in TRIPS, GMP and other international trade policies, and national health policies in the Global South.
With its concern for ensuring appropriate use of medicines for health problems affecting the poor, the project promotes pro-poor health policymaking, the explicit interest of MDG 1, to alleviate poverty. The project is an interdisciplinary effort that takes into consideration political, sociological, economic, and public health dimensions of health policy. We expect the synergy arising from interactions between European and Southern partners to also facilitate interactions between more effective global and national health policy by taking full advantage of complementary areas of expertise and experience among Northern and Southern partners. MDG 8, and specifically target 8E (“in cooperation with pharmaceutical companies, provide access to affordable essential drugs in developing countries”), the AMASA project has a unique opportunity to engage with pharmaceutical producers, particularly local pharmaceutical producers, to encourage they consider how their business practices impact access to medicine in these specific countries.
In light of these goals the AMASA project hopes to make the following contributions:
• To relate knowledge about global health regulation, which the European partners are better situated to study, and national regulatory policy in the countries of the three Southern partners, best studied in those countries;
• To promote interactions through partnerships that appropriately exploit complementary expertise, and facilitate mutual learning and development;
• To generate a comprehensive account of trade policy for medicines, distribution networks, and user behaviour that will clarify their interrelationship and guide effective policy;
• To clarify the impact of economic policy on access to medicines at the African and Indian study sites;
• To clarify unmet needs for treatment and misuse of medicines among the most vulnerable segments of the populations in the project-study countries, who are typically most seriously affected by the health problems under consideration;
• To generate new explanatory frameworks and models based on empirical data and systematic cross-country comparisons to guide health policymaking at these sites and with broader international public health implications.
By comparing scientific evidence for appropriate use of the study drugs with how they are actually used, findings will inform disease control, planning and development of health systems as product of our Specific International Cooperation Action (SICA) with International Cooperation Partner Countries (ICPCs), as envisioned by the FP7 programme call.
Main Dissemination Activities
The primary dissemination activities which the AMASA project has undertaken to date are two in-country events in India and Uganda, participation in a large, international conference on pharmaceuticals, and an international dissemination event in London.
In-country Dissemination Event – Kampala, Uganda
AMASA partners from MUST and MAK, lead by Paul Waako, presented several AMASA papers based on data collected in Uganda and distributed policy briefs to the high-level audience who attended Uganda’s Pharmaceutical Society launch in Kampala, Uganda, on 28 June 2013. Among the attendants were Dr. Isaac Ezati from the Ministry of Health as the Guest of Honor, Mr. Martin Oteba (MoH, Pharmacy Division), representatives from the National Medical Stores and Star Pharmaceuticals as well as students and teaching staff from MUK, MUST, Kampala International University, and Gulu University. The Uganda Broadcasting Corporation (TV), and the Daily Monitor (newspaper) were the media outlets for this very important event.
In-country Dissemination Event – Delhi, India
Bolstered by AMASA partners from STPH and QMUL, the team from FRCH, lead by Dr Nerges Mistry, presented several papers based on data collected in India and distributed policy briefs to the high-ranking audience. Among the participants were Prof Ranjit Roy Chaudhury (eminent scientist; sits on various government committees including one on FDCs), Anand Grover (lawyer known for this work on the Novartis case), Dr. Urmila Thatte (KEM Hospital in Mumbai; sits on various government committees including one on FDCs), Dr. C M Gulhati (MIMS India), Dr. Mira Shiva (AIDEN; civil society activist who sits on various government committees including FDCs), Mr. Deshpande (retired FDA official), and Mr. Himanshu Kane (patent lawyer from Mumbai). This dissemination meeting and the interviews done with different attendants afterwards contributed substantially to the current report on fixed dose combinations and a new bill proposing a new drug authority. The AMASA activities came at a very timely manner into the recent debates. The Indian telegraph reported about this very successful event.
In-Country Dissemination - South Africa
South Africa has focussed more on relationship building with specific policy-makers and stakeholders relevant to individual papers. One researcher (Henry Leng) presented his findings on medicine registration to a committee set up by the National Department of Health to establish the new regulatory authority, SAHPRA. His findings are relevant to this committee as they strategise on mechanisms to streamline medicine registration procedures and to introduce policy to minimise the effects of industry capture. Another researcher (Kim Ward) presented her paper on the geographical distribution of community pharmacies to the independent community pharmacy association and her findings will provide the supportive evidence in negotiations with the NDOH to change licencing criteria and to introduce rural incentives with a view to promote equitable distribution of pharmacies. Furthermore, she has had several meetings with a major corporate pharmacy group who are keen to support the public sector in the distribution of medicines in rural areas. They would like to develop a business plan using her paper as a background/motivation
International conference
The 5th International Conference on the Pharmaceutical Life Cycle was held in Driebergen, The Netherlands from 02-04 September 2013 and hosted by the University of Amsterdam. This conference took a different approach to presenting research on pharmaceuticals. It utilised a whole system approach where it viewed pharmaceuticals through the various phases of its life, from production down to consumption, from a multi-disciplinary approach. As this conference’s aim was in perfect alignment with the AMASA project objectives many AMASA members submitted abstracts to this conference. In total, nine AMASA abstracts were selected as paper presentations for this conference. It was a huge success and gave AMASA members from all sites a chance to engage with policy makers, academics, and private sector representatives to discuss AMASA’s work.
International Dissemination Event – London, UK
An AMASA dissemination event for international policymakers was held in London on 18 October 2013 and was hosted by QMUL. The event began with opening remarks from Prof Simon Gaskell, President and Principle of QMUL, followed by welcome remarks from Prof Roger Jeffery (UEdin) and Prof Allyson Pollock (QMUL) this dissemination event was entirely successful. During the morning, AMASA project members gave brief presentations on their results of various research areas. The presentations focused on these main topics: regulation of medicines, access to essential medicines, and access in the community and covered a wide range of topics such as civil society, capacity issues, staff shortages, GMP, local pharmaceutical production and consumer barriers to access. A full programme, abstracts from AMASA partner presentations, and biographies of invited speakers and AMASA partners is available on the AMASA website.
Exploitation of Results
The development of the project and our strategy for knowledge management is based on the following premise: notwithstanding the importance of academic impact, social impact with practical benefits for study communities, countries and beyond is also a priority and major motivation for the project. Dissemination of findings in academic journals too often fails to reach policymakers, and the style of such publications may further limit access of policymakers to the potential impact of findings, even when the journals are accessible on-line. Plans for dissemination will include a focus on key stakeholder audiences. The Swiss Tropical and Public Health Institute has extensive experience in the field of knowledge management, and collaborating with all project partners, the STPH developed the project’s dissemination strategy, mindful of the needs of the various stakeholder audiences. The following points are highlights of the approach:
a) Presentation of the project explaining its purpose in a public website;
b) Local meetings with key stakeholders in health policy, other sectors of civil society and government in each of the study countries;
c) Presentations at national and international conferences;
d) Specially tailored open-source materials (such as 4-page policy briefs, articles for magazines that reach policymakers or presentations to policymakers) for national and international health policymakers, to improve needed and appropriate access to medicines in the study countries and beyond;
e) Dissemination of research findings through information networks operating at various levels, such as annual meetings of medical and public health organizations, the Primafamed network in Africa and the Indian Council of Medical Research in India;
f) Submission of research findings to international peer-reviewed journals;
g) Dissemination of research reports and other project outputs on an open section of the website.
List of Websites:
www.amasa-project.eu
Executive summary
The AMASA consortium is a collaboration of partners in Europe, South Asia and Africa investigating the complexity of pharmaceutical supply chains in low- and middle-income counties and their impact on access to essential medicines. This 3-year project received a €3 million grant through the European Commission’s Seventh Framework Programme (FP7). The eight institutions which are involved in the project are: University of Edinburgh (UK), as coordinating institution, University of Ghent (Belgium), Swiss Tropical and Public Health Institute (Switzerland), Mbarara University of Science and Technology (Uganda), Makerere University (Uganda), University of Western Cape (South Africa), Foundation for Research in Community Health (India), and Queen Mary and Westfield College, University of London (UK).
Access to medicines is a key concern of governments, NGOs and citizens around the world. Much of the research carried out in this area, however, investigates barriers to access through the prism of patient or health system variables; i.e. cost, price, availability, tolerance, compliance, distance and user charges. The alternative discourse is grounded in considerations of intellectual property and barriers to pharmaceutical production, distribution and research innovation. These two elements dominate the policy discourses worldwide, but their interplay and the effects of other regulations at national and international levels are under-examined and not well described.
The AMASA project was stimulated by earlier research conducted at the University of Edinburgh under the leadership of Professor Roger Jeffery. This project, entitled Tracing Pharmaceuticals in South Asia (http://www.csas.ed.ac.uk/research_projects/tracing_phramaceuticals) was funded by ESRC-DFID and focused on three pharmaceutical products in India and Nepal and took a whole-system perspective grounded in public health and population approaches to health care and drug delivery. This required an understanding of the clinical evidence base for each drug, and how this evidence plays out in practice when national and international regulations governing production, cost and access are considered. One of the main findings of this research was the need for further investigation of the complex interplay between the regulations that govern pharmaceutical production and delivery in the formal and informal networks of health care in the study countries.
The main aim of the AMASA research project was to investigate how the interplay of patent regimes, pharmaceutical regulation, availability of drug production facilities, health care infrastructure and service provision, and engagement by foreign donors influence appropriate, affordable access to medicines in South Asia and Sub-Saharan Africa. We have mapped patterns of production, distribution, supply and consumption of study medicines within seven health care areas – HIV/AIDS, Malaria, Reproductive Health, Tuberculosis (TB) Control, Mental Health, Pain Management and Diabetes – with specific consideration for the situation our study countries. We have also investigated the strategies and influence of selected Indian producers who are active as exporters, partners in joint ventures, or as direct producers in the selected South Asian and African countries.
The project goes beyond most studies on pharmaceutical policy that focus on only a small aspect of the supply chain whether it is research and development, pricing or patient adherence. In this project, we took a multi-disciplinary approach to incorporate the entire pharmaceutical supply chain from production down to consumption. In order to achieve this ambitious goal, seven study medicines were followed through the supply chain in three different settings: Uganda, South Africa and India.
In addition, as Indian companies invest more and more in production facilities throughout Africa, understanding more about these North-South and South-South partnerships and their associated knowledge and technology transfer policies becomes relevant. India’s approach to patent recognition is seen as a model that should be implemented in other developing countries. The unique perspective of the AMASA project is its ability to shed light on various aspects of these relationships through the lens of our study countries.
The results of the project are being used to provide recommendations on suggested improvements for various points of the supply chain, through a plan of engagement with relevant stakeholders, such as regulatory agencies and training institutions in each of the focus countries. Specifically, we seek to develop and implement a capacity building initiative in drug regulation aimed primarily at personnel associated with their national drug authorities. Analysing the impact of TRIPS, GMP and other aspects of international trade regimes on access to medicines in these countries has allowed us to propose measures to improve the regulatory and training arrangements to enhance access to medicines in the full range of meanings described in the original proposal. We have generated both nationally and internationally targeted reports, workshops, stakeholder meetings, publications, and policy briefs to ensure that the outcomes of the AMASA project will have maximum impact.
Project Context and Objectives:
Access to medicines remains a critical issue for Asia and Africa, with approximately 40% of the African population and 50% of the South East Asian population living without public access to essential medicines according to The World Medicines Situation 2011 published by the WHO. When the World Trade Organization was established and new rules were agreed for the trade-related aspects of intellectual property rights (TRIPS) there was concern that prices and availability of essential medicines for the poor would be compromised. It was feared that the extension of patent rights to countries such as India, where producers of generic medicines had developed low-cost alternatives to some patented medicines, would limit their exports. In the short-term (because of the varying time of compliancy for different countries ranging from 2005 in India to 2016 or longer in many Sub-Saharan African countries), protections were built in. Several agencies (including UNAIDS, the Global Fund, PEPFAR, and the Clinton Foundation) also mobilised to provide alternative sources of funding in low-income countries. These changes and their implications for access to other medicines for the poor, in fields where generic and patented versions of the same or competitive medicines are available, are under-researched and poorly understood.
The World Health Organization’s Inter-Governmental Working Group (IGWG) report was adopted by the Global Health Assembly in May 2008. Element 6 of this report emphasises that “mechanisms to regulate the safety, quality, and efficacy of medicines and other health products coupled with adherence to good manufacturing practices and effective supply chain management, are critical components of a well-functioning health system”, and that international agreements that might impact on these aspects and therefore access to medicines need to be monitored. The WHO supports a number of countries in their drug regulation efforts. More broadly, its pharmacovigilance efforts are carried out by the Uppsala Monitoring Centre located in Uppsala, Sweden, through international drug monitoring services and the tracking of adverse reactions to pharmaceuticals.
Our research relates to several EU agendas which are oriented towards the pursuit of the Millennium Development Goals (MDGs), particularly those concerning maternal mortality, HIV/AIDS, TB, and malaria. These include the EU’s goal of strengthening EU-Africa dialogue through the Sub-Saharan Africa component of the project, as well as promoting knowledge and technology transfer, and increasing the involvement of African scientists in international collaborative science and research and development projects with respect to health, in contribution to the broader economic and social development envisaged in the MDGs. The evidence gathered through this research will contribute to the knowledge base informing the EU’s actions with respect to improving funding systems to fight HIV/AIDS, TB and malaria, and in particular help to assess its goals of appropriate pharmaceutical-related transfer of technology, capacity building, and local production of drugs in developing and least-developed countries. In compliance with Paragraph 7 of the European Parliament 2007 resolution on TRIPS and access to medicines, this research acknowledges the role of broader factors in addition to patent law that impact on access to medicines, such as health system infrastructure, local manufacturing capacities, and the pricing of pharmaceuticals, and will contribute to knowledge regarding the combined impact of these various factors.
This work also promotes the EU’s agenda of Policy Coherence for Development (PCD), in complying with the EU’s research policy of investigating areas of interest for developing countries, particularly through international cooperation. The work of this research effort is compatible with the European and Developing Countries Clinical Trials Partnership (EDCTP), specifically on AIDS TB and malaria, insofar as it promotes networking between partners in the north and the south, and capacity development and building through research partnerships. The UK Department for International Development (DFID), in collaboration with the World Bank and the WHO, launched the Medicines Transparency Alliance (MeTA), whose goal is to “improve access and affordability of medicines for the one third of the world’s population unable to access basic and essential medicines due to high cost or local unavailability”. Our research complements their activities by helping to provide relevant evidence in advance of such an initiative being introduced in the partner countries and by helping to locate these efforts within a wider framework of changes in international relationships.
Project Objectives
An inception workshop was held at the beginning of the project to fine-tune the general research framework around the project objectives and to confirm or modify the preliminary selection of diagnostic areas and specific medicines. The workshop refined the research questions around pharmaceuticals and specifically for the selected medicines, which included seven themes: production and acquisition, regulatory systems and policies, patents and trade issues, health systems funding and donor roles, supply chains and distribution, consumer and community interests, and study medicine evidence base critique. For each of these thematic areas the following research questions and objectives were developed.
Production/Acquisition
The research questions developed for production and/or acquisition of pharmaceuticals were:
• What are the production capacities of selected Asian and African countries with respect to the seven health areas of interest (HIV/AIDS, malaria, reproductive health, TB control, mental health, pain management and diabetes), and the one specified study medicine within each area?
• What is the balance, in each country and pharmaceuticals group, between imports, local production, and exports to other countries?
In each case we considered the different patterns of active pharmaceutical ingredients (APIs) and formulations and the distribution channels for these drugs at the national and regional level. From these research questions on production and acquisition two research objectives were identified: (1) to determine the production capacities in India, South Africa, and Uganda for selected study medicines and (2) to account for production, import, and export of selected study medicines in these specific contexts and internationally.
Medicines Regulatory Systems and Policies
The research questions developed for medicines regulatory systems and policies were:
• What are the national regulatory standards for production, quality control, distribution, and prescribing and dispensing of medicines?
• How are these regulations developed, what are the enforcement mechanisms, how do they work in practice, and what are the capacity issues involved?
• Over the past 10 years, what has been the importance of critical events (such as investigations into counterfeit drugs, periods of drug shortages, and/or significant increases in prices) in the development of regulatory control of pharmaceutical production and supply in each study country?
From these research questions on medicines regulatory systems and policies five research objectives were identified: (1) to examine the existing international and national policies and regulations (for production, quality control, distribution, and prescribing of medicines); (2) to describe the existing pharmacovigilance systems in each focus country; (3) to determine how well national policies and practices for production, quality control, and pharmacovigilence conform to best regulatory practices and standards (e.g. Good Manufacturing Practice (GMP); (4) to determine how counterfeit and substandard medicines are identified and dealt with; and (5) to determine how critical events have affected policies and regulations.
Medicines Patents and Trade Regulations
The research questions developed for medicines patents and trade regulations were:
• How are patterns of national and regional pharmaceutical production and supply affected by the TRIPS agreement, the Doha Declaration, and international standards for pharmaceutical production?
• What is the impact of other international regulations (such as the procurement decisions made by international agencies like the Global Fund) and bilateral trade agreements on access to medicines?
From these research questions on medicines patents and trade regulations four research objectives were identified: (1) to determine the existing trade regulations and policy which may impact medicines procurement (including bilateral or individual contracts and protection of commercial interests); (2) to determine the interaction of these regulations with access to medicines; (3) to describe the patent status of a medicine (such as when various formulations of the drug exist that are or are not under patent or in the application of a patent extension to use the drug for a new condition potentially altering access to the medicine to treat the condition coming off patent); and (4) to determine the implications and significance of process and product patents.
Health Systems Funding and Donor Roles in Access to Medicines
The research questions developed for health systems funding and donor roles in access to medicines were:
• At the national and regional levels, how are the relevant delivery systems (in HIV/AIDS, malaria, reproductive health, TB control, mental health, pain management and diabetes) organised, funded, financed, and implemented?
• What are the sources of funding for the health problems treated by the selected study medicines?
• How do these programmes interact with foreign donors and supply of pharmaceutical products and what are the implications for access to medicines?
From these research questions on health systems funding and donor roles in access to medicine three research objectives were identified: (1) to determine relative allocation of funding from international donors and national (public and private) funding for health problems associated with selected study medicines (focusing on specific study medicines where possible); (2) to determine how international and national procurement policies affect national health policy, acquisition, and distribution of selected study medicines; and (3) to determine the extent to which the delivery system of the selected drugs is carried out through the general public health system or through a parallel system (e.g. mission, for-profit and not-for-profit, donor-established, NGOs).
Medicines Supply Chains and Distribution
The research question developed for medicines supply chains and distribution was:
• What is the structure of existing supply chains? How many ‘chains’ are there and how do they overlap?
• What processes are in place for quality control at various levels of supply chains?
• What are the strongest and weakest links in supply chains and what makes them so?
• What commercial interests and incentives affect various steps in supply chains? (e.g. revising the nature of supply chains to eliminate middle men)
From this research question on medicines supply chains and distribution four research objectives were identified: (1) to determine the structure of the existing supply chains and potential complementarities and overlap between them; (2) to investigate the processes and capacity (infrastructure and personnel) of the systems for quality control at each level in the supply chain (eg. removal of expired medicines); (3) to identify and evaluate problem points in the supply chain influencing appropriate availability, quality, and cost; and (4) to identify commercial factors influencing structure and operations of supply chains.
Consumer and Community Interests
The research questions developed for consumer and community interests were:
• What are the effects of higher level policy and supply chains on access and use of medicines by patients?
• How does availability and price of medicines affect access?
• How do poverty, livelihood, gender, resilience strategies, and cultural concepts of illness affect consumption-related behaviour, and in turn, how does medicine consumption affect poverty alleviation?
Special attention was paid to adverse event reporting, drug formularies, inspection, monitoring, and pharmaceutical production. From these research questions on consumer and community interests four research objectives were identified: (1) to determine the availability and price to consumers of selected medicines; (2) to examine relationships of perceived affordability, poverty, livelihood, gender, resilience strategies, and cultural concepts of illness affecting consumption-related behaviour; (3) to determine how medicine consumption affects poverty alleviation; and (4) to compare the consumer views of the seven study medicines in the three study countries.
Medicines Evidence Base
The research question developed for the medicines evidence base was:
• What is the evidence base for use of each of the selected study medicines?
From these research questions on medicines evidence base two research objectives were identified: (1) to critically examine the literature to determine the validity of the research supporting use of the selected medicine for its specified use; and (2) to determine whether if and how off-label use is addressed in the literature for each of the study medicines.
International Perspectives
Additionally, within each of these project objectives, which tend to be more country- and medicine-specific, this research draws upon and extends four international perspectives: (1) the importance of strengthening public health management and health system delivery, pharmacovigilance and surveillance; (2) the Global Commodity Chains approach for pharmaceutical products in low- and middle-income countries; (3) health policy transfer and implementation and its suitability for various settings and situations; and (4) human rights from a global perspective and within the field of health care and the ‘right to health’. The international context of these perspectives was the subject of various cross-country inquiries and subsequent reports.
Project Results:
It was determined early on in the AMASA project that substantial background research was needed in each of the thematic areas described above with specific reference to the three focus countries. Therefore, substantial background research was undertaken and subsequently summary reports were written to determine what information had already been reported through scientific publications, government agencies, or international/national organisations. To accomplish this working groups were organised around these themes (see page 16 of DoW).
Each group performed background research in the specific topic area and provided a summary of the theme both within the national context of the focus countries as well as from an international perspective. A thorough analysis of these reports identified informational gaps in the currently available data. These gaps informed our research methodology and allowed the project to contribute novel data to these specific areas of research within the broader framework of access to medicines to achieve the greatest impact.
General Research Methodology
Work began with the development of a framework under which the project research would be undertaken. This project protocol included individual country plans and was crucial in developing the research methodology in which each site would design, collect, analyse, and present data within the project. The final selection of study medicines for each country was based on a number of specific criteria such as ensuring selected medicines are used routinely in study countries and cover a wide range of access and availability issues, limiting the chosen medicines to a manageable number to ensure the best possible research outcomes, allowing for cross-country comparisons, and showcasing different patterns of medicine distribution and use within and across countries. The selected study medicines were as follows:
• lamivudine, used for treating HIV;
• artemisinin-based combination therapies, used for treating malaria;
• oxytocin, used in reproductive health;
• rifampicin, used for treating tuberculosis;
• fluoxetine, used for treating depression;
• fentanyl, used for pain management; and
• metformin, used for treating type 2 diabetes.
Once these study medicines had been selected and the background literature reviews analysed sources of information were identified. Data was collected through semi-structured interviews, surveys, observations, and case studies.
Interviews were conducted with key informants within the specific thematic areas. Interviewees came from a variety of disciplines such as government, international organisations, academia, NGOs. The interview topics were organised in 11 categories: (1) producers (representatives from local pharmaceutical companies, if possible, or multinational companies with local impact); (2) regulators (individuals involved in regulation at the local or national level as well as those with an international perspective); (3) ministry of health (government officials with general knowledge related to the project theme areas or with specific knowledge of the target disease areas or study medicines such as national disease control programme officials); (4) health facility managers (facility managers at various levels of the health care system); (5) prescribers and pharmacists (clinicians of various types, i.e. generalists and specialists, in both the public and private sectors); (6) civil society activists (disease-related advocacy groups, community interest groups, professional and trade associations); (7) patent and trade officials (responsible government officials from national patent and trade offices); (8) distributors (government medical store managers or private distributors at various levels of the supply chain); (9) donor agency representatives (global and country-based key donor organisation officials); (10) community health workers (public sector health workers within health centres or clinics at the local level); and (11) consumers (individuals using the study medicines through public and private clinics). Interview schedules were developed for each topic with general questions, in order to allow for a cross-country analysis and an international perspective, and country-specific questions in order to provide the required information for national dissemination activities and, therefore, the most impact locally.
Surveys were conducted at private pharmacies and with consumers within the specific context of the selected study medicine. Pharmacy surveys (which also included sampling of ‘drug shops’, as they are referred to in Uganda) included obtaining a list of the specific study medicines available in that particular pharmacy/drug shop on that day which included dosages, formulations and prices, if available. In addition, responsible pharmacists or owners were asked a variety of questions about popular brands, requirement of prescriptions, consumer knowledge and preferences, inspections, supply management, and the issue of counterfeits or substandard medicines. Consumers of the study medicines were asked questions about their disease conditions, what medicines they were taking, where the obtained them, preferences for specific medicines, interactions with health care providers, and if they had any issues obtaining or taking the prescribed medicines.
Facility observations investigated public sector health facilities for medicine availability and storage conditions. The case studies conducted in all countries were primarily concerned with stockouts of the study medicines that occurred during the project or local pharmaceutical production.
It was also necessary to identify the specific locations in each country where the research would be undertaken. Uganda selected four districts (Kampala, Mbarara, Apac, and Bundibugyo) that represented both urban and rural regions of the country and, therefore, different levels of availability of health care services. India also selected four districts (Mumbai, Dhule, Nagpur, and Sangli) but all within one state, Maharashtra, in order to investigate district-level issues related to study medicines all within one administrative area. South Africa chose to compare two provinces (Western Cape and Eastern Cape) based on contrasting health care system functionality within the country.
Pharmaceutical Production, Distribution, Prescription, Consumption, and Regulation in Uganda, India, and South Africa
The background research which was completed by the working groups described above were condensed into country-specific reports on the production, distribution, prescription, consumption, and regulation of pharmaceuticals in each of the focus countries: Uganda, India, and South Africa. These reports provided the necessary background information to support the project methodology in achieving three main country-specific objectives of the AMASA project: (1) to evaluate how the interplay of patent regimens, pharmaceutical regulation, availability of drug production facilities, health care infrastructure and engagement of foreign donors influences affordable access to medicines; (2) to identify multiple approaches for accessing needed affordable and good quality medicines; and (3) to identify approaches for limiting inappropriate and irrational use of the study medicines. Key findings from the AMASA project specific to the individual focus countries are described below.
Uganda
Production
According to the Ugandan Ministry of Health, it is estimated that approximately 85-90% of Uganda’s pharmaceutical products are imported from countries such as India and China. The remainder is produced by a handful of local manufacturing facilities. The market is essentially generic with price being the major determining factor for purchase and use. Medicine supply is acquired through both public and private procurement as well as by NGOs, faith-based organisations and donor agencies which requires an extensive coordination strategy to ensure that all required medicines are made available while minimizing stock outs and expiries. For obtaining essential medicines donor funding has been used to provide treatments for malaria, tuberculosis, and HIV/AIDS through the public sector and vertical programmes which can lead to some over-funded programmes and stockouts in others. As this is not a sustainable means of obtaining sufficient essential medicines some countries, such as Uganda, have begun to invest in local production of pharmaceuticals to increase national self-sufficiency.
At present, five to six large- and six small-scale pharmaceutical manufacturers operate in Uganda whereby only secondary (finished products) and tertiary (packaging and labelling) levels of production occurs. Many of the manufacturing plants that do exist in Uganda, such as Quality Chemicals Industries Limited (QCIL), are joint ventures with foreign companies and rely heavily on foreign investment. It is claimed by the local Ugandan Pharmaceutical Manufacturers Association that these companies, if functioning at full capacity, can meet the demand for many of the essential medicines for Uganda’s population. However, this is not happening in practice because local companies cannot employ economies of scale due to the relatively small local market, high energy cost with frequent power interruptions, competition from more efficient foreign suppliers (particularly India and China) and a lack of access to donor funding largely due to stringent compliance conditions regarding quality assurance attached to these funds. For example, a local production plants, Kampala Pharmaceuticals, was affected by national treatment policy change that cost them a great deal of money and other substantial losses. In addition, many donor agencies require medicine suppliers to be WHO prequalified to be eligible for procurement tendering. This is a significant hurdle for local manufactures but one that some developing countries, such as Uganda, are attempting to overcome. Therefore, the gap between demand and local production capacity still results in a heavy dependency on imports.
In depth interviews were conducted in Uganda with local manufacturers, policy makers, medicine distributors, and officials from the National Drug Authority in order to gain insight into the status of local production of pharmaceuticals. The local manufacture of essential medicines in Uganda is considered a key intervention for sustainable access to medicines. Local manufacture of antimalarial and antiretroviral drugs has gained momentum over the past 10 years. The private sector is playing the leading role, a process catalysed by government incentives and partnerships. Incentives documented include market guarantees from the government that have helped to establish and boost Quality Chemicals. Other incentives include: free land, and facilitation of importation of active ingredients (mainly from China and India). There is a massive transfer of technology into Uganda together with considerable technical assistance and expertise from India. The Quality Chemicals factory passed Good Manufacturing Practice (GMP) inspection by WHO. The existing production line however is not optimally utilized due to small orders, and this is being boosted through exploring new distribution ventures in regional markets such as Rwanda, Congo and southern Sudan. Furthermore, active pharmaceutical ingredients and many excipients are imported, primarily from India and China. The cost of the active pharmaceutical ingredients alone can be over 80% of the production cost. Currently, Quality Chemicals has plans to manufacture active pharmaceutical ingredients for artemisinin-based medicines.
In particular, the AMASA project examined in great detail the Government of Uganda’s position in encouraging local pharmaceutical production through the implementation of its health and industrial policies. This was done through a case study of Quality Chemicals and the processes that led to the establishment of this joint venture between the Government of Uganda and Cipla Limited in India. Specifically, an evaluation of the incentives given by the Government of Uganda for such an enterprise and whether local pharmaceutical production within this context is beneficial for Uganda, if the activities of Quality Chemicals can be replicated in Uganda, and finally, whether Quality Chemicals is a model for Africa was completed. Data was primarily obtained by conducting semi-structured interviews conducted with key informants and was supplemented by a review of the literature, newspaper reports, and relevant government policies. Collected information was evaluated using the WHO local production for public health framework. Although local pharmaceutical production is mentioned in current health and industrial policies in Uganda the implementation plans for these policies do not provide any detail on how local pharmaceutical production could or should contribute to the development of both the health and industrial sectors. Without harmonisation of these policies and the inclusion of incentives to reduce price and availability of locally produced essential medicines it does not appear that such endeavours will improve access to medicine in Uganda.
Distribution
In Uganda, there are various distributors of medicines in operation. The major ones include the National Medical Stores and the Joint Medical Stores that control most of the medicine distribution in the country. There are also various importers and wholesalers, some manufacturers, as well as medicine delivery stores in the districts. Key informant interviews were conducted with representatives from the two large distribution stores as well as a selection of importers and wholesalers. The interviews focused on issues such as: guidelines for selection forecasting, procurement, ordering, stock outs, warehousing and storage, transportation and distribution, the political and administrative regulatory framework, and views on the main challenges. Most distributors organised their businesses with a clear divide between sections dealing with administration, finance, technicalities, marketing, and procurement and distribution. They reported human resource challenges such as inadequate training of staff and limited availability of technically trained people. This was attributed in part to a severe shortage of skilled professionals and high staff turnover. Big businesses were found to employ people with some general sales training but with little specific knowledge about medicines sales. Logistics management was mostly done using automated systems and these systems help in quantification and forecasting for minimum quantities. Uganda’s National Drug Authority regulates distributors and quantities to be imported, based on their registration as either wholesaler or retailer. There was a noted focus of the Uganda’s National Drug Stores to push ergometrine and misoprostol as opposed to the earlier choice of oxytocin for third level health clinics. There was stockpiling of misoprostol whilst at the same time reported oxytocin stock outs for some months.
Prescription and Consumption
The prescription and consumption of six study medicines in Uganda covering malaria (artemether-lumefantrine), tuberculosis (rifampicin), HIV/AIDS (lamividine), depression (fluoxetine), diabetes (metformin) and labour (oxytocin). Prescription of these medicines was dependent on the level of the prescriber within the health system. Lower-level prescribers (nurses/midwives) can prescribe artemether-lumefantrine (typically found under the brand name Coartem) to treat uncomplicated P. falcipirum malaria and oxytocin for the prevention of post-partum haemorrhage. Higher-level prescribers can prescribe five of the study medicines with the exception of fluoxetine, used in the treatment of depression and anxiety disorders, which requires a prescription from a specialist. All prescriptions can be cashed either from private or public sectors. Prescriptions made in public facilities can be cashed privately in private clinics due to stock outs. Private clinics have their own private pharmacies within their clinics. This is the same for public facilities. Most prescribers could not differentiate between originator and generic medicines. Medical representatives greatly influenced some prescribers through incentives given during drug promotions.
Artemether-lumefantrine and was the most prescribed due to the high incidence of malaria in Uganda. Many artemether-lumefantrine brands are circulating in the market but this did not alter the cost of these medicines in some districts, as they remained high and unaffordable. This led to misuse by patients who couldn’t afford a full dose with some families sharing a single dose of artemether-lumefantrine to treat all sick family members. Quinine was the primarily alternative to artemether-lumefantrine for most prescribers. Rifampicin and lamivudine were dispensed by a majority of prescribers especially in Level 3 health centres but were not well described except in combination therapies. Most prescribers complained about the interaction of rifampicin and nevirapine, widely available as a combination antiretrovirals, which can compromise adherence to treatments. For these medicines in particular, supply was not dependable to some health centres and some reported regular stock outs for considerable amounts of time with no substantial or planned remedy or fall back options to purchase emergency stocks. Fluoxetine was not on the essential drug list and so all health centres getting their medicines from the National Medical Stores were supplied with an alternative, amitriptyline. Therefore, the majority of prescribers were unaware about fluoxetine and instead used amitriptyline for treatment of depression. Misoprostol was widely used for post-partum haemorrhage management despite oxytocin being recommended as the first line drug. Preferential use of misoprostol was attributed to ease of use (is administered as a tablet as compared to oxytocin which requires an injection), ease of storage (can be stored at room temperature where oxytocin is temperature-sensitive), and wide availability. Misoprostol was also used for other off-label uses such as induction of labour, abortions, and post-abortion care.
In order to evaluate consumption of the study medicines, consumers of these medicines were surveyed. Many consumers complained of unavailability of drugs at some health facilities, inadequate information on medicines, and experiences of side effects with the study medicines. Lack of money for transport and food during treatment were also reported as major challenges related to treatment with the study medicines. A number of people reported obtaining medicines from pharmacies and drug shops using hospital prescriptions. For most medicines, consumer acceptability depended on perceived efficacy, side effects, and the number of pills required. Consumer demand and/or desire to impress consumers were found to be key influences for prescriptions and dispensing especially among private prescribers.
Regulation
In Uganda, the regulation of medicines is overseen by the National Drug Authority. However, professional councils (i.e. medical, pharmacy, nurses and midwives, and allied health professional councils) play an important role in regulation of medicines through the regulation of professionals involved in handling of medicines at various levels of the health care system. Officials from the National Drug Authority were selected for interviews because of the responsibilities they perform in relation to drug regulation in the country. In addition, representatives from various professional councils were interviewed as well. Interviews on the regulation of pharmaceuticals addressed issues such as: capacity limitations of regulatory agencies (including staff, infrastructure, financial); the main challenges to regulatory activities; enforcement of noncompliance to Good Manufacturing Practice and Good Distribution Practice and other features of regulatory noncompliance; regulation of medicine promotion; differences in regulatory practices between public and private sector operations; changes in regulations and their impact over the past decade or two; drug product reviews; pharmacovigilance activities; and policy operations for counterfeit, fake and substandard medicines.
One of the primary concerns raised during these interviews was an acute shortage of human resource capacity faced by the regulatory sector. This was attributed to a lack of adequate training and a shortage of qualified professionals but also partly due to inadequate funding. There are limited funding opportunities for medicine regulation with the World Health Organization taking the lead through the training of inspectors using the International Accreditation System for Good Manufacturing Practice. It was found that companies pay a lot of money for inspections to be carried out. Fortunately, there is sharing of regulatory information with Kenya, Tanzania, including Good Manufacturing Practice, which can help prevent redundant inspections from being done. It was also established that in addition to the formal Good Manufacturing Practice inspections the Ministry of Health has a parallel system that does joint inspections with the Allied Health Professionals Council, the Medical and Dental Professionals Council, and the Nurses and Midwives Council. In regards to tracking the quality and safety of medicines in the country, the government has established four pharmacovigilance centres in various regions of the country with each centre being responsible for adverse drug reaction monitoring and documentation. However, drug quality surveillance is mostly done during preregistration and no sampling is currently done during inspections. This leaves room for the introduction of counterfeits and substandard medicines to enter the market. Inspectors from the National Drug Authority don’t impound substandard medicines, nor is any form of legal action taken against those responsible. Cases of fake medicines, counterfeits, or operating without licenses, take a long time to be dealt with, with very small fines imposed on those found guilty. Counterfeits and substandard medicines left to enter the market without consequence can have a devastating effect on public health outcomes in the country.
India
Production
The Indian pharmaceutical industry is one of the largest among developing countries with a global market share of over 3% and worth an estimated US$12.6 billion in 2009. The leading 250 companies control 70% of the market with market leaders holding nearly 7% of the market share. India is the world leader in generics production accounting for approximately 22% of the global total. A recent report by KPMG indicates that the Indian pharmaceutical industry consists of 250-300 large to moderate firms with nearly 20,000 small firms. McKinsey & Company reported that with an estimated compounded annual growth rate of 13-14% it will be worth US$55 billion by 2020. Formulations account for most of the pharmaceutical market with bulk drugs, such as active pharmaceutical ingredients, accounting for the rest (less than 20%). Requirements for the majority of bulk drugs and almost all finished products are met within India itself.
The CIMS database indicates that both single drug formulations and fixed dose combinations that include our study medicines are available in the Indian market. For example, rifampicin alone is produced by nearly 30 companies with over 120 different brands. Unfortunately, precise data on drug manufacturing capacity, volumes, actual prices, and sales are not available in the public domain.
Distribution
The medicine distribution system in India includes manufacturers, clearing and forwarding agents, stockists, wholesalers, and retailers. The clearing and forwarding agents are responsible for the storage of medicines coming from the manufactures as well as maintaining a stock of medicines until requested by the stockists eventually ending up in retail shops or hospitals. Overall, the distribution system in India is generally regarded as highly fragmented and supply chain management remains an ongoing problem. A description of the supply chain for each of the study medicines is listed below.
• The distribution of antiretrovirals for treating HIV/AIDS is done through established ART centres. However, limited inspection of stocks can lead to variations in quality due to the presence of spurious drugs or substandard medicines due to medicine expiry or inappropriate storage conditions. In addition, the lack of a centralised supplier database can result in fluctuations in price and quality.
• No specific data was found on the distribution system for artemisinin-based therapies in India although, in theory, it would fall under the procurement and distribution system of the National Vector Bourne Disease Control Programme implemented by the Ministry of Health.
• No specific data was found on the distribution system for oxytocin in India although it is widely available in India; used in both urban and rural settings and can be readily purchased over the counter in local pharmacies. The distribution of heat-sensitive oxytocin to rural regions of India with a potential lack of proper storage conditions and ease of purchase from local pharmacies is cause for concern and should be evaluated by the Ministry of Health and Family Welfare.
• The National TB Control Programme administers treatment programmes for tuberculosis through a central procurement system and over 4 million DOTS centres across the 35 states of India. Primarily, medicines are transported from the manufacturer to Government Medical Stores Depots and then distributed to the local treatment centres via State Drug Stores and district-level depots. The strength of the supply chain management system for rifampicin have been achieved through improvements in the management system which allows for more accurate predictions of use and therefore procurement projections and a centralised system which can transfer buffer stocks easily to depots with medicine shortages. In addition, the increased shelf life of rifampicin has improved medicine quality/stability and reduced medicine expiry and related stockouts. Weaknesses in the rifampicin distribution system come from the lengthly procurement process, lack of an instantaneous response to drug shortages to peripheral facilities, and the issue of the distribution of government procured medicines through private pharmacies.
• No specific data was found on the distribution system for fluoxetine although some information was retrieved regarding the availability of fluoxetine in India. The majority of prescriptions for fluoxetine come from the private sector predominantly in urban settings.
• Metformin should be distributed through the National Programme for Prevention and Control of Diabetes, Cardiovascular Diseases and Stroke however no progress has been made with expanding this programme since a 10-state pilot study was completed in 2008. The majority of prescriptions for metformin come from the private sector.
In relation to the tuberculosis and malaria programmes, the expectations of public health facility staff and the programme staff over the coordination and supply medicines are problematic. This is due to lack of clarity over roles and responsibilities between pharmacists at public health facilities and vertical programme staff. The vertical programmes do not have pharmacists operating effectively at the local facility levels and this limits access when expectations are placed on local public health staff. For the study medicines, four are contained within well-established public health programmes (malaria, tuberculosis, HIV, and maternal health) and provided evidence of adequate systems of distribution and supply as well as rational drug use compared with the less well-established programmes for diabetes and mental health. The national programmes for diabetes and mental health are underdeveloped and access through the public sector is poor. Access to these medicines is mainly through the private sector, which is not free of charge. In addition, the irrational production and distribution and consumption of study medicines was evident, especially for metformin, in the four districts we studied.
Prescription and Consumption
There are no data collected by the government on public and private prescriptions. As a result there are no data on prescribing volumes for any of these study medicines. The absence of routinely collected patient and prescribing data render it impossible to analyse met and unmet need for any of the study medicines associated with national disease control programmes underpinning medicine prescription and use. Given the lack of prescription and consumption data ensuring efficacy and safety of all medicines becomes of the utmost importance. As there was found to be limited evidence of efficacy and safety for some of these study medicines, especially fixed dose combinations for metformin (see subsequent section on regulation), there is a need to review efficacy criteria as part of market approvals.
Regulation
The drug regulatory system of India must cover a vast country of 3,287,240 square kilometres and an immense population of 1.029 billion. The 2011 Indian census found that 70% of the population live in rural areas, further increasing this supervisory challenge. India now ranks 3rd in terms of volume of pharmaceuticals production (10% of global share) and 14th largest by value allowing India to meet 95% of its domestic demands for pharmaceuticals. According to a Ministry of Health and Family Welfare Expert Committee Report from 2003 (knows as the Mashelkar Report), there were 418,411 sales licenses including 253,666 retail licenses and 145,447 wholesale licenses in India. The report also stated that there were 935 drug inspectors to inspect these units. Problems with this system exist. For example, manufacturers submission of periodic safety update reports is incomplete and the reports are not being evaluated by the Central Drugs Standard Control Organisation, India’s national drug regulatory body. Recommendations made by the Mashelkar Report to substantially improve medicine regulation still need to be implemented 10 years later. Furthermore, parliamentary and academic reports have highlighted the widespread production and use in India of ‘irrational’ medicines and questioned the rigour of the underpinning regulatory processes and capacity of the Central Drugs Standard Control Organisation.
Consistent with the Mashelkar Report, the AMASA project uncovered evidence of inadequate resources, poor infrastructure, and insufficient workforce capacity for drug inspectors and quality control labs at State level. This has serious implications for access, safety and quality. There is a lack of freely accessible and publicly available systematic data on manufacturing, sales, and prescribing volumes of marketed products in India. The current data on total number of sales units and regulatory staff in the country is not centrally available on drug regulatory agency websites or in any other literature and no data for production and import or sales volume and value by product and manufacturer for any of study medicines were available. Furthermore, the lack of regulation around Good Distribution Practices previously mentioned limits enforcement of the Drug and Cosmetic Rules regarding transport and storage, which adversely impacts the availability of high quality and safe essential medicines to the population. Overseeing public health in India is the responsibility of state authorities. However, the pharmaceutical industry does not observe state borders nor state public health needs. It establishes and disestablishes in response to state subsidies, land donations, tax breaks, and commercial interests. This conflict between trade and public health makes it difficult for states to respond to the regulatory and public health needs and requirements in a timely fashion. It also impacts on the capacity of quality control labs and drug inspectors at state level, which ultimately impacts the Indian population’s access to high quality, appropriate, and safe essential medicines.
Of great concern are approvals for products known as fixed dose combinations, formulations comprised on two or more drugs combined in a fixed ratio of doses and available as a single dose form. In some cases, such as the treatments for HIV and tuberculosis, fixed dose combinations are preferable as they reduce pill burden thus increasing patient adherence to treatment and are more effective than the single entity treatment options. Ideally these treatments are also safer for the patient than having to take multiple treatments separately. However, regardless of whether or not the individual components of combinations have been approved by a country’s regulatory system the fixed dose combination itself is still subject to the stringent regulatory requirements of any medication attempting to seek marketing authorisation and regulatory approval, although to what extent can be quite unclear. This murky area of regulation led the Drug Controller General of India in 2007 to request the withdrawal of 294 fixed dose combinations that were licensed but not approved by the Drug Controller; this issue is still unresolved. A proliferation of fixed dose formulations is problematic and may lead to irrational prescribing and treatment.
In response to such a disclosure, twelve New Drug Approval Committees were established by Central Drugs Standard Control Organisation to give advise on definitions of safety, efficacy and quality and clear guidance on what is required when evaluating new drugs and fixed dose combinations. Each committee currently sets its own requirement for each product under evaluation and committees are still in the process of defining their standards however the workload of the 12 committees is high.
With the knowledge of this ongoing regulatory issue in India, the AMASA project decided to focus on the process of medicine approvals in India, specifically in regards to fixed dose combinations of metformin. First, this work began with an evaluation of the legal framework around the approval of new drugs in India and found that the Rules and Acts currently in place are not adequate. Indeed, a new Drugs and Cosmetics (Amendment) Bill has recently been introduced in the Indian Parliament to create a new Central Drugs Authority, following scathing criticism of the Central Drugs Standard Control Organisation. In order to assist law- and policy-makers, an analysis of new drug approvals over 42 years was undertaken in conjunction with a study of the development of India’s drug laws over seven decades, aiming to assess the extent to which they promote rational regulation of safe and effective allopathic drugs. The Bill would be yet another patch on the old primary Act which has arguably been stretched beyond breaking point. It would do little to address these findings, and does not attempt to provide a rigorous foundation for putting safety, effectiveness, rationality and need at the heart of the country’s drug regulatory system. These oversights should be evaluated before the introduction of a new Central Drugs Authority. Second, in regards to the unbridled proliferation of fixed dose combinations in India, drug approvals, availability, and use of fixed dose combinations of metformin in India were analysed. It was found that irrational production and prescribing of metformin fixed dose combinations are facilitated by non-transparent application of poorly drafted Rules which conflict with WHO guidelines for the approval of fixed dose combination products. Last, a review of the evidence base of selected metformin fixed dose combinations available in India was completed. The severe lack of available efficacy and safety data would not be sufficient for approval of these treatments. Unfortunately, the Central Drugs Standard Control Organisation does not publish data on medicine application approvals or rejections making it difficult to adequately evaluate the regulatory system for approval of such medicines.
Several recommendations were suggested to improve these apparent limitations to the current regulatory system in regards to approvals of fixed dose combinations. Transparency and accountability of regulatory decisions need to be improved. The Central Drugs Standard Control Organisation should determine how many metformin fixed dose combination brands are necessary to ensures availability and price competition in the market place. Also, the Ministry of Health and Family Welfare should exercise its statutory powers to prohibit the import, manufacture, distribution, and sale of fixed dose combinations or should explain and publish its reasoning for granting approvals.
Another key area of research for the AMASA team was international standards of pharmacovigilance and country-specific reporting of adverse drug reactions. It was found that pharmacovigilance is not working in spite of the creation of a national pharmacovigilance programme. Pharmacists and physicians have low/no awareness of the programmes and there is limited understanding of pharmacovigilance. In any case, the national and state run heath systems and patient information systems are inadequate to support pharmacovigilance. Reporting of adverse drug events reporting by physicians and pharmacists is rare. At one pharmacovigilance centre it was found that there was a reliance on collection of data by a technical assistant who proactively sought out cases on the wards.
South Africa
Production
South Africa had about 94 registered pharmaceutical operations in 2007. The majority of companies were only sales and marketing offices with their research and manufacturing operations taking place in foreign countries. Prior to this, South Africa had considerable production capacity but because of consolidation in the pharmaceutical industry, particularly amongst the innovator multinational firms, and the move towards global “centres of excellence” with respect to manufacturing, many sites have been closed down and/or rendered obsolete. Between 1996 and 2009, the country lost 37 pharmaceutical manufacturing plants with additional plants expected to close in the following years. The contraction of the pharmaceutical manufacturing industry caused an associated reduction in employment in the sector from 16,000 in 1999 to 9,500 in 2007. Today only ten multinational companies have production facilities in South Africa with another six using local companies for contract manufacturing and packaging.
Distribution
South Africa’s National Drug Policy promotes partnership building between public and private sector pharmaceutical providers. In line with this policy, provincial Departments of Health developed different types of interventions, including those involving organisational restructuring, in order to strengthen the pharmaceutical supply chains downstream. Organisational reform at selected points of the medicine supply chain was introduced by the Western Cape Department of Health in order to address several challenges, inter alia, problems with stock availability at the medical depot, the high incidence of chronic diseases and the shortage of pharmaceutical staff. Dispensing of chronic prescriptions issued in the public sector was first outsourced to a private company on a 5-year contract in 2005 with a view to reduce patient waiting times at facilities and to ease pharmacy workload. The service provider, Institutional Pharmacy Management, offered a semi-automated dispensing system, which was less labour intensive than facility-based dispensing and delivered approximately 150,000 packages of chronic medication to facilities where patients collect on designated days. The service was first started in a single sub-district (Cape Metropole) and was later rolled out to a few more sub-districts. In 2010 the tender for dispensing and delivering chronic medicines was awarded to a different company, an outcome that was challenged in court by Institutional Pharmacy Management. Preliminary interviews with key supply chain officials for the AMASA project pointed to problems at the Cape Medical Depot approximately 4 to 5 years ago, with high “dues out” lists (medicines out of stock) due to undisclosed reasons. A change in the management structure at the depot in recent years is thought to have brought a positive turnaround on the availability of stock.
In an attempt to depopulate healthcare facilities, certain districts in the Western Cape have devolved the dispensing of pre-packed chronic medicine packets to community-based workers in community centres (e.g. halls). Patients are obligated to visit the doctor at the healthcare facility every 6 months, however, their monthly medication can be collected off-site by community based workers who are usually supervised by a pharmacist, pharmacist assistant or nurse (various models exist). Some districts offer support services at these non-health sites whereby nurses monitor clinical outcomes (e.g. blood pressure, glucose levels) in addition to supplying medicine parcels. Non-governmental organisations are involved in driving and providing human resource support in some of these initiatives.
Prescription and Consumption
A good health system is crucial in any setting to improve health outcomes, efficiency and provide social and financial risk protection and improved efficiency. In order to achieve this primary health care remains the only effective way of delivering some form of health care to many developing country populations.
South Africa has socio-economic disparities across social classes and some experts have highlighted the possibility of social and economic inequalities being reflected in unequal health outcomes. The Eastern Cape Province is a low resource setting where grants are central to the survival of most households. According to the social security picture provided by the Department of Social Development in the financial year 2004/5 the largest number of grant recipients is in the category of old age pensions, followed by disability and child support grants. Dependency on social grants is mostly a result of the high unemployment rates (approximately 30%).
One of the barriers to access is the cost associated with accessing health services. Inequalities still exist between the urban and rural populations in this region with respect to accessing health and pharmaceutical services. In our study and others conducted in South Africa and neighbouring countries, patients have cited financial problems and not the absence of treatment as the primary reason for not adhering to a regimen or dropping out of a treatment programme. With no financial means, patients cannot afford to travel to collect their medication. Although the issue of costs related with accessing health care is raised in literature, it is not clear exactly how much patients are spending on travel costs in relation to income and what the coping strategies are for poor communities. This is a critical aspect for consideration in planning for delivering chronic services targeted for socially and economically vulnerable groups.
Regulation
In South Africa, pharmaceutical regulation is managed by the Medicines Control Council, in accordance with three objectives of the National Drug Policy of 1996. These are the availability and accessibility of essential drugs to all citizens; the safety, efficacy and quality of drugs; good dispensing and prescribing practices; rational drug use; and the promotion of the concept of individual responsibility for health, preventive care and informed decision making.
Under the National Drug Policy, the Medicines Control Council is responsible for facilitating the harmonization of drug regulation and control in the country through management of drug selection, registration, evaluations and testing; as well as procurement and distribution according to Good Manufacturing Practice criteria. Their main purpose is to ‘safeguard and protect the public through ensuring that all medicines that are sold and used in South Africa are safe, therapeutically effective and consistently meet acceptable standards of quality’.
Capacity Constraints for Medicines Registration
Within these regulatory arrangements, a recent review of the South African pharmaceutical industry found that the drug registration process can take from 24 to 36 months, and that local public producers were concerned about inconsistent drug regulatory requirements with respect to exports. Therefore, the biggest challenge facing the Medicines Control Council at the moment is the lack of human resource capacity; there are not enough evaluators to review the approximately 1200 dossiers for drug approvals submitted per year. The majority of these dossiers are reviewed by external evaluators who are invariably full-time academics with competing priorities. Additionally, the Medicines Control Council does not have the physical space and infrastructure to handle all the documents delivered for each dossier. Systems can definitely be improved and the volume of submissions can be reduced immediately by stopping duplicate submissions. Operations can be streamlined by providing training in-house. Currently, there is no IT infrastructure, which means that an electronic document management system cannot be implemented. Thus, submissions cannot be tracked and crucial time is spent organising submitted dossiers. Challenges are further compounded by industry regulatory staff who often submit dossiers of poor quality due to time pressures imposed by senior management. Consequently, dossiers do not comply with the local guidelines. Also, there is a high turnover of staff in industry regulatory units with a horizontal movement to competitor companies. This often transpires during the lag time between submission and feedback/outcome of a dossier application and, as such, staff often do not benefit from the feedback from the Medicines Control Council, ultimately leading to mistakes being perpetuated in different companies.
In addition, it is difficult to control the consistency (from batch to batch) of an imported medicine since the Medicines Control Council does not have the inspection capacity to ensure that manufacturers, after approval, remain Good Manufacturing Practice compliant. Since foreign manufacturers cannot be easily controlled or accessed, it is difficult to determine if they had changed their active pharmaceutical ingredient supplier and whether they have informed the local applicant. Often active pharmaceutical ingredient suppliers are changed after a product has been registered to reduce cost. This could lead to efficacy problems and even resistance development.
The stringency of medicine registration requirements is directly related to inspection capacity of the regulator. The more you can rely on inspectors and the responsibility of applicants the more you can reduce the registration requirements. This is the case with the US FDA, which is why over the counter products do not have to be registered in the US. This is in line with risk-based Good Manufacturing Practice evaluation in the 21st century. South Africa does not have the inspection capacity to do this and can only rely on the information in the dossier. Thus, the Medicines Control Council must do full evaluation of a dossier. An abbreviated medicines registration process is available for innovator products and is based on prior approvals by stringent regulatory authorities of developed countries with which the Medicines Control Council is aligned, such as the FDA, EMEA, etc., although not many companies have made use of this submission route.
The Medicines Control Council is evaluated by the number of registrations it completes per year, however, this is not necessarily the best metric since the registration of a product is dependent not only on the duration of the review process but also on the quality and completeness of the documentation submitted by the applicant. The Medicines Control Council should perhaps be judged on its work output in terms of the number of first, second, and additional evaluations per dossier, number of rejections, number of amendment applications reviewed, number of inspections performed, etc. With the present staff complement, lack of adequate infrastructure, and other resources, the Medicines Control Council are actually performing relatively well at ensuring that the products on the market are safe, effective and of good quality.
In 2008, an amendment to the Medicines and Related Substances Control Act 101 of 1965 (known as the Medicines Act) was passed by parliament for the establishment of a new medicines regulatory authority, the South African Health Products Regulatory Authority, to replace the current MCC. The amendment to the Act received presidential decree in 2009 but the new structure has yet to be implemented.
Legislative and Regulatory Reform Aimed at Improving Access to Medicine
Prior to 1994, South Africa’s private and public pharmaceutical services were concentrated in urban metropolitan areas where the majority of the country’s middle and upper income citizens lived. South Africa’s National Drug Policy was launched in 1996 and is an expression of the Department of Health’s commitment to “ensure an adequate and reliable supply of safe, cost-effective drugs of acceptable quality to all citizens of South Africa and the rational use of drugs by prescribers, dispensers and consumers”. In line with this policy, regulatory control over medicine pricing, generic substitution, ownership and licensing of pharmacies, prescribing by rural pharmacists and dispensing by doctors and nurses ensued. The post-apartheid National Drug Policy and regulatory interventions were targeted at improving with respect to medicines through equitable distribution of pharmaceutical services and enhanced access to medicines. Therefore, the Director General of Health, after consultation with the South African Pharmacy Council, granted 66 carefully selected rural pharmacists section 22 (A) permits to prescribe certain schedule 3 and 4 medicines (previously limited to authorised prescribers) based on established need for pharmaceutical services in the communities. Regulations made it obligatory for these pharmacists to complete a Primary Care Drug Therapy course with the South African Pharmacy Council. Currently, there is a moratorium on granting any further licences, however existing “section 22(A)” pharmacists continue providing these essential pharmaceutical services to underserved communities. Around the same time, regulations allowing licenced medical practitioners to dispense medicines were introduced with the intention of addressing the pharmaceutical needs in areas where there were no pharmacists. The introduction of pharmacy lay ownership in 2003 was an attempt to address the mal-distribution of community pharmacies in the country, many of which were concentrated in urban areas. However, the opening of the market to corporate and courier pharmacies was met with resistance by independent pharmacy groups at the time.
To control the cost of medicines, the Medicines and Related Substances Control Act 101 of 1965 was amended in 2003 to introduce a transparent pricing system that would include a “single exit price”, the only price at which manufacturers can sell medicines to the private sector. In 2004, regulations were introduced for the replacement of the wholesale and retail mark-up system with a fixed professional fee. The dispensing fee regulations turned out to be a capped fee according to a four-tiered model that was subjected to repeated legal challenges by various pharmaceutical groups who thought it to be inappropriately low, until a final resolution was reached in 2011.
Although more than 80% of South Africans access free primary healthcare services and medicines from public sector clinics and community health centres, some choose to use private community pharmacies where waiting times are shorter and access is easier. The government in currently in the process of developing a National Health Insurance scheme with the dual objective of protecting the poor from financial risks and increased private sector participation and identifies private community pharmacies as additional access points for medicines in combination with public clinics.
Pharmacovigilance
In terms of pharmacovigilance, South Africa, with its huge burden of disease and the world’s largest ARV programme, could potentially be at the forefront of signalling adverse drug reports to the international community. Instead, the safe, long-term use of newer essential medicines, including ARVs, remains poorly monitored in this country. While international safety alerts issued from developed nations greatly benefit less resourced countries, there is an urgent need for active surveillance within the local context to consider unique population factors that influence the safety profile of a drug, inter alia, HIV and TB co-infections, malnutrition, use of traditional medicine and genetic factors.
South Africa has been a full member of the WHO International Drug Monitoring Programme since 1992 and is therefore obligated to share its ADR database with the Uppsala Monitoring Centre. Evidence from the most recent cross-country comparison of post-marketing surveillance, however, shows that SA has not been a consistent contributor to this database. Furthermore, no local or international studies have successfully quantified the recent incidences and/or described the patterns of ADR reporting in South Africa, except to cite “underreporting” of adverse drug reports due to practical constraints at facility level, inter alia, lack of knowledge and skills to identify adverse drug reports, lack of understanding of what should be reported and high workload.
Due to the inadequacy of spontaneous reporting, the burden of disease and the on-going registration of several new ARVs, there has been a need for more focussed surveillance studies. This became the mandate of 2 satellite centres established in 2007, viz., Medunsa Pharmacovigilance centre and the Bloemfontein Pregnancy Registry and Paediatric Monitoring Centre. Evidence suggests that these satellite centres have not been actively engaged in focussed surveillance based on adverse drug reports signals detected through the National Adverse Drug Event Monitoring Centre leading to many provinces and NGOs developing their own pharmacovigilance programmes which do not feed into the national system.
The International Context of Medicines Regulation, Finance, Production and Export as They Affect Imports and Production in Uganda, India, and South Africa
Production and Acquisition of Medicines
Countries can obtain medicines directly through in-country production or by importing them from international pharmaceutical manufacturers. Many developing countries have underdeveloped local production capacities and therefore rely on importation to obtain essential medicines. Some countries have managed to develop a viable and internationally competitive pharmaceutical industry. India in particular has become the primary supplier of generic pharmaceuticals to Africa. International donors, in order to ensure reliable supplies of high quality medicines at the lowest possible price, specify the rules for procurement of medicines at international and national levels through programmes such as the WHO’s Prequalification of Medicines Programme. However, national level procurement structures in developing countries are met with significant challenges in regulatory capacity and financial constraints and find it difficult to keep up with such procurement responsibilities.
Medicines Regulatory System and Policies
Effective regulation is necessary for ensuring access to safe, effective and good quality medicines. International regulatory bodies, such as the United States Food and Drug Administration, the European Medicines Agency, and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, set high regulatory standards to ensure that these standards are maintained for medicines. Many developing countries use these international guidelines to develop their own regulatory systems and policies. However financial constraints and workforce capacity confronted by these countries has made it difficult to maintain these high standards. How the medicines regulatory framework functions within a country contributes significantly to the level of access to safe and effective essential medicines.
Medicines Patents and Trade Regulations
One major concern for the international field of pharmaceuticals is the issue of patents and trade. The World Trade Organization was founded in 1994 to ensure that internationally negotiated trade agreements are effectively implemented and enforced. In 1995 its member states adopted the agreement on Trade Related Intellectual Property Rights (TRIPS), which was aimed at establishing strong minimum standards for intellectual property rights. This has a particular application to pharmaceuticals. Under the agreement all World Trade Organization member countries have to provide product patent protection for all products, including pharmaceuticals, within a specified period. India became fully TRIPS compliant in 2005. However, least developed countries, such as Uganda, were offered an extension until 2016. For India, being the major exporters of generic medicines to many countries in Africa, and other countries with limited production capacities, the TRIPS agreement was seen as a major barrier. Many of these effected countries criticised the somewhat cumbersome provisions in TRIPS. The resulting Doha Declaration from 2001 listed some of the flexibilities, which can be utilized by these countries to provide better access to medicines. Little is known about the impact of the TRIPS agreement with regard to changes in production, regulation, and supply chain of medicines as well as import and export in both developing and developed countries.
Health Systems Funding and Donor Role
Developing countries account for 90% of the global disease burden with only 12% of all health spending. High-income countries spend about a hundred times more on health per capita than low-income countries. This leads to a tremendous gap between developed and developing countries with respect to health spending and health needs, which has tremendous consequences for the health status of the world’s poor. Most poor countries are unable to provide their citizens with a basic package of essential health services. Therefore, most rely on international donors to support their country’s health care systems. Most of this international aid is allocated to disease-specific projects (i.e. vertical programmes) rather than to broad-based investments in health infrastructure, human resources, and community-oriented primary healthcare services.
International Context
This project has been investigating issues in access to medicines from the perspectives of the regulatory system, funding structures, production of pharmaceuticals and the exportation/importation of essential medicines not only within each of the study countries but also how this issues may be influenced by or impact a larger international context. In this regard a few key themes have become worthy of a more in-depth examination. In Uganda, questions around Good Manufacture Practice compliance especially in the context of locally produced pharmaceuticals were seen as key concerns in the procurement safe and high-quality essential medicines for the population. The proliferation of fixed dose combinations, particularly for increasingly important diseases such as diabetes, in India has raised concerns around the regulatory system in India for approving such medicines formulations. In South Africa, human resource capacity, either in the regulatory system or with specific categories of health care professionals, plays a big role in the country’s access to medicines. In all cases international standards exist through the WHO or elsewhere to guide developing countries to achieve minimal acceptable standards of regulatory for their pharmaceutical industries. However, constraints such as funding gaps, access to expertly trained personnel, and general capacity issues in all aspects of medicine use remain serious barriers preventing these countries to achieve these goals.
In addition to this country-specific work the project has embarked on an evaluation of the status of the pharmacovigilance systems in these three countries as compared to internationally acceptable norms set forth by the WHO. In all three countries new programs have been introduced but their implementation has been difficult, as similar barriers exist. This research highlights various deficiencies in these systems in each country having identified a lack of resources as key drivers of this deficit. The major constraints were: insufficient funding, lack of trained staff, and inadequate training programs. The systems require continuous strengthening by which stakeholders should focus on improving their current systems in order to adequately meet, sustain, and improve upon the minimum standards set forth by the WHO. A major challenge for these governments will be to move from reactive approach to pharmacovigliance to a more proactive one.
Overall regulation played a key role in access to medicines in all three of our study countries. Whether it be capacity to comply with internationally-accepted Good Manufacture Practice standards, encourage local production, ensure quality and safety of fixed dose combinations, medicines registration backlogs, or pharmacy distribution, a strong regulatory system is required to ensure access to safe, effective and quality medicines.
A Comparative Evaluation of Issues in Access to Medicines Cross-Nationally and Problems in Assuring Full and Appropriate Medicine Accessibility in Uganda, India, and South Africa
Key Findings from Pharmacy Surveys
Uganda
In Uganda, we found some variation in the six medicines in respect to regulation, distribution, availability, and access. Three of the study medicines are ‘programme’ medicines (artemisinin-based therapies, lamivudine, and rifampicin) and relate to the control of communicable diseases, while the other three are not affiliated with a national programme (metformin, fluoxetine, and oxytocin) and relate to the management of non-communicable diseases. As with other essential medicines in Uganda, these medicines still face the challenges of poor availability, stockouts, and poor accessibility. The private sector plays a major role in the control and management of diseases such as HIV/AIDS and tuberculosis, with increasing expansion of services accessed through the private facilities, such as rapid diagnostic tests and glucose and blood pressure monitoring among others. The survey analysed brands of study medicines available because with increasing numbers of branded medicines on the pharmaceutical market there are concerns that some of the brands may not be registered by regulatory authorities and yet are still readily available to the consumer. The surveys found high availability of artemisinin-based therapies and relatively high availability of metformin in retail pharmacies and drug shops, especially in the later. Furthermore, availability of some medicines was found to be very poor within the private sector in rural areas. Only a few of the brands on the NDR were present in outlets surveyed, especially lamivudine. The presence of unregistered/unauthorised formulations indicates weak enforcement. Noteworthy that most of the available products were imported from India and locally manufactured products were not common. The findings of this study provide recommendations that the Government of Uganda can implement to increase access to safe and effective essential medicines throughout the private sector in Uganda. Firstly, improve and strengthen the regulation and enforcement of valid licensing of pharmacies and drug shops specifically in respect to the class of drugs being offered. Secondly, review medicine registration procedures within the NDA and ensure the NDR is kept up-to-date and review the need for so many brands. Lastly, investigate the reasons why patients are using the private sector to obtain certain essential medicines (i.e. artemisinin-based combinations and metformin) and what should be done about this.
India
Of the 4 districts, Mumbai had the highest percentage of pharmacies with metformin, fluoxetine, rifampicin and lamivudine available but the lowest percentage for artemisinin-based therapies and oxytocin. Metformin had the highest level of availability with 96.20% (76/79) in urban pharmacies and 84.44% (38/45) in rural pharmacies with overall availability of 91.93% (114/124), which is highest availability of all the study medicines. No significant differences were found in urban and rural regions on the availability of metformin in the study districts. The availability of lamivudine was 4.44% (2/45) at rural pharmacies. This contrasted sharply with the 32.91% (26/79) availability at urban pharmacies and overall availability of 22.58% (28/124), which was lowest of the study medicines. The study found that rifampicin was used in vertical health programmes more than artemisinin and lamivudine. A total of 154 different brands were identified in the 124 pharmacies surveyed of which 60.38% (93/154) were FDCs and 39.61% (61/154) were SDFs. Metformin made up 48.70% (75/154) of the brands with 73.33% (55/75) as FDCs and 26.66% (20/75) as SDFs. There was a great variation in medicine availability in the districts surveyed.
Key Findings from Consumer Surveys
South Africa
These surveys showed how access is interrupted by a combination of health system inefficiencies, non-health sector issues such as transport and infrastructural challenges and poverty which is the reason why many patients cannot afford to pay for costs associated with health care. Poor patients’ inability to cope with transport and other direct and indirect costs associated with accessing medicines remain a key concern for policy makers and threatens clinical outcomes in the event of interrupted treatment cycles. The findings show that affordability can only be addressed effectively if other aspects of access are also addressed. A comparison across the selected study medicines suggests that HIV patients face greater access barriers because in addition to the other barriers, stigma is still pervasive in local communities.
India
Participants in the ART (antiretroviral therapy) and DOTS (directly-observed therapy – short course for TB treatment) programmes were surveyed. Fewer ART (55%) than DOTS patients (96%) reported no concerns in clinics and lack of privacy was a problem only for ART patients (10%). A large majority (88%) obtained drugs from their designated treatment centres, but ART patients reported more difficulties, partly due to stockouts and long waiting times. Family support was reported by 81% in both groups. Significantly more DOTS patients (73%) reported never experiencing barriers to treatment at home (ART: 42%), but more ART (65%) than DOTS patients (36%) hid their treatment at home. Support from providers was reported more frequently reported by DOTS (>94%) than ART patients (>80%), remaining a significant difference after adjusting for sex, age and residence. Overall, these surveys found a large disparity between registered ART and DOTS patients, with the former experiencing greater challenges in the help-seeking process. These challenges have serious implications for the health of HIV-infected patients and in light of increase demand for treatment in TB-HIV cross-referral.
Comparative Evaluation of Access to Medicines Cross-nationally
The findings from the pharmacy and consumer surveys for each country were used to establish a comparison of access to medicines cross-nationally. In all study countries there was variation in the study medicines surveyed in respect to regulation, distribution, and access as well as considerable variation between regions in the availability of the study medicines. Poor availability of study medicines was found in all countries, particularly in rural areas. Lamivudine had low supplies in both Uganda and India. Stockouts of study medicines were reported in all of the study countries, particularly in peripheral clinics. It was found that the private sector plays a major role in providing access to the study medicines in each of the study countries and therefore there exists a need for more effort to be put into programmes which involve a collaboration between public and private health care sectors. Such efforts must include engagement with private clinics and providers beyond private NGOs and include incentives for collaboration to ensure people receive timely and effective treatment. The results of the surveys also demonstrated that further research should to be done on regulation of the private sector and the interrelationships between drug registration and the availability of drugs on market.
The surveys also identified problems in assuring full and appropriate accessibility to essential medicines. All surveyed medicines were more readily available in urban areas compared to rural areas. Stockouts and poor availability were reported in all study countries. Prices of medicines are high, especially in the private sector. In Uganda, there was a lack of availability of vehicles to transport medicine to rural clinics. Furthermore, in some areas within study countries there was poor public transport to clinics and it was determined that patients lack financial resources to pay for transportation and health care. The issue of affordability can only be addressed effectively if other aspects of access are addressed such as transport and infrastructural challenges. Finally, it was found that stigma still remains barrier for HIV patients in local communities in all study countries.
Knowledge Management and Research Capacity Development
Knowledge Management
Knowledge management, including project communication and dissemination, was critical in day-to-day operations throughout the AMASA project. Communication was an essential aspect of the management of this project as it enabled the exchange of knowledge as a significant project output. For all project communication, both internal and external, different types of knowledge were communicated primarily through web-based tools. These activities were essential prerequisites to ensure success of the project and also important for raising the quality and impact of the research findings.
The implementation of different tools and communication channels in project communication was accompanied by several factors. Although they have (i) different cultural backgrounds (live/work in several countries) and (ii) divergent native languages, (iii) diverse education backgrounds (members of diverse faculties) and (iv) varying technical requirements (e.g. available internet bandwidth), all participants of a project worked together on one project, one main topic and use the same language for the communication within the project: English as lingua franca. These circumstances brought about some problems in communication and knowledge transfer, which needed to be solved in order to keep the project going.
The knowledge management approach for the AMASA project included maintenance of a document management system (DMS), which was accessible to all AMASA partners through a secure password-protected configuration. All research activities were documented through this system, whether it is to maintain an up-to-date record of progress in data collection by site or to have ongoing discussions on manuscript drafts with multiple partners. The DMS has been crucial in allowing the partners to keep abreast of activities at other sites and providing management a quick and easy way to obtain an update of ongoing activities at any site. In addition, the project website has been an invaluable tool which has allowed the dissemination of project outputs in an extremely efficient manner.
Research Capacity Development
The scope of these activities included an approach to the study of socio-cultural determinants of pharmaceutical demand, acceptance and use and an approach to relating macro-level policy issues with micro-level analysis of population behaviour. Recognising that required research skills for data collection, management and analysis, and broader skills of knowledge management may not be at the same required level among all partners, the research team assessed research capacity and developed a strategy early in the project that included site visits, workshops, and project-focused trainings to strengthen research capacity through such ongoing support. Seeing as not all AMASA partners are familiar with research based on qualitative methods and approaches to studying power relations, human rights, and participatory processes, a shared understanding of these concepts was required to formulate priorities for investing in the capacity of individual partner organisations. An appropriate combination of generalised and specialised research capacity strengthening was able to meet the needs of the project effectively. Support was provided for such activities as conducting literature reviews, data collection, data analysis, research monitoring, and manuscript drafting.
Research needs and capacity was monitored throughout the project. This ensured that any new research needs that arose as a result of innovative methods were considered with reference to the available research capacity, thereby enabling appropriate support. In this context, research capacity included not only capacity to perform research (i.e. technical research skills) but also the capacity to manage and interpret findings and manage the implications of these findings. Project interests in the socio-cultural context of pharmaceutical use (e.g. the role of gender, livelihood options, vulnerability and resilience) presented both opportunities and challenges for ensuring the practical interpretation and impact of findings. The agenda for capacity building was bidirectional, acknowledging that Northern partners must constantly assess and consider research approaches and methods based on the actual experience of local conditions. The collective effort of Northern and Southern partners was required to interpret findings and effectively consider their implications. Meetings between key stakeholders and AMASA partners was able to identify not only limitations of the research by also opportunities to influence policy decisions locally and develop interventions to improve access to medicines in timely, cost-effective, and equitable ways.
The project also developed research capacity by increasing linkages between partners through scientific exchange based on interpersonal contact and innovative tools for knowledge management. Capacity building opportunities for staff and student exchanges were also made possible throughout the project.
Potential Impact:
Findings from the proposed research will guide health policy decisions concerned with accessibility, affordability, acceptability and the appropriate use of essential medicines in India, Uganda and South Africa, with implications that benefit other developing countries and the work of international agencies. Our focus on HIV/AIDS, malaria, reproductive health, tuberculosis control and mental health addresses high-priority issues that are especially important for low- and middle-income countries. The activities of each of the work packages will generate policy-relevant information about the production, procurement, distribution and consumer use of the study drugs. Work package 6, concerned with knowledge management, will develop and implement innovative strategies to bring the study findings to the attention of policymakers, and show particular ways that findings should guide policy and action.
After identifying barriers to access and ways to address them, and by also limiting misuse of these drugs, the research will contribute to achieving the Millennium Development Goals (MDG). Specifically, MDGs 4, 5 and 6 are directly concerned with child mortality, maternal health, and major diseases of low- and middle-income countries (HIV/AIDS, malaria and TB), respectively. The impact of the research for policy making is enhanced by the dual concern with access and misuse. It is not only important to enable the use of medicines with proven efficacy but also to ensure that they remain efficacious by limiting the development of resistance, particularly important for malaria and TB. Limiting misuse of oxytocin and misoprostol will contribute to maternal health and child survival. Inappropriate use of fluoxetine does not improve health. Contributing to the control of the health problems of direct concern in our choice of study drugs will enhance the capacity of human resources and contribute to MDG 1 (the eradication of extreme hunger poverty and hunger) and MDG 8 (to develop a global partnership for development). Our findings will enable policy makers to bridge the needs arising from a gap between the activities and experience of medicine supply and use, and the intended effects of higher level policy reflected in TRIPS, GMP and other international trade policies, and national health policies in the Global South.
With its concern for ensuring appropriate use of medicines for health problems affecting the poor, the project promotes pro-poor health policymaking, the explicit interest of MDG 1, to alleviate poverty. The project is an interdisciplinary effort that takes into consideration political, sociological, economic, and public health dimensions of health policy. We expect the synergy arising from interactions between European and Southern partners to also facilitate interactions between more effective global and national health policy by taking full advantage of complementary areas of expertise and experience among Northern and Southern partners. MDG 8, and specifically target 8E (“in cooperation with pharmaceutical companies, provide access to affordable essential drugs in developing countries”), the AMASA project has a unique opportunity to engage with pharmaceutical producers, particularly local pharmaceutical producers, to encourage they consider how their business practices impact access to medicine in these specific countries.
In light of these goals the AMASA project hopes to make the following contributions:
• To relate knowledge about global health regulation, which the European partners are better situated to study, and national regulatory policy in the countries of the three Southern partners, best studied in those countries;
• To promote interactions through partnerships that appropriately exploit complementary expertise, and facilitate mutual learning and development;
• To generate a comprehensive account of trade policy for medicines, distribution networks, and user behaviour that will clarify their interrelationship and guide effective policy;
• To clarify the impact of economic policy on access to medicines at the African and Indian study sites;
• To clarify unmet needs for treatment and misuse of medicines among the most vulnerable segments of the populations in the project-study countries, who are typically most seriously affected by the health problems under consideration;
• To generate new explanatory frameworks and models based on empirical data and systematic cross-country comparisons to guide health policymaking at these sites and with broader international public health implications.
By comparing scientific evidence for appropriate use of the study drugs with how they are actually used, findings will inform disease control, planning and development of health systems as product of our Specific International Cooperation Action (SICA) with International Cooperation Partner Countries (ICPCs), as envisioned by the FP7 programme call.
Main Dissemination Activities
The primary dissemination activities which the AMASA project has undertaken to date are two in-country events in India and Uganda, participation in a large, international conference on pharmaceuticals, and an international dissemination event in London.
In-country Dissemination Event – Kampala, Uganda
AMASA partners from MUST and MAK, lead by Paul Waako, presented several AMASA papers based on data collected in Uganda and distributed policy briefs to the high-level audience who attended Uganda’s Pharmaceutical Society launch in Kampala, Uganda, on 28 June 2013. Among the attendants were Dr. Isaac Ezati from the Ministry of Health as the Guest of Honor, Mr. Martin Oteba (MoH, Pharmacy Division), representatives from the National Medical Stores and Star Pharmaceuticals as well as students and teaching staff from MUK, MUST, Kampala International University, and Gulu University. The Uganda Broadcasting Corporation (TV), and the Daily Monitor (newspaper) were the media outlets for this very important event.
In-country Dissemination Event – Delhi, India
Bolstered by AMASA partners from STPH and QMUL, the team from FRCH, lead by Dr Nerges Mistry, presented several papers based on data collected in India and distributed policy briefs to the high-ranking audience. Among the participants were Prof Ranjit Roy Chaudhury (eminent scientist; sits on various government committees including one on FDCs), Anand Grover (lawyer known for this work on the Novartis case), Dr. Urmila Thatte (KEM Hospital in Mumbai; sits on various government committees including one on FDCs), Dr. C M Gulhati (MIMS India), Dr. Mira Shiva (AIDEN; civil society activist who sits on various government committees including FDCs), Mr. Deshpande (retired FDA official), and Mr. Himanshu Kane (patent lawyer from Mumbai). This dissemination meeting and the interviews done with different attendants afterwards contributed substantially to the current report on fixed dose combinations and a new bill proposing a new drug authority. The AMASA activities came at a very timely manner into the recent debates. The Indian telegraph reported about this very successful event.
In-Country Dissemination - South Africa
South Africa has focussed more on relationship building with specific policy-makers and stakeholders relevant to individual papers. One researcher (Henry Leng) presented his findings on medicine registration to a committee set up by the National Department of Health to establish the new regulatory authority, SAHPRA. His findings are relevant to this committee as they strategise on mechanisms to streamline medicine registration procedures and to introduce policy to minimise the effects of industry capture. Another researcher (Kim Ward) presented her paper on the geographical distribution of community pharmacies to the independent community pharmacy association and her findings will provide the supportive evidence in negotiations with the NDOH to change licencing criteria and to introduce rural incentives with a view to promote equitable distribution of pharmacies. Furthermore, she has had several meetings with a major corporate pharmacy group who are keen to support the public sector in the distribution of medicines in rural areas. They would like to develop a business plan using her paper as a background/motivation
International conference
The 5th International Conference on the Pharmaceutical Life Cycle was held in Driebergen, The Netherlands from 02-04 September 2013 and hosted by the University of Amsterdam. This conference took a different approach to presenting research on pharmaceuticals. It utilised a whole system approach where it viewed pharmaceuticals through the various phases of its life, from production down to consumption, from a multi-disciplinary approach. As this conference’s aim was in perfect alignment with the AMASA project objectives many AMASA members submitted abstracts to this conference. In total, nine AMASA abstracts were selected as paper presentations for this conference. It was a huge success and gave AMASA members from all sites a chance to engage with policy makers, academics, and private sector representatives to discuss AMASA’s work.
International Dissemination Event – London, UK
An AMASA dissemination event for international policymakers was held in London on 18 October 2013 and was hosted by QMUL. The event began with opening remarks from Prof Simon Gaskell, President and Principle of QMUL, followed by welcome remarks from Prof Roger Jeffery (UEdin) and Prof Allyson Pollock (QMUL) this dissemination event was entirely successful. During the morning, AMASA project members gave brief presentations on their results of various research areas. The presentations focused on these main topics: regulation of medicines, access to essential medicines, and access in the community and covered a wide range of topics such as civil society, capacity issues, staff shortages, GMP, local pharmaceutical production and consumer barriers to access. A full programme, abstracts from AMASA partner presentations, and biographies of invited speakers and AMASA partners is available on the AMASA website.
Exploitation of Results
The development of the project and our strategy for knowledge management is based on the following premise: notwithstanding the importance of academic impact, social impact with practical benefits for study communities, countries and beyond is also a priority and major motivation for the project. Dissemination of findings in academic journals too often fails to reach policymakers, and the style of such publications may further limit access of policymakers to the potential impact of findings, even when the journals are accessible on-line. Plans for dissemination will include a focus on key stakeholder audiences. The Swiss Tropical and Public Health Institute has extensive experience in the field of knowledge management, and collaborating with all project partners, the STPH developed the project’s dissemination strategy, mindful of the needs of the various stakeholder audiences. The following points are highlights of the approach:
a) Presentation of the project explaining its purpose in a public website;
b) Local meetings with key stakeholders in health policy, other sectors of civil society and government in each of the study countries;
c) Presentations at national and international conferences;
d) Specially tailored open-source materials (such as 4-page policy briefs, articles for magazines that reach policymakers or presentations to policymakers) for national and international health policymakers, to improve needed and appropriate access to medicines in the study countries and beyond;
e) Dissemination of research findings through information networks operating at various levels, such as annual meetings of medical and public health organizations, the Primafamed network in Africa and the Indian Council of Medical Research in India;
f) Submission of research findings to international peer-reviewed journals;
g) Dissemination of research reports and other project outputs on an open section of the website.
List of Websites:
www.amasa-project.eu
