The Lancet, Volume 354, Number 9193-95, November 27, 1999
By David Wilson, Paul Cawthorne,
Nathan Ford and Saree Aongsonwang
Global trade and access to medicines: AIDS treatments in Thailand
The process of increasing
globalisation is dominated by market influences that have a negative
effect on public health in less-developed countries.1 Laws that govern
the importing of medicines and the patent protection of new discoveries
are subject to an increase in globalisation. The possible effects in
terms of access to medicines are well defined.
In May, 1999,
WHO was given a mandate to monitor the public-health consequences of
international trade agreements.3 Several less-developed countries have
been under pressure from western governments to make changes in trade
laws that would restrict their ability to produce or import drugs
(www.cptech.org, accessed Nov 15, 1999). Non-governmental organisations
have an important part to play in increasing awareness of these issues,
and Mdecins Sans Frontires has been active in bringing these issues
to public attention.
The World Trade Agreements
Trade Agreements, signed in 1994,4 were a decisive step towards a
worldwide free-trade economy. In signing these agreements, member
states of the World Trade Organisation have to abide by several
multilateral agreements, of which the TRIPS agreements (Trade-Related
Aspects of Intellectual Property Rights) probably has the greatest
effect on access to medicines. TRIPS deals with patent law and sets
some minimum standards such as 20-year patent protection for
pharmaceuticals. In certain instances, such as public-health
emergencies or unfair-pricing practices, TRIPS allows for the
production of medicines by companies other than the patent holder
(compulsory licensing). TRIPS also allows for the importing of
medicines from countries other than the country of manufacture
(parallel importing). Compulsory licensing and parallel importing are
both widely practised by western countries. However, some
less-developed countries have been pressured by western governments to
ban compulsory licensing and parallel imports. We focus here on
Thailand, where US trade pressure has limited access to affordable
treatment for patients with HIV and AIDS.
Access to HIV treatment in Thailand
people in Thailand (which has a population of 61 million) are infected
with HIV. In 1995, a World Bank and WHO review advised Thailand to
focus its limited drug resources for HIV on the prevention of perinatal
HIV infection and management of opportunistic infections.5 The Thai
Ministry of Public Health (MOPH) identified the need to formulate a
policy of rational use of antiretroviral drugs6 and issued guidelines
for the clinical management of HIV infection that focused on prevention
and treatment of opportunistic infections.7 Short-course zidovudine to
limit perinatal transmission is to be implemented as a result of a
study by the Centers for Disease Control and Prevention.8 The MOPH also
funds small-scale research projects but these benefit small numbers
only and do not guarantee long-term treatment for participants.9 In
reality few patients can afford antiretroviral treatment. The monthly
price for a course of zidovudine, lamivudine, and indinavir is $US675,
whereas the typical monthly wage of an office-worker is $US120.
Generic drugs in Thailand
legitimate concerns about the quality of therapeutic agents in
less-developed countries. In Thailand, there have recently been reports
of deaths as a result of a new rabies treatment.10 Although a limited
study by UK researchers did not find any pattern of substandard quality
for pharmaceuticals imported from less-developed countries,11 the
researchers commented that improved control at a regulatory level with
less-developed countries is required. A critical assessment of the
extent of the problem is needed.
pharmaceutical industry in Thailand formulates and packages drugs from
imported raw materials. Bioequivalence studies are required for generic
product registration.12 Reports on Thailand's pharmaceutical industry
are available from the website of the UN agency in charge of industrial
development (www.unido.org, accessed Nov 15, 1999. This link creates a new window).
is a key drug in the management of cryptococcal meningitis, an
opportunistic infection that affects one in five patients with AIDS in
Thailand. Until recently, Pfizer was the sole supplier of fluconazole
in Thailand, charging a daily price (dosage of 400 mg) of $US14. In
1998, fluconazole was released from the safety monitoring programme
(the safety monitoring programme confers a period of market
exclusivity) in Thailand and is now supplied by three local
pharmaceutical companies. The price has fallen to 5% of the 1998 price,
which represents a potential annual saving to Thailand of $US3.1
million in the treatment of cryptococcal meningitis. Compliance with
treatment has also improved because more patients can afford the drug.
shows the difference that generic competition can make in terms of
price and accessibility of medicines in less-developed countries.
drugs are cost-effective in a less-developed country.13 Thailand's
Government Pharmaceutical Organisation has supplied generic zidovudine
since 1993. The resulting competition has led to a fall in monthly cost
(600 mg per day) from $US324 in 1992 to $US87 in 1995.
produce other drugs have been less successful, such as the Government
Pharmaceutical Organisation's plan to supply generic didanosine.
Research and development of didanosine was funded by the US National
Institutes of Health and exclusive production rights in the USA were
granted to Bristol-Myers Squibb. The planned production of didanosine
in Thailand was supervised by Bristol-Myers Squibb but buffer
formulation in production was blocked when Bristol-Myers Squibb secured
a product patent for the new formulation in 1998. This company remains
the sole supplier in Thailand selling didanosine at a monthly cost (400
mg per day) of $US136. The agreement between the US National Institute
of Health and Bristol-Myers Squibb includes a reasonable-pricing
clause, which seems to have been overlooked in this case.14 In response
to our requests, the US Department of Health and Human Services has
verbally agreed to review implementation of this clause.
US pressure to change patent law in Thailand
capable of producing good-quality cheap generic drugs, but local
production has been limited by trade pressure from the US government.
government regards TRIPS as a minimum standard, and in bilateral
discussions commonly asks for additional commitments,15 with threats of
trade sanctions to achieve its objectives.16,17 The USA is the
destination of a quarter of exports from Thailand16 so these threats
are taken very seriously.
under threat from the USA to limit textile imports,17 the Thai
government passed a law to introduce product patent protection. As a
safeguard, the Thai government created the Pharmaceutical Patent Review
Board, which had authority to collect economic data, including the
production cost of pharmaceuticals. The US Trade Representative Office
objected18 and in 1998, under threat of increased tariffs on imports of
wood products and jewellery,16 the Pharmaceutical Patent Review Board
was disbanded and measures were taken that led to limiting of the right
to issue compulsory licenses for pharmaceuticals.
The role of WHO
At the World
Health Assembly in May, 1999, WHO was given a mandate to monitor the
public-health consequences of International trade agreements. This new
responsibility is contained within the Revised Drug Strategy, the WHO
policy designed to ensure equitable access to essential drugs and to
good treatment. The Revised Drug Strategy is a comprehensive policy
that addresses all those involved, including member states and
industry. The role of WHO, however, seems to be limited to monitoring
the consequences of the World Trade Organisation agreements such as
TRIPS. This will be of little comfort to countries subjected to
international trade pressure.
adoption of the Revised Drug Strategy, a statement from the Thai
delegation to WHO strongly recommended that the WHO support access to
drugs by actions in areas of technology transfer, local production,
elimination of counterfeit drugs, and human-resource development. The
delegation also identified the need to develop indicators to assess the
positive and negative effects of trade agreements on public health in
less-developed countries. Assessment of the future effect of the
Revised Drug Strategy will not be possible without such indicators.
Nations Development Programme (UNDP) has pointed out that
less-developed countries are merely passive recipients of the effects
of globalisation rather than its beneficiaries,1 and in 1992 and 1998
Thailand responded passively to trade pressure from the USA. However,
the terms of the Revised Drug Strategy require member states to
initiate requests for help; this help is unlikely to have a significant
effect in less-developed countries unless consumer and advocacy groups
pressure governments into action.
the US government has forced Thailand to limit compulsory licensing and
parallel importing, both of which are rights allowed for under TRIPS
and used to great extent by western governments, including the US.15
Other less-developed countries have been subjected to similar pressure,
in particular South Africa (for a list of countries, see
An attempt to
confer to WHO a role in monitoring international trade agreements was
strongly opposed at the 1998 World Health Assembly: US State Department
representatives threatened to withdraw WHO funding when faced with
aggressive WHO support for improved access to patented medicines in
less-developed countries. The adoption by unanimous consensus of the
Revised Drug Strategy this year was, therefore, welcome news.
trade agreements determine what can be done in terms of production and
importation of medicines, so it is important for less-developed
countries to understand fully the implications of these agreements.
Equally, western governments need to receive a more balanced input of
information when formulating trade policies that have public-health
organisations can be more flexible than WHO and have an important part
to play in defending the rights of less-developed countries at local
and internatonal level. Mdecins Sans Frontires has been active as
part of the Thai Non-Governmental Organisation Coalition on AIDS in
bringing trade issues to public attention.21 Similarly, the AIDS
Treatment Action Campaign has done much work in defending South Africa
from US trade pressure. However, it remains to be seen whether WHO and
non-governmental organisations will be able to prevent western trade
pressure from forcing less-developed countries to forego rights to
produce and import medicines that are prohibitively expensive in
1 UNDP. Human Development report. London: United Nations Development Programme, 1999.
2 WHO. Globalization and Access to Drugs: implications of the WTO/TRIPS agreement/WHO/DAP.98.9. Geneva: WHO, 1997.
3 Revised Drug Strategy: Resolution WHO 52.19, 52nd World Health Assembly. Geneva: WHO, 1999.
4 Correa C. The Uruguay round and drugs. Geneva: WHO, 1997.
5 Overview of
satelite symposium 21: formulating national use of antiretrovirals in
Thailand. Proceedings of the Third International Conference on AIDS in
Asia and the Pacific, Chiang Mai, Thailand, Sept 17-21, 1995: 88-98.
C, Phoolcharoen W, Rojanapitayakorn W. The preliminary report on
formulating rational use of anti-retrovirals in Thailand. In: HIV/AIDS
in Thailand 1996: Adults & Pediatrics. Bangkok: Infectious Disease
Association of Thailand, 1996: 82-97.
7 The Thai
Ministry of Public Health. Guidelines for the clinical management of
HIV infection in Children/adults, 5th edn. Nonthaburi: Ministry of
Public Health, 1997.
8 Shaffer N,
Chuachoowong R, Mock PA, et al. Short-course zidovudine for perinatal
HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial.
Lancet 1999; 353: 773-80.
9 Suwanjandee J, Wilson D. Helsinki Declaration and Thailand. Lancet 1999; 354: 343.
T, Mitrabhakdi E, Wilde H, et al. Additional reports of failure to
respond to treatment after rabies exposure in Thailand. Clin Infect Dis
1999; 28: 143-44.
11 Shakoor O,
Taylor R, Behrens R. Assessment of the incidence of substandard drugs
in developing countries. Trop Med Int Health 1997; 2: 839-45.
12 Thai Food
and Drug Administraton. Thai drug system: a situation analysis for
further development. Bangkok: Thai Food and Drug Administration 1995.
13 Lomar A.
Custos directos do tratimento da AIDS no Brasil. Sao Paulo: Fundacao
Insituto de Pesquisas Economica/Ministerio da Saude, 1999.
14 US code of
regulations on exclusive licensing of government owned interventions:
section 404.7. Washington, DC: US Government Printing Office, 1987.
15 US Patent
and Trademark Office. The US Government position on compulsory
licensing of patents. Geneva: US Patent and Trademark Office, 1999.
16 The Economist Intelligence Unit. Thailand Country Report: 2nd Quarter 1998. London: EIU, 1999.
Aongsonwang S. Pharmaceutical patent law: a law by trans-national
companies--Thailand's experience. Paper presented at NGO meeting on
compulsory licensing of essential medical technologies. Geneva: 1999.
18 Office of
the United States Trade Representative national trade estimate report
on foreign trade barriers. Washington DC: US Trade Representative,
19 McGregor A. Compulsory drug licensing for countries hit by HIV is mooted. Lancet 1999; 353: 1165.