SPECIAL
COMMUNICATION
Access to Essential Drugs in Poor Countries
A Lost Battle?
Bernard Pe´coul, MD, MPH
Pierre Chirac, PharmD
Patrice Trouiller, PharmD
Jacques Pinel, PharmD
T
HE EFFECTIVENESS OF DRUGS DE-
pends on a long chain of fac-
tors: research and develop-
ment (R&D) of an appropriate
pharmaceutical agent, production, qual-
ity control, distribution, inventory con-
trol, reliable information for health care
professionals and the general public, di-
agnosis, prescription, financial accessi-
bility, drug dispensing, observance, and
pharmacovigilance. At each level, those
involved may have conflicting interests,
and poor populations are the first to suf-
fer the effects of frail links in this long
chain. Today, entire populations lack ac-
cess to essential quality drugs, and the
situation appears to be deteriorating, fur-
ther marginalizing much of the world’s
population.
Essential drugs are the foundation for
nearly every public health program aimed
at reducing morbidity and mortality in
the developing world, and pharmaceu-
tical expenditure can account for a high
proportion of the total health expendi-
ture of a country. Important health pro-
grams that rely on essential drugs in-
clude child survival programs, antenatal
care, treatment of enteric and respira-
tory pathogens, and control of tubercu-
losis and malaria. Other major public
health issues exist for which there is no
effective pharmaceutical treatment.
This article focuses on 4 main issues
associated with the inaccessibility of
drugs for populations in greatest need:
(1) poor-quality and counterfeit drugs;
(2) lack of availability of essential drugs
due to fluctuating production or prohibi-
tive cost; (3) need to develop field-based
drug research to determine optimum
utilization and remotivate R&D pro-
grams for new drugs for the developing
world; and (4) potential consequences of
the recent World Trade Organization
(WTO) agreements on the availability of
old and new drugs. For all these issues,
practical recommendations to improve
the situation are proposed.
The lack of access to essential drugs
or vaccines because of economic rea-
sons raises new human rights issues in
a world that remains divided among
wealthy countries, developing coun-
tries, and the rest of the world. Yet,
financial access to drugs does not nec-
essarily mean correct use. Continuous
training for health care professionals,
dissemination of reliable pharmacologi-
cal data, and improvement of the man-
agement of drugs are fundamental steps
in improving the quality of care in the
developing world.
THE PROBLEMS
Examples of problems related to devel-
opment and access to drugs and the mag-
nitude of the public health problems con-
cerned are given in TABLE 1.
Counterfeit and
Substandard Products
Drug products must be produced ac-
cording to good manufacturing prac-
tices.
1
Unfortunately, many developing
countries do not have the technical, fi-
nancial, or human resources required for
the application of such standards, and
some developed countries may be less
strict when the product being manufac-
tured is destined for exportation. To-
day, the quality of drugs and, therefore,
their effectiveness and safety are less and
Author Affiliations: Fondation Me´decins Sans Fron-
tie`res, Paris, France.
Corresponding Author and Reprints: Bernard
Pe´coul, MD, MPH, Me´decins Sans Frontie`res,
8 rue St Sabin, 75011 Paris, France (e-mail:
office@paris.msf.org).
Drugs offer a simple, cost-effective solution to many health problems, pro-
vided they are available, affordable, and properly used. However, effective
treatment is lacking in poor countries for many diseases, including African
trypanosomiasis, Shigella dysentery, leishmaniasis, tuberculosis, and bac-
terial meningitis. Treatment may be precluded because no effective drug ex-
ists, it is too expensive, or it has been withdrawn from the market. More-
over, research and development in tropical diseases have come to a near
standstill. This article focuses on the problems of access to quality drugs for
the treatment of diseases that predominantly affect the developing world:
(1) poor-quality and counterfeit drugs; (2) lack of availability of essential
drugs due to fluctuating production or prohibitive cost; (3) need to develop
field-based drug research to determine optimum utilization and remotivate
research and development for new drugs for the developing world; and (4)
potential consequences of recent World Trade Organization agreements on
the availability of old and new drugs. These problems are not independent
and unrelated but are a result of the fundamental nature of the pharmaceu-
tical market and the way it is regulated.
JAMA. 1999;281:361-367 www.jama.com
©1999 American Medical Association. All rights reserved. JAMA, January 27, 1999—Vol 281, No. 4 361
Table 1. 1996 Worldwide Accessibility to Drugs or Vaccines for 10 Diseases
*
Diseases† Deaths†
Incidence (I) or
Prevalence (P)† Drugs or Vaccines Type of Problem
Acute lower respiratory tract
infections
3.9 394 (I) Ceftriaxone sodium (for severe cases
in hospital)
Available but limited use, prohibitive
price
Anti-Haemophilus vaccine (Hib
conjugates Haemophilus)
Available but limited use, prohibitive
price
Antipneumococcal vaccine (group A
streptococci)
Clinical development (phase 1 trial)
Tuberculosis 3.0 7.4 (I) Isoniazid, rifampicin, pyrazinamide,
ethambutol hydrochloride,
streptomycin, thiacetazone
Poor compliance with therapy and
outbreaks of drug-resistant strains
(isoniazid, rifampicin)
Sodium aminosalicylate, ethionamide,
capreomycin sulfate
Production not secured, toxic effects of
drugs
Rifapentine Available but limited use
BCG vaccine Effectiveness disputed
Diarrhea 2.5 4000 (I) Ciprofloxacin (shigellosis) Available but limited use, prohibitive
price
Antirotavirus vaccine Available but limited use, prohibitive
price
Anticholera vaccine (whole cell B) Available but limited use
Anticholera vaccine (103Hgr) Available but limited use
Antishigellosis vaccine Clinical development (phase 2, 3 trials)
Malaria 2.0‡ 300-500 (I) Pyronaridine Clinical development (phase 3 trial)
Artemisinin derivatives Available but production not secured
for substandard products
Coartemether Clinical development (phase 2, 3 trials)
Atovaquone-proguanil Available but limited use
Antimalaria vaccine (preerythrocytic) Clinical development (phase 2, 3 trials)
Antimalaria vaccine (asexual erythrocytic
stage)
Clinical development (phase 2 trial)
Preventable diseases (pertussis,
measles, diphtheria, polio,
tetanus)
1.7 82 (I) Pertussis whole cell, measles, diphtheria,
oral polio, and tetanus vaccines
Substitution of classic formulations by
new formulations, prohibitive price
(eg, acellular pertussis)
Human immunodeficiency virus 1.5 3.1 (I), 22.6 (P) Antiretroviral drugs Available but limited use, prohibitive
price
Anti-HIV vaccines Clinical development (phase 1, 2 trials)
Hepatitis B 1.2 200 (P) Hepatitis B recombinant vaccine Available but limited use
Human African trypanosomiasis 0.15 0.2 (I), 0.3 (P) Suramin sodium Production not secured (no commercial
interest)
Pentamidine isethionate Production not secured (no commercial
interest)
Melarsoprol Production not secured (no commercial
interest)
Eflornithine hydrochloride No longer produced (no commercial
interest)
Leishmaniasis 0.08 2 (I) Meglumine antimoniate Production not secured (no commercial
interest)
Amphotericin B lipid complex Limited use
Aminosidine Old drug (production stopped)
Meningitis 0.04 0.4 (I) Ceftriaxone sodium Available but limited use, prohibitive
price
Oily chloramphenicol Available but production not secured
for substandard products
Antipneumococcal vaccine Clinical development (phase 2, 3 trials)
Anti-Haemophilus vaccine (Hib) Available but limited use, prohibitive
price
Meningococcal A-C conjugates vaccine Clinical development (phase 2 trial)
*For these diseases, there were a total of 16.07 million deaths of 52 million worldwide. One third (17.3 million) were due to infectious diseases (.90% in developing countries).
†Data, in millions, are from the World Health Organization, World Health Statistics Annual, 1996.
17
‡Data indicated in World Health Statistics Annual as 1.8/2.2.
17
ACCESS TO ESSENTIAL DRUGS IN POOR COUNTRIES
362 JAMA, January 27, 1999—Vol 281, No. 4 ©1999 American Medical Association. All rights reserved.
less certain, especially for the poorest
populations, who are attracted by lower-
priced drugs sold outside pharmacies.
Recent years have seen an increase in
the prevalence of counterfeit and sub-
standard drugs on the market. Counter-
feit drugs are those that mimic authen-
tic drugs; substandard drugs are those
produced with little or no attention to
good manufacturing practices.
For example, during the meningitis epi-
demic in Niger in 1995 (41 000 cases re-
ported), Niger authorities organized an ex-
tensive vaccination campaign. In March
1995, Niger received a donation of 88 000
Pasteur Me´rieux and SmithKline Beecham
vaccines from neighboring Nigeria. A
Me´decins Sans Frontie`res (MSF) team
working with local health authorities no-
ticed that the vaccines from Nigeria had
an unusual appearance (eg, difficult re-
constitution, black filaments in the solu-
tion). Inquiries were made and Pasteur
Me´rieux laboratories confirmed that the
batch numbers and expiration dates did
not correspond to their records. The drugs
supplied had been substituted with coun-
terfeit drugs. Tests carried out found no
traces of active product, confirming they
were false. Bottles and labels were cop-
ied to perfection.
2,3
Pasteur Me´rieux sub-
sequently filed a counterfeit suit. Some of
the false vaccines (approximately 28 000)
were located by batch number and de-
stroyed. According to estimates, approxi-
mately 60 000 persons were inoculated
with false vaccines of a total 5 million vac-
cinated during the campaign. Such a pro-
duction would have necessitated an in-
dustrial-scale manufacturing facility, and
it is probable that the 88 000 vaccines
identified as false did not account for the
entire fraudulent production.
Me´decins Sans Frontie`res teams have
encountered similar field examples that
lead to the following conclusions: orga-
nized illegal circuits seem inclined to
manufacture copies with the appearance
of known trademark drugs (counterfeit)
than comparatively less-expensive ge-
neric products, whereas nonorganized il-
legal circuits (small production) increas-
ingly manufacture drugs that are
substandard or inadequate, including ge-
neric drugs.
Poor quality may be accidental, with
no intention to deceive, but oversights
in manufacturing or neglected controls
can have tragic consequences. Such was
the case in recent decades with acetami-
nophen syrups that contained, by mis-
take, a lethal ingredient.
4,5
Fluctuating Production
of Essential Drugs
Drugs necessary for the treatment of cer-
tain tropical diseases have begun to dis-
appear from the market because they are
commercially unprofitable. Many of these
drugs were discovered in the 1950s and
1960s or earlier and are seldom or never
used in wealthy countries.
An example is seen in the effort to treat
epidemic bacterial meningitis, caused by
Neisseria meningitidis, which is rampant
in sub-Saharan Africa. Efficacy of treat-
ment with chloramphenicol in oily sus-
pension (1 intramuscular injection re-
peated after 48 hours) for bacterial
meningitis is comparable with the tra-
ditional treatment with ampicillin (in-
travenous injections 4 times daily for 10
days).
6
The lower cost of chlorampheni-
col in oily suspension—only one tenth
the cost of ampicillin—and its simple ad-
ministration make it particularly suit-
able to the precarious conditions in de-
veloping countries.
6
This is particularly
important during epidemics. In Nigeria
in 1996, for example, more than 100 000
cases of N meningitidis infections were re-
ported.
7
However, production and avail-
ability of chloramphenicol in oily sus-
pension are no longer guaranteed.
Roussel-Uclaf stopped its production in
1995 and transferred its technology to
another laboratory, which began pro-
duction last year. In the meantime, tem-
porary solutions have ensured that a cer-
tain (but far from sufficient) amount of
chloramphenicol is made available.
The circumstances described herein
also apply to other serious illnesses, such
as leishmaniasis and its treatment with
meglumine antimoniate and African try-
panosomiasis and melarsoprol (Table 1).
The trypanocidal activity of eflorni-
thine hydrochloride was discovered in
1985.
8
It is the only treatment proven ef-
fective in cases in which African trypano-
somiasis shows resistance to melarso-
prol, and such resistance is becoming
more frequent (20% in Omungo,
Uganda).
9
This drug was sold at an ex-
tremely high price and is now no longer
manufactured. Only through a joint ef-
fort of the World Health Organization
(WHO), nongovernmental organiza-
tions involved in fieldwork, coopera-
tive bodies, and pharmaceutical compa-
nies could this drug become available and
affordable again.
Prohibitive Costs
The prohibitive cost of antiretroviral
drugs for treatment of people with ac-
quired immunoeficiency syndrome is
well known.
10
There are many other ex-
amples of drugs that are simply not af-
fordable, most of which have been re-
cently marketed and therefore are still
patent-protected.
Shigella dysenteriae type 1 dysentery is
extremely contagious and, without ef-
fective treatment, is lethal in 5% to 15%
of cases.
11
Since 1979, this disease has
been the cause of large epidemics in Af-
rica (for example, in Malawi in 1992 and
1993
12
and in Burundi in 1994
11,13,14
).
Shigella dysenteriae type 1 bacteria quickly
became resistant to traditional treat-
ments. The only effective antibiotic drugs
today are fluoroquinolones (eg, cipro-
floxacin and norfloxacin). However, treat-
ment with these new drugs is 10 times
more expensive than the traditional treat-
ment using nalidixic acid (approxi-
mately $20 vs $2).
15
A special agreement
was reached between Bayer Laboratories
and MSF in 1997 to make available treat-
ments with ciprofloxacin for 50 000
people for a unit price of $2 per treat-
ment. This example shows that it is pos-
sible to find a short-term ad hoc solution
with the pharmaceutical industry, yet no
midterm solution is anticipated.
A recent study of bacterial meningitis
causedby Streptococcus pneumoniaeinchil-
dren aged 2 months to 3 years demon-
strated that use of ceftriaxone sodium
could reduce mortality from 66% to 32%
compared with treatment with chloram-
phenicol in oily suspension.
16
Both anti-
biotics have a sustained action and require
very simple protocols (daily intramuscu-
ACCESS TO ESSENTIAL DRUGS IN POOR COUNTRIES
©1999 American Medical Association. All rights reserved. JAMA, January 27, 1999—Vol 281, No. 4 363
lar injection for a short time) and there-
fore are equally easy to use in adverse con-
ditions. However, ceftriaxone treatment
is 10 times more expensive than chloram-
phenicol treatment.
16
Streptococcus pneu-
moniae infection is also one of the main
causes of severe acute respiratory tract
infections—the primary cause of child
mortality in Africa.
17
Therefore, ceftriax-
one is vital but financially inaccessible to
those populations that need it most.
Prohibitive pricing also extends to pre-
vention when new vaccines are not avail-
able for the population most at risk. For
example, hepatitis B virus and anti-
Haemophilus vaccines are not accessible
because of their steep price. Vaccines for
hepatitis B, a disease predominantly
found in eastern Asia and sub-Saharan
Africa,
18
are approximately 10 times more
expensive than other vaccines included
in the Expanded Programme on Immu-
nization promoted by UNICEF.
19
Essential Drugs Not Adapted
to Field Conditions
Tuberculosis caused the deaths of 3 mil-
lion people in 1997, but the current treat-
ment regimen, known as directly observed
therapy—short course (DOTS), is imprac-
tical and compliance is poor: only 23%
of the world’s population has access to the
WHO tuberculosis control strategy.
20
Research to simplify or shorten the DOTS
regimen is needed to make the treatment
more widely available. Furthermore, the
emergence of strains resistant to com-
monly used antibiotics has potentially dev-
astating worldwide consequences. Cur-
rent second-line treatments are too
expensive, too complex, and too long,
and therefore not realistic for field con-
ditions. Priority should be given to sim-
pler treatment guidelines that combine
several antibiotics, which may not achieve
the same level of efficacy of more com-
plex protocols but are at least more prac-
tical for the field. Today, those with mul-
tidrug-resistant tuberculosis in countries
with limited financial resources are not
receiving treatment, which from a medi-
cal and humanitarian perspective is com-
pletely unacceptable.
Access to drugs for poor populations
would be greatly improved by research
into new forms of existing drugs (eg, sus-
tained action or rectal formulation) and
the development of simpler treatment
guidelines (eg, “one-shot” or short treat-
ments). This type of research cannot be
developed unless technical and finan-
cial resources are made available and,
more importantly, unless new efficacy
criteria are applied to the treatment be-
ing studied.
Insufficient R&D for New Drugs
Increasing drug resistance, adverse
effects, and the lack of feasibility of cur-
rent protocols point to the need for
greater R&D into new drugs for dis-
eases found in the developing world.
From 1910 to 1970, the pharmaceuti-
cal industry’s contribution was crucial
to the fight against endemic tropical
diseases: trypanocides and antiamebic
agents in the 1930s (Bayer, Rhoˆne-
Poulenc), chloroquine during World
War II (Specia, Winthrop), and in the
1960s, the discovery of leading anthel-
mintics (Janssen). Since then, pharma-
ceutical companies have adopted a
completely different strategy.
21
Among the 1223 new chemical enti-
ties commercialized from 1975 to 1997,
379 (30.9%) are considered therapeu-
tic innovations, but only 13 (1%) are spe-
cifically for tropical diseases (TABLE 2).
Two of these 13 drugs are actually up-
dated versions of previous products (new
formulations of pentamidine and am-
photericin B), 2 are the result of mili-
tary research (halofantrine hydrochlo-
ride and mefloquine), 5 come from
veterinary research (albendazole, benz-
nidazole, ivermectin, oxamniquine, and
praziquantel), and only 4 (0.3%) may be
considered direct results of R&D activi-
ties of the pharmaceutical industry (ar-
temether, atovaquone, eflornithine, and
nifurtimox).
22
Thus, it appears that pharmaceutical
R&D is abandoning tropical diseases.
There are 4 main reasons for this shift:
1. Costs and Risks of R&D Rela-
tive to the Low Purchasing Power of
Developing Countries. A typical R&D
program (from initial results to registra-
tion) would cost approximately $160
million and take between 8 and 12 years
to complete.
23
Moreover, a successful out-
come is not guaranteed (as was the case
with oltipraz, an antibilharzial agent
abandoned during clinical trials).
2. A Shift to More Profitable Pro-
duction. To cope with large investments
and reduce duplicate spending, pharma-
ceutical companies started an unprec-
edented cycle of industrial consolidation
and mergers at the end of the 1980s (eg,
Glaxo and Wellcome, Sandoz and Ciba-
Geigy, Roche and Synthex). This consoli-
dation focused on the most profitable seg-
ments of the market (infectious diseases,
cardiovascular conditions, cancer, derma-
tology, and neurology), leaving tropical
medicine largely out of the equation.
3. Competition and Counterfeit-
ing of Drugs. Some drugs patented in
the developed world are being copied in
developing countries, where patent rights
of pharmaceutical products are not pro-
tected. Such production competes, some-
times fiercely, with the innovating labo-
ratory. For example, Bayer Laboratories,
the patent holder of praziquantel, was
outpriced by Shin Poong, a Korean labo-
ratory that had developed a less-
expensive manufacturing process.
24
In
addition to copies of drugs resulting from
a different notion of intellectual prop-
erty rights, there are cases of pure and
simple piracy (appropriation of the name
and appearance of a trademark drug) that
are frequent in countries where infor-
mal markets play a significant role.
25
4. Cost of Adhering to Quality Stan-
dards. There has been a general trend
toward heavier regulations with which
companies must comply to obtain ap-
proval before marketing a drug prod-
uct, which raise the costs of clinical de-
velopment. The necessity of minimizing
therapeutic risks leads to reinforcement
of various quality standards (good clini-
cal, laboratory, and manufacturing
practices).
26
In practice, when clinical de-
velopment incidentally identifies a prom-
ising product (eg, eflornithine for Afri-
can trypanosomiasis) or a new indication
(eg, atovaquone for malaria, ivermectin
for onchocerciasis, and albendazole for
lymphatic filariasis) for the treatment of
tropical diseases, the manufacturer of-
ten decides not to market the drug,
ACCESS TO ESSENTIAL DRUGS IN POOR COUNTRIES
364 JAMA, January 27, 1999—Vol 281, No. 4 ©1999 American Medical Association. All rights reserved.
knowing it would be too expensive. The
company generally decides to either make
exceptional arrangements (eg, dona-
tions in the cases of albendazole, atova-
quone, and ivermectin) or takes nega-
tive action (eg, discontinued production
of eflornithine).
GLOBALIZATION AND DRUGS:
QUESTIONS AND CONCERNS
A discussion of the current landscape in
the area of drug availability would not
be complete without a consideration of
the increasing globalization of the phar-
maceutical industry and the potential im-
plications of recent and upcoming world
trade agreements.
Drugs: Another Industrial Product?
The General Agreement on Tariffs and
Trade (GATT) was signed on April 15,
1994, and was replaced by the WTO
agreement, signed in 1997.
27
This agree-
ment ratifies the worldwide imple-
mentation of a free-trade economy. Its
enforcement with regard to the pharma-
ceutical sector raises certain concerns.
Two types of provision seem particu-
larly important for pharmaceutical com-
panies in developing countries: that
which puts an end to protectionist mea-
sures and that which defines as manda-
tory the protection of patents on drugs
and their respective manufacturing pro-
cesses, such as the Trade Related Aspects
of Intellectual Property Rights Agree-
ment (TRIPS). This is important because
many developing countries do not fully
acknowledge patent protection rights for
pharmaceuticals.
Newly Invigorated Research?
Directors of pharmaceutical companies in
the developed world have stated repeat-
edly that the reason for not conducting
research on tropical diseases is the lack
of protection for innovations in some
developing countries, which would also
explain their limited investments in the
countries concerned.
28
The moment the
enforcement of patent protection becomes
effective (in developing countries, no later
than January 1, 2006) tropical disease
research should logically start again,
funded by Western companies or by
manufacturers in developing countries.
However, it is unlikely that Western
manufacturers will devote much of their
effort to nonsolvent populations, with or
without patents. Manufacturing compa-
nies in developing countries may actu-
ally be motivated to invest more in
research for new drugs, but such invest-
ments will essentially respond to the need
to shift their innovation capacity away
from finding ways to copy the patented
drugs of developed countries and to-
ward discovering new drugs.
29
All things
considered, tropical research may not
have a more promising future, even if pat-
ents are widely enforced.
Table 2. Tropical Disease Drug Development Output, 1975-1997
*
Indication Product
Year Marketed
or Approved Development Context
Marketing Approval of New Chemical Entities for Treatment of Tropical Diseases
Malaria Artemether IM 1997 Chinese academy discovery; public/private collaboration
(WHO-TDR/Rhoˆ ne-Poulenc-Rorer); Rhoˆ ne-Poulenc-Rorer/
Kunmig (China) agreement
Atovaquone/proguanil 1992/1997 Glaxo-Wellcome antimalarial research; initially orphan product
designation and approval for Pneumocystis carinii pneumonia
associated with human immunodeficiency virus
Halofantrine hydrochloride 1992 US Department of Defense discovery (WRAIR); public/private
collaboration (WHO/WRAIR/SmithKline Beecham); US orphan
product designation and approval for acute malaria
Mefloquine 1987 US Department of Defense discovery (WRAIR); public/private
collaboration (WHO/WRAIR/Hoffman LaRoche); US orphan
product designation and approval for acute malaria
Human African
trypanosomiasis
Eflornithine hydrochloride 1990 Hoechst Marion Roussel; US orphan product designation and
approval for human African trypanosomiasis (Trypanosoma
brucei gambiense)
Nifurtimox 1984 Veterinary R&D (Bayer)
Schistosomiasis Oxamniquine 1981 Veterinary R&D (Pfizer)
Praziquantel 1980 Veterinary R&D (Bayer); public/private collaboration (WHO/Bayer)
Helminthic infections Albendazole 1987 Veterinary R&D (SmithKline Beecham)
Benznidazole 1981 Veterinary originally (Roche)
Onchocerciasis Ivermectin 1989 Veterinary R&D (Merck); public/private collaboration (WHO/Merck)
New Indications for Chemical Entities
Human African
trypanosomiasis
Pentamidine isetionate 1950/1984 Rhoˆ ne-Poulenc-Rorer; galenic reformulation (mesylate to
isetionate); US orphan designation and new approval only for
P carinii infection
Leishmaniasis Amphotericin B lipid
complex
1962/1996 NeXstar; galenic reformulation of amphotericin B in liposomes;
US orphan designation and approval only for treatment of
invasive fungal infections
*WHO indicates World Health Organization; TDR, Tropical Disease Research; WRAIR, Walter-Reed Army Institute of Research; and R&D, research and development. Products are
listed by international nonproprietary names.
ACCESS TO ESSENTIAL DRUGS IN POOR COUNTRIES
©1999 American Medical Association. All rights reserved. JAMA, January 27, 1999—Vol 281, No. 4 365
Increasingly Prohibitive Prices?
A study sponsored by US pharmaceuti-
cal companies shows that granting drug
patents does not tend to increase the price
of drugs on the market.
30
This study,
however, does not examine the prices of
new innovative drugs and declares that,
logically, the price of these new drugs
should be higher. Naturally, when the
manufacturing company is assured that
its product cannot be copied, it holds a
stronger position to negotiate prices with
public health authorities. Moreover, the
liberalization of international pharma-
ceutical trade entails the development of
parallel imports between countries where
the same drug is sold at different prices.
Pharmaceutical companies, which are
consequently less inclined to grant sig-
nificantly lower prices to less developed
countries, may instead set unique world-
wide prices or delay marketing their drugs
in developing countries.
28
In either case,
access to drugs is jeopardized.
RECOMMENDATIONS
WHO’s Revised Drug Strategy and the
essential drugs concept are still key strat-
egies to help improve access to essen-
tial drugs and worldwide health. The es-
sential drugs concept is evidence based,
is simple, promotes equity, and is rooted
in firm public health principles. WHO’s
assistance to countries and advocacy
work to promote the essential drugs con-
cept and support countries in the for-
mulation and implementation of na-
tional drug policies has resulted in change
for the better. This strategy is a proven
success but it needs to be continued and
strengthened, and new ways of imple-
mentation have to be explored, given the
changing context. In this spirit, the fol-
lowing recommendations are made with
respect to the 4 main issues that have
been developed in this article.
Procurement of Quality Drugs
To improve the quality of existing drugs
and their procurement, it is important
to develop a permanent “Observatory of
Drug Quality,” established by WHO in
collaboration with organizations in-
volved in the provision of essential drugs
(eg, UNICEF, World Bank, the Euro-
pean Union, and nongovernmental or-
ganizations), that would oversee the
implementation of adequate and effec-
tive control procedures. The practical
knowledge acquired by international or-
ganizations to ensure the quality of ge-
neric drugs must be shared with health
authorities in developing countries. In-
vitations to bid, required by big spon-
sors such as the World Bank, European
Union, and the US Agency for Interna-
tional Development, must combine qual-
ity criteria and lower costs. Further-
more, procurement of drugs should be
centralized at a national level to rein-
force the responsibility of governments
to make procurement, quality control,
stock management, and distribution of
essential drugs a priority.
Increased Availability
To provide better access to effective treat-
ments for people in greatest need, sev-
eral initiatives must be launched now,
even if their results will not be realized
immediately. In the short-term, practi-
cal solutions involving the various part-
ners must be found to maintain the pro-
duction of essential drugs. By establishing
public health priorities, new high-
priced drugs must be made available to
the poor through solutions similar to
those implemented for Expanded Pro-
gramme on Immunization vaccines, for
which the supply is guaranteed by
UNICEF. These drugs could be made
available by creating centralized pur-
chase funds whereby manufacturers
would be guaranteed large sales vol-
umes (financed by existing public and
private funds). The funds would also set
forth, by consensus, compliance with
drug indications. Finally, operational re-
search in the field must be promoted and
developed in close collaboration with
health care professionals in developing
countries. Such research should pro-
duce simple, efficient, and low-cost pro-
tocols without losing sight of the risk-
benefit factor for the poorest countries.
Restart of R&D
In an attempt to offset this costly struc-
tural evolution in the pharmaceutical in-
dustry, several public and private initia-
tives have attempted to introduce public
health criteria in R&D strategies. The
1975 Special Programme for Research
and Training in Tropical Diseases (spon-
sored by the United Nations Develop-
ment Programme, World Bank, and
WHO) has had outstanding results in
strategic research (eg, entomology and
pathogenesis) and has bolstered re-
search potential (eg, epidemiology and
training). However, strategies for prod-
uct R&D that were actually launched in
1994 have yet to produce any convinc-
ing results.
31
Nevertheless, this pro-
gram has succeeded in raising aware-
ness and has promoted reflection on
potentially effective tools, even if most
projects focus exclusively on malaria
(eg, Multilateral Initiative on Malaria).
The US Orphan Drug Act implemented
in 1983 also has produced significant re-
sults for rare diseases (157 new drugs
were commercialized and 837 new in-
dications were developed from 1983 to
1997), but no real impact has been seen
with respect to tropical diseases.
32
We can
therefore conclude that while such ini-
tiatives may occasionally boost the de-
velopment of new drugs (eg, deriva-
tives of artemisinine and pyronaridin),
they are unable to significantly redirect
R&D toward tropical diseases. In the
midterm, a legal and fiscal framework
must be developed to spur R&D on tropi-
cal diseases or related areas, similar to
those developed in the United States for
orphan drugs used in rare diseases.
Humanizing the WTO Agreements
On the whole, it is regretful that WTO
agreements contain no specific provi-
sions that would guarantee both fund-
ing for ambitious tropical pharmaceuti-
cal research and realistic pricing of
potential drugs. However, some devel-
oped countries were able to protect vul-
nerable economic and business sectors
(eg, textiles, agriculture, and culture).
One can understand why wealthy coun-
tries demand that developing countries
comply with regulations on unfair com-
petition. It is obvious that to meet press-
ing public health needs, we need new es-
sential drugs. To develop them, we need
ACCESS TO ESSENTIAL DRUGS IN POOR COUNTRIES
366 JAMA, January 27, 1999—Vol 281, No. 4 ©1999 American Medical Association. All rights reserved.
innovative research and industry. To fund
new research, industry needs commer-
cially viable results. It is therefore vi-
tally important that the pharmaceutical
industry collaborates with organiza-
tions like WHO, UNICEF, and the World
Bank to identify the challenges and get
a clearer view of what they can achieve
together in developing sustainable mar-
kets for new tropical pharmaceuticals.
It must be remembered that those de-
veloping countries that are the main
sources of cheap copies of patented
drugs
31
are nevertheless relatively poor.
Enforcing the WTO regulations will re-
move a source of affordable copies of in-
novative quality drugs on which the poor-
est countries depend. Developing
countries, particularly the less ad-
vanced, should be encouraged to take ad-
vantage of the limited alternatives of-
fered by the WTO agreements.
Specifically, they should be able to ob-
tain compulsory licenses whereby na-
tional authorities allow local manufactur-
ers to circumvent patent rights (with
certain conditions and in return for the
payment of royalties to the inventor, as
stipulated in article 31 of the WTO agree-
ments).
33
Judiciously enforced, such an al-
ternative seems to be the only recourse to
balance the interests of the developing
and developed world.
WHO is in a unique position to argue
the case for health at an international
level. Health-related nongovernmental
and consumer organizations certainly
have a supportive role to play, but WHO
is the only intergovernmental organiza-
tion with a formal international man-
date to protect and advance health in-
ternationally. While WHO’s authority in
this area has suffered in the last de-
cades, part of WHO’s strategy should
now be to clearly and unambiguously put
health first and provide leadership in pro-
moting access to essential drugs.
CONCLUSIONS
Access to essential drugs is a basic
human right often denied to people in
poor countries. However, it would
serve no purpose to demand new pub-
lic health or human rights in a manner
that would suggest that such rights will
soon become a reality. The current situ-
ation points to the opposite. For a great
proportion of the world, health condi-
tions are worsening, and without fun-
damental change in the pharmaceutical
market, perspectives for improvement
are not encouraging.
Acknowledgment: As a medical emergency organiza-
tion present in 80 countries through 400 medical as-
sistance projects, MSF undertakes to speak about the
living conditions of those who cannot speak for them-
selves and to defend their right to vital health care. This
article is mainly based on the field experience of MSF
and our local partners.
We wish to thank the many field volunteers who,
in one way or another, have participated in gather-
ing the information contained in this article. Special
thanks to Nathan Ford for reviewing the manuscript.
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