by Krisana Kraisintu
It is beyond dispute that we are in the midst of a global health crisis. Millions of people around the world, the majority of them living in developing countries, are dying because they lack access to life-saving medications for diseases like AIDS, tuberculosis, and malaria. Cost is a tremendous factor in this crisis.
In 1999 an estimated 1.2 billion people survived on less than one dollar per day, and nearly 2.8 billion on less than two dollars per day. About 90 percent of them live in South or East Asia or Sub-Saharan Africa. As the economic gap between Industrialized and Low Income Countries (LICs) widens, so too is the health gap between rich and poor. This is particularly evident in relation to the HIV/AIDS, tuberculosis and malaria epidemics in Africa. For too long we have accepted the access gap as a fact of life. Twenty eight million people have already died from AIDS and, if things stay as they are, by 2020 the number of deaths will be close to 100 million. Average life span by 2010 will be 27 years in Botswana and Mozambique and in the low 30's in many of their neighboring countries-level not seen since the end of the Nineteenth Century.
Life-saving combination antiretroviral therapy for HIV/AIDS is available-but not to all. During 2001, in high-income countries, 500,000 persons took ARVs and fewer than 25,000 died; in Sub-Saharan Africa, fewer than 30,000 persons took ARVs and 2.2 million die. This huge gap in care has been called a crime against humanity and a holocaust of the poor. It is certainly making us realize that we need to put an end to the global apartheid of poverty and health.
1.Thailand's Experience in Local ARV Production: a Long-term Solution in Implementing Successful ARV Programmes
1.1 HIV/AIDS Situation in Thailand
About 700,000 people are infected with HIV in Thailand, out of a population of 63 million. It is estimated that 2 % of men and 1 % of women are currently living with HIV. There are 30,000 to 50,000 new AIDS and HIV infected patients each year. As a result of successful prevention campaign, the incidence of newly HIV infected has stabilized. Now, Thailand is moving into a more "mature" phase of the epidemic. More and more people are showing symptoms and requiring care. The health care system in Thailand has sufficient resources to treat many common opportunistic infections.
Thailand has experience with antiretroviral therapy since 1988 but the experience has been mixed because of the involved costs and initial poor implementation of treatment in clinical practices.
1.2 Government Pharmaceutical Organization
Government Pharmaceutical Organization (GPO) is a state enterprise under Ministry of Public Health. Its function is to manufacture and supply pharmaceuticals and other medical products to support health services activities of Ministry of Public Health throughout the country.
GPO manufactures more than 300 items of pharmaceuticals especially drugs in the National List of Essential Drugs including biological products. Total number of employee is 2,200 and annual sale volume is about USD 100 million. GPO spends about 1.6% of the sale to research and development.
GPO realizes that one of the factors that is critical for access to antiretroviral drug is affordable prices. Drugs should be available at affordable prices so that they fall within the financial reach of health services and individual in need.
The Research and Development Institute performs basic, applied and pilot scale research which is essential not only to develop new pharmaceutical products but also to compliment and improve existing technologies.
The Research and Development Institute of GPO has been working on the formulation development and bioequivalence studies of HIV/AIDS-related drugs since 1992. Thailand is the first developing country to make generic ARV available in 1995.
In 2001, we invented a fixed-dose generic combination drug known as GPO-VIR, which contains either 30 or 40 mg of stavudine, 150 mg of lamivudine and 200 mg of nevirapine.
This fixed-dose combination will:
At the time, patients receiving this regimen took 6 pills a day at a cost about 85 USD a month for generic drugs and 474 USD for original drugs.
Production of GPO-VIR began in April 2002. Patients take two pills a day at a cost of 27 USD a month, or 324 USD a year. GPO-VIR is now used by about three quarters of the more than 70,000 people being treated for HIV infection in Thailand.
1.2 GPO's Generic Production
Manufacturing of any generic product is possible only after bioequivalence study. All production phases take into consideration the ever more stringent Good Manufacturing Practice (GMP) on manufacturing and quality assurance. GPO now manufactures 6 types of antiretroviral medication in 24 dosage forms, with sufficient production for 100,000 patients. Increased production is planned, as well as a new production facility with improved quality standard.
Attempts to reduce the price from 5 to more than 20 times of its original price depending on the sources of raw materials is now possible due to GPO's generic production of these drugs.
Thailand will achieve the goal of improving affordability through the increase of local production where the costs are lower and quality can be maintained.
2. Technology Transfer for Local Production of HIV/AIDS-related Drugs in African Countries
The Problem of HIV/ AIDS, Tuberculosis and Malaria in Africa
Africa's 785 million people continue to suffer from a huge burden of preventable and treatable disease due to HIV/AIDS, tuberculosis (TB), and Malaria. These diseases cause incalculable human suffering with devastating human and economic impacts.
Today, 38 million people in the world are living with HIV/AIDS, 95% of them in developing countries. While these countries bear the largest burden of HIV infections globally, they account for a very small percentage of the global pharmaceutical market, less than 22% of the anticipated market in 2002.
Although there is no cure for HIV infection, antiretroviral drugs (ARVs) can dramatically reduce HIV-related morbidity and mortality and improve quality of life. The progress that has been made in the global response to AIDS is real-but inadequate. An estimated 1 million people throughout the world are now using antiretroviral medications for HIV infection-double the number who were receiving such treatment two years ago. As of June 2004, 440,000 people from low-and middle-income countries were being treated. About 125,000 were from sub-Saharan Africa, where the burden is the greatest, an increase of 100,000 in two years.
One of the possibilities of increasing access to ARVs is transfer of technology for domestic production. Experiences so far indicate that technology transfer is not widely applied to the African continent. Enabling factors for building local manufacturing capacity through technology transfer are local technical expertise, incentives for mutual technical cooperation, and "warming up" of the local market.
3. Examples of Technology Transfer Projects
3.1 Democratic Republic of Congo
Technology Transfer for Local Production of HIV/AIDS-related Drugs in Democratic Republic of Congo :A Private Entrepreneur with Social Missions in Collaboration with German Medical Aid Organization-action medeor
Pharmakina (PK), originally owned by Boehringer-Mannheim and Roche respectively, has been taken over by the management of PK in the beginning of 1999. PK is not only the largest private employer in Eastern Congo, but also the world's largest producer of quinine. PK has put into operation a diagnostic centre for malaria, tuberculosis and pregnancy tests which is already open to the public. It also operates 12 Health Centres spread over North and South Kivu.
Aim of this humanitarian project is to reduce the morbidity and mortality of AIDS patients in Bukavu, Eastern Congo by offering cost effective diagnosis and low-priced ARV drugs which is a today's best available choice of fixed-dose combination of stavudine, lamivudine and nevirapine and taken as bi-daily tablets. It is well tolerated in most cases, has few contra-indications and is appropriate for use in women of child-bearing age. It has proven efficacy under actual field conditions, is affordable and is easy to take.
This is part of an on-going PPP project (Public Private Partnership) in association with the GTZ (German Agency for Technical Cooperation) that will include the screening, counselling and therapy of patients. A total sum of around US$ 1m will be invested. Production of the HIV/AIDS-related drugs is planned to start in the beginning of 2005.
Action medeor works in close partnership with Pharmakina by providing treatment to a minimum of 50 to 100 patients and monitoring of 250 to 500 patients. It has appointed a project manager who will be responsible for the implementation of antiretroviral therapy. Laboratory has been equipped with flow cytometer and the training of personnel has been provided. Treatment will start when local manufactured drugs are available.
3.2.1 Local Production of HIV/AIDS- related Drugs in Tanzania : Fill in the Gaps of Technical and Human Resources
Of the 33 million people living in Tanzania, an estimated two million people are living with HIV/AIDS. By 2010, AIDS is expected to increase the death rate in Tanzania by more than 50 %, and life expectancy will drop from 65 to 37 years. Nine percent of Tanzania's active labor forces will be HIV-positive by the year 2005. Each year in Tanzania, approximately 50,000 to 60,000 children are born HIV-positive. Some 170,000 Tanzanians living with HIV/AIDS are children under the age 15 and younger.
Currently only one third of the sub-Saharan African countries have capacities for secondary manufacturing. Very often when they do have capacities, they are not in full good manufacturing practices. Today's best available fixed-dose combination of stavudine, lamivudine and nevirapine for which local production capacities are not available in Tanzania. In order to reduce the morbidity and mortality rates among the Tanzania population, the local production of HIV/AIDS-related drugs would provide a long-term solution.
Tanzania Pharmaceutical Industries (TPI), a pharmaceutical manufacturing company, 40 % owned by the government, 60 % by private entrepreneurs, having its operations in Arusha has teamed up to manufacture artemisinin-based antimalarial drugs at affordable prices. Because Tanzania is one of the countries hardest hit by HIV/AIDS, Tanzania has decided to start manufacturing life prolonging drugs for AIDS patients. Since the country has an acute shortage of highly qualified technical and industrial pharmacist, TPI has entered into an agreement with experts from Thailand who have agreed to cooperate and transfer knowledge and know-how and all the necessary information to support the production of pharmaceuticals and in particular antimalarials, antiretrovirals and anti-TB drugs.
3.2.2 Technology Transfer and Local Manufacture of Affordable Antimalarial Drugs in Collaboration with German Medical Aid Organization-action medeor
Thirty to 50% of all African hospital admissions in Africa are due to malaria. Each year, malaria kills between 1 million and 2.7 million people throughout the world, and over 75% of these are African children. Over 85% of these malaria-induced childhood deaths are due to anaemia, low birth weight, and hypoglycaemia. Between 400 and 900 million acute febrile episodes occur annually in African children under the age of 5 living in malaria-endemic regions; this number will double by 2020 if effective treatment and control interventions are not implemented. This is notable because high fevers and febrile convulsions in infants and children can impact brain development, often resulting in impairments in high-order cognitive function with deep implications for children, families, and societies.
As well as a profound impact creating enormous human suffering, the burden of disease due to HIV, TB and malaria in Sub-Saharan Africa stands as a major barrier to economic growth. There is a clearly defined cause-effect relationship between malaria and poverty, so that growth of per capita income from 1965 to 1990 for countries with severe malaria transmission was 0.4% per year, whereas economic growth for countries with fewer malaria infections was 2.3% per year, more than 5 times higher. In short, infectious diseases keep poor people - and their countries - poor. Africa's GDP would have been up to 100 billion US$ greater today if malaria had been eliminated years ago.
Tanzania spends 3.4 % of its Gross National Product on malaria. Each year the fight against malaria costs the country USD 100 million. Thirty percent of the people who go to clinics have malaria. Twenty five percent of the children who die in hospitals, die of malaria.
The objective of this project is the development and implementation of newly formulated antimalarials (Artesunate) with Tanzania Pharmaceutical Industries (TPI) including:
1. The technical backup for TPI in areas of production and system development, such as standard operating procedures
2. The formulation of finished dosage forms
3. Quality improvement and quality assurance
These drugs will be made available by action medeor at low cost for the public health sector.
The newly developed drug name Thaitanzunate was launched officially by Tanzanian Minister of Health in September 2003. The cost of treatment for adults is 0.80 USD. Paediatric dry syrup formulation has been manufactured in May 2004.
Action medeor acts as partner and responsible for the technology transfer and for non-profit procurement in Tanzania. TPI has been audited by action medeor with respect to GMP status.
3.3 Eritrea Economic Viability of Local Production of HIV/AIDS-related Drugs in Eritrea
The HIV/AIDS epidemic is considered to be in its early stages in Eritrea. Compared to other African countries, it has a relatively low HIV prevalence rate of less than 3 percent among adults. Since the first case was reported in Eritrea in 1988, at least 12,000 people in the country have been diagnosed with AIDS and an estimated 60,000-70,000 people are currently living with HIV infection, although many of these may not know their conditions.
Antiretroviral (ARV) drugs which can prolong lives of sufferers, are unavailable in Eritrea. People are forced to buy them from overseas and cost more per month than most people earn in three months. Eritrea is seeking to provide affordable access to ARV drugs for their populations at the most economical costs, but confronted with the fact that prices of patented medicines are too high, wishes to consider implementing policies to promote the use of generic medicines.
Local production or manufacturing of generic versions of patented medicines is a key issue for Eritrean health authorities. Certainly, the ability of a country to maintain local production of essentially needed medicines is a desired objective. The available technological, production and human resource capacities would be key factors in determining the domestic manufacturing capacity.
The most important factor is the economic viability of such local production of ARV drugs, particularly where such production is undertaken as a commercial venture. Whether the production will be sustainable would depend on factors such as the size of the market and the demand for the produced ARV drugs ,as well as the ability to export such medicines.
There are technical and human resources gaps that need to be filled up via technology transfer. Creation of local good manufacturing site capable of receiving the technology transfer represents the best viable and long-term sustainable option for greater access to medicines in African countries. It will also represent the focal point of knowledge and skill oriented society and for a transition into value added manufacturing.
To improve access to essential drugs in Africa, the stimulation of local manufacturing of essential drugs provide a win-win solution to all involved parties and most importantly it represents a viable and sustainable means of tackling the problem at its source.