WHO World Production of Antibiotics
WHO World Production of Antibiotics
WHO World Production of Antibiotics
WHO/EDM/PAR/2004.5
THE WORLD
MEDICINES
SITUATION
i i
CONTENTS
Contributors ................................................................................................ iv
Introduction ................................................................................................. 1
Chapter 1
World medicine production ........................................................................... 3
Chapter 2
Research and development ........................................................................... 11
Chapter 3
Medicines in international trade ..................................................................... 21
Chapter 4
World pharmaceutical sales and consumption ................................................. 31
Chapter 5
Global trends in medicines spending and financing .......................................... 41
Chapter 6
National medicines policies ........................................................................... 53
Chapter 7
Access to essential medicines ........................................................................ 61
Chapter 8
Rational use of medicines ............................................................................. 75
Chapter 9
Medicines regulation .................................................................................... 93
Conclusion ................................................................................................ 109
Statistical annex .......................................................................................... 111
i iiiii
CONTRIBUTORS
The principal writers of this report were Andrew Creese, Nadine Gasman and Mamadou
Mariko. Nadine Gasman produced most of the first draft and began the data collection
and analysis. Mamadou Mariko undertook much of the initial data analysis. The chapter
on expenditure on medicines was written by Patricia Hernandez and Jean-Pierre Poullier,
with data analysis by Chandika Indikadehena. The chapter on rational use of medicines
was written by Kathleen Holloway, Salone Tanna and Richard Laing. Warren Kaplan and
Eshetu Wondemagegnehu contributed the chapter on regulation. Work on the report was
directed by a steering committee comprised of Jonathan Quick, Hans Hogerzeil, Edelisa
Carandang and Jrg Hetzke. Comments on the revised draft, and text contributions were
gratefully received from Guy Carrin, Abayneh Desta, Marthe Everard, Peter Graaff,
Robert Ridley, Budiono Santoso, Bill Savedoff and Kris Weerasuriya. External reviewers
were Catherine Hodgkin, Richard Laing, Libby Levison, Felix Lobo, Helene Mller,
Dennis Ross-Degnan, Sri Suryawati and Anita Wagner. The report was edited and
improved by Sheila Davey. Design and layout were by Renata Kerr. Tables and figures
were coordinated by Lisa Greenough and Liz Murray. Lalit Dwivedi and Kath Hurst
advised on publication and printing. Katy Bozsoki and Lisa Greenough provided secretarial support. Special thanks are due to Pascale Brudon and Nadine Gasman for showing
the way with The World Drug Situation 1988.
i v
iv
WORLD MEDICINE
INTRODUCTION
PRODUCTION
INTRODUCTION
This second review of the world medicines situation (first published in 1988 as The World
Drug Situation) presents the available evidence on global production, research and development, international trade and consumption of pharmaceuticals. In addition, it draws
on the most recent surveys and studies in WHO Member States to examine the state of
national medicines policy. The aim is to provide an easily accessible source of information
on the pharmaceutical situation at global and national levels.
Although the text is based on and around the available data, these data pose several
challenges. For example, reliable data on the large pharmaceutical markets in the worlds
most populous countries, the Peoples Republic of China and India, are in short supply.
Trade, production, expenditure and consumption data all come from different sources.
In addition, the use of monetary values, rather than an indicator of volume, gives a
distorted picture of production and consumption since it fails to reflect the scale of global
consumption of traditional medicines and low-priced generics (both branded and
non-branded).
Another problem is that certain key terms, such as generic medicines, are used differently by different parties, and usage is also changing. While 10 years ago the term drugs
was widely used by WHO and other agencies, in todays usage this seems too vague and
inclusive, and is increasingly understood to refer to illicit substances. As a result, the term
pharmaceuticals is now increasingly used (meaning both medicines and vaccines) or
alternatively medicines. All three terms are used in this report, with explanations given
when needed, and this is reflected in the change in title from the 1988 report.
Meanwhile, the pharmaceutical industry itself is difficult to define. Its products extend
from first aid and cough remedies which are on sale to all, to highly specialized medicines
for use only by hospital specialists. Some definitions bundle veterinary medicines and
vaccines, bulk ingredients, medical devices and diagnostic products with finished pharmaceutical products. The Standard International Trade Classification (SITC Rev 3) distinguishes pharmaceuticals from medicaments and itemizes 57 four- and five-digit sub-items
of these two commodities. Within these classifications the main focus of this report is
medicines for human consumption, including those available only on prescription and
those which can be purchased over the counter. However, in Chapters 1 and 3, the
broader industrial and trade classifications are used.
The manufacturers of pharmaceuticals are numerous and diverse. At one end of the
spectrum are the many firms of all sizes which collect and process herbs and medicinal
plants for use in traditional medicine. No data are available on the volume of products
involved. At the other end of the spectrum are large, integrated transnational corporations, with the capacity to develop new molecular entities and to manufacture, market
and distribute medicines to most parts of the globe. Situated in between is a wide range of
manufacturers differing in size, the kind of pharmaceuticals produced and in manufacturing and marketing techniques. In India, for example, 20 000 pharmaceutical manufacturers have been inventoried, but only 250 of these are in the organized sector, and they
account for 70% of the countrys total output of branded generics. Elsewhere, Chinas
REFERENCE
1 Patents, pills and public health. Can TRIPS deliver? PANOS Report No.46. London, PANOS Institute, 2002.
1
WORLD MEDICINE PRODUCTION
SUMMARY
Trends from 1985 to 1999 indicate that the value of medicine production has
just five countries the USA, Japan, Germany, France and the UK account for
two-thirds of the value of all medicines produced.
Large volume markets of lower-price medicines exist in the highly competitive
and sales of medicines. Ten of these companies now account for almost half of all
sales. This concentration has increased considerably since 1987.
The 10 best-selling drugs account for 12% of the value of all medicine production.
1.1
INTRODUCTION
This chapter summarizes available data on the pattern of global pharmaceutical production.i Production means the value added at each stage of the manufacturing process,
whether it is the manufacturing of active ingredients in bulk from basic chemicals, the
preparation of finished new medical entities, or the repackaging of imported generic
ingredients to make finished branded or unbranded generic products. When measured in
monetary terms, global production is geographically a highly concentrated activity, with
over 90% of world production located in a few high-income countries. The relative
market share of major producing countries has been fairly stable over the past decade.
Two-thirds of the value of medicines produced globally is accounted for by firms with
headquarters in just five countries the USA, Japan, Germany, France and the UK.
Production is also concentrated in a few key products and in a relatively small number of
companies, which often have factories and offices in many countries.
Since monetary values are the most easily available and convenient measures of production, trade and sales of medicines, they are widely used in this report. However, they give
a misleading measure of the therapeutic value of medicines.ii Some of the expensive drugs
As used in the major different industrial and trade classifications the term pharmaceuticals often includes more than
medicines for human use. Vaccines and other biological products, blood and blood derivatives, diagnostic products, and
all of the preceding intended for veterinary use, are frequently bundled together in economic statistics, though finished
pharmaceutical products for human use usually constitute by far the largest single component of this set. While the
concern of this book is with medicines for human use, the industrial production and international trade data in this and
the next chapter should be understood to include these other products.
ii
Therapeutic value can be measured in different ways. Simple measures of clinical improvement, such as fever
reduction or recovery times, are widely used. For comparisons across different conditions and interventions, composite
assessments such as healthy life years gained or disability-adjusted life years gained are increasingly used.
available today have only modest therapeutic benefits, while many inexpensive medicines
are highly effective and safe. Most of the medicines on WHOs Model List are in this
second category. Manufacturers provide a stream of new products for the medicines
market place, usually at higher prices than existing products. New medicines with patent
protection, which may have resulted from costly research and development processes
(R&D), and where large markets are anticipated, tend to be particularly expensive. Yet
price and therapeutic gain are not necessarily related. Large quantities of traditional and
generic medicines are manufactured and consumed, particularly in low-income countries,
and the therapeutic value of these is not reflected in available monetary measures. For
India and China in particular, the dollar value of medicine transactions bears little
relation to the health value of these products. Where available, volume measures such as
weight or the number of prescriptions can change the global perspective on production
and consumption dramatically. However, they still cannot measure the health value of
medicines. India, for example, accounts for about 1% of the worlds production by value,
but 8% by volume (weight). The country ranks thirteenth in world production by value
but ranks fourth in the volume of pharmaceuticals produced.3 However, these measures
are still no closer to an index of therapeutic value, and the available data are too limited to
allow international comparison or analysis of trends.
The total value of global pharmaceutical production in 1999 was just over 320 billion
US dollars.i This corresponded to 1.12% of global gross domestic product (GDP). Table
1.1 shows trends in global production for the period 19851999. The average annual
growth rate of pharmaceutical production over this period was just under 10.5% at current
prices, in comparison with an average annual growth rate of global gross national product
(GNP) of under 7.5%. The value of manufactured pharmaceuticals has thus grown
substantially faster than the total value of goods and services. When these figures are
converted into constant prices to adjust for inflation, the rate at which pharmaceutical
production has outstripped GDP growth increases substantially. The average real growth
rate of GDP was 3.6% per annum and the average real growth rate of pharmaceutical
production was 14.9% per annum.
TABLE 1.1
1985
1990
1999
82,1
175,9
327,2
10,766
22,299
29,232
46,2
140,5
370,1
20,302
24,555
33,672
Source: WHO estimates from database of UNIDO, OECD Health Data, World Development Indicators
1987, 1992, 2001, International Financial Statistics Yearbook, 2002
Note: List of countries from which data were available is given in Annex 1. 1999 values for many
countries are projections, estimated from data from 1981 to the most recent year available.
This estimation corroborates with that of the European Federation of Pharmaceutical Industries and Associations
(EFPIA) which found a value of US$ 350 billion in 2000.
Figure 1.1 shows how total production was distributed among countries according to
their level of economic development, using the World Bank classification of countries,
which groups them according to the level of income as follows:2
High-income:
Middle-income:
Low-income:
Figure 1.1 shows that the high-income countries dominate in world pharmaceutical
production (by value). These countries share of production increased from 89.1% in 1985
to 92.9% in 1999. The combined share of middle- and low-income countries decreased
from 10.9% to 7.1% over the same period.
FIGURE 1.1
90.0
90.5
92.9
80.0
Percentage
70.0
60.0
50.0
40.0
30.0
20.0
10.0
3.9
2.6
2.6
6.9
4.5
Low-income
Middle-income
1985
1990
High-income
1999
1.2
In 2000, nine of the top 100 transnational corporations (ranked by foreign asset value) were pharmaceutical companies.
World Investment Report, 2002, UNCTAD, Geneva.
FIGURE 1.2
Unavailable
Sophisticated industry, significant research
Innovative capability
Active ingredients & finished products
Finished products from imported ingredients
No pharmaceutical industry
(23)
(10)
(17)
(13)
(84)
(42)
groups, reproducer firms manufacture medicines which are not protected by patent
(unless under licence). These firms may be public or privately owned and are typically
small- to medium-sized.
A further 16 countries, including India and China, have innovative capability, meaning
that at least one new molecular entity was discovered and marketed by these countries
in the period 19611990. Over the past decade, important changes have occurred in this
group, which includes some of the worlds biggest exporting countries. India, for example,
has a rapidly growing pharmaceuticals biotechnology market currently estimated to be
worth over US$ 1 billion, and in 19992000 spent some US$ 66 million on medicines
R&D, up from US$ 2.2 million in 197677.1
Elsewhere, 97 countries have a domestic medicines industry based on reproducer firms,
manufacturing branded or commodity generics. While the majority (84) of these manufacture finished products from imported ingredients, 13 countries (including Brazil,
Egypt, Norway, Turkey and Indonesia) are considered to have industries which make
both active ingredients and finished products.
Figure 1.3 shows the share of total pharmaceutical production in each of the five top
producing countries from 1985 to 1999. The combined share of these countries fell from
78% of total pharmaceutical production in 1985 to about 67% in 1999 while both Switzerland and Italy increased their output to about 4.5% each, just behind Germany and the
UK, and just outside the top five. Since 1985, the top 10 medicines producing countries
have accounted for 84%88% of world production. The USA remains the biggest single
producer (by value), accounting for almost one-third of total production, and Japan the
second biggest. Together, these two countries produced 57% of the worlds pharmaceuticals in 1985 and 47% in 1999. The USA lost some of its market share to Japan and
Germany between 1985 and 1990. During the period 1985 to 1999, the market share of the
UK was 6%7%, while that of France remained at 7%8%.
FIGURE 1.3
6%
70%
8%
60%
Percentage
7%
7%
50%
8%
6%
10%
8%
6%
19%
40%
20%
16%
31%
31%
1990
1999
30%
38%
20%
10%
0%
1985
USA
Japan
Germany
France
UK
Figure 1.4 shows pharmaceutical production in constant value terms (to base 1995) in
each of the five major producing countries from 1981 to 1997. Production in the USA
increased in each year throughout the period, while growth in the other four major
producing countries was somewhat less regular.
Pharmaceutical production trends (constant US$ million), top five
countries 19811997
120000
FIGURE 1.4
100000
80000
60000
40000
20000
0
1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997
USA
Japan
Germany
France
UK
The concentration of value in industrialized countries occurs because the parent company
headquarters of major transnational medicines corporations are located there. The parent
enterprises control the assets of parts of the company elsewhere in the world, usually by
equity ownership. The top 10 companies by value of sales accounted for almost half of
estimated world sales for 2001: US$ 175.3 billion out of a total of US$ 364 billion.5 This
figure is consistent with time-series data which show growing concentration in the
share of these top companies, as Table 1.2 shows. Further data on medicines sales and
consumption is presented in Chapter 4.
TABLE 1.2
Number 1 manufacturer
Top 10 manufacturers
1987
1990
1994
1997
2000
3.42
3.99
4.9
4.6
7.3
27.50
28.70
31.8
36.2
45.7
Source: IMS data, cited in J.Morris: Pharmaceuticals Global Insights, February 2002
TABLE 1.3
Total sales
(US$ billion)
Percentage
share in
global sales
Percentage
growth
20002001
Anti-ulcers
19.5
14
18.9
22
Antidepressants
15.9
20
Non-steroidal anti-inflammatory
drugs (NSAIDs)
10.9
16
9.9
Antihypertensive drugs
(Ca antagonists)
Antipsychotics
7.7
30
Oral antidiabetics
7.6
30
7.5
Antibiotics (cephalosporins
and combinations)
6.7
Systematic antihistamines
6.7
22
111.3
34
16
All 10
Source: SCRIP 2747, 17 May 2002, based on IMS World Review data
In value terms, therefore, 10 countries account for 85% of all pharmaceutical production
and 10 companies for about half of all sales. The medicines in the top 10 therapeutic
classes account for one-third of all sales and the 10 best-selling medicines for one-eighth of
the world pharmaceutical market.
REFERENCES
1 Joshi RD. The pharmaceutical industry in India emerging trends. Business Briefing, PharmaTech, 2001.
2 Human development report, 2000. New York, United Nations Development Programme, 2000.
3 Balance R, Pogany J, Forster H. The worlds pharmaceutical industries: an international perspective on innovation,
competition and policy. Report prepared for the United Nations Industrial Development Organization.
Aldershot, UK, Edward Elgar, 1992.
4 Financial Times, 24 July 2002, SCRIP 2747, 17 May 2002.
5 IMS data, cited in SCRIP 2747, 17 May 2002.
10
2
RESEARCH AND DEVELOPMENT
SUMMARY
Governments and pharmaceutical manufacturers are the main funders of the R&D
risks of new product development. However, critics query the actual cost of new
medicines development and point to the neglect of disease problems affecting
poor populations.
The pattern of new medicines R&D reflects market opportunities rather than
global public health priorities. Only 10% of R&D spending is directed to the health
problems that account for 90% of the global disease burden the so-called
10/90 Gap.
Redeployment of a small portion of current public and private R&D funds and/or
private medicines marketing funds could make a major contribution to the development of new medicines for neglected diseases. New incentives are needed for
such a shift to occur.
2.1
INTRODUCTION
Knowledge about the causes and treatment of illness expanded rapidly during the last
century and research into new medicines played an important part in this growth. At the
beginning of the twentieth century, aspirin was the only widely available modern medicine. In the 1940s, the first antibiotic, the first mass-produced antimalarial and the first
antitubercular medicine were introduced. In the 1950s and 1960s, oral contraceptives were
introduced, as well as medicines for diabetes, mental illness, many infectious diseases,
cardiovascular disease and cancer. By the 1970s effective medicines though not always
ideal existed for nearly every major illness we know.i This progress continued throughout the 1980s and 1990s with the development of new drugs against HIV/AIDS.
Since the publication of The World Drug Situation in 1988, the development of medicines
has undergone a major transformation moving from a chemistry-based R&D process
to molecular biology-based processes. Advances in the analysis of DNA have opened up
the possibility of understanding the genetic causes of disease. As a result, many new
Dr Gro Harlem Brundtland. Access to essential medicines as a global necessity: Seminar to mark the 25th Anniversary of
the WHO Model List of Essential Medicines. Geneva, 21 October 2002.
11
This framework helps to put the R&D of new medicines into the wider context of new
medical, or health improving knowledge. While content area number 5 (capacity building) may be seen as an input into the previous four, new knowledge in any of the first four
areas can contribute to improvements in the health of individuals and populations.
Research on the development of new medicines is most likely to fall into category 2 of
this list.
2.2
12
TABLE 2.1
% of total
34.5
47
2.5
30.5*
42
6.0
73.5
100
* A global estimate by PhRMA for 2000 gives a figure of US$ 35.4 billion
Source: Global Forum for Health Research, 2002
The notion of a broad perspective on health R&D is relatively recent and so data are
scarce. Country-specific data are generally limited to OECD member countries, and even
these are not always collected in a consistent way.4 Table 2.2 uses OECD data to estimate
overall spending (public and private) on health R&D in selected countries, and the
proportion of this accounted for by the private sector pharmaceutical industry.
TABLE 2.2
Share of pharmaceutical industry R&D in total health R&D in selected countries, current
US$ billions, 1988 and 1997
Country
USA
Health R&D
1988
Pharmaceutical
industry R&D
1988
Pharm. ind.
as % total
1988
Health R&D
1997
Pharmaceutical
industry R&D
1997
Pharm. ind.
as % total R&D
1997
16.0
5.2
32.6
34.2
15.5
45.3
Japan
7.9
3.2
41.0
12.7
5.3
41.6
France
2.7
0.9
32.9
5.1
2.4
47.2
Germany
1.6
1.3
80.9
2.5
2.1
83.5
Canada
0.5
0.1
21.5
1.1
0.4
34.9
These data show that combined non-industry sources of health R&D remain dominant in
the USA, Japan, France, Germany and Canada. However, in all five countries, industryfunded R&D in medicines has grown faster over the decade than total health R&D, with
the growth in the industry R&D share being particularly fast in the USA, France and
Canada. Figure 2.1 shows longer-term trend data on industry spending on pharmaceuticals R&D, as a percentage of total health R&D, for these countries over the period 1980 to
1999. The gradual increase in the role of private pharmaceutical R&D in total health R&D
in all countries is apparent. Most conspicuous is Germany, where private pharmaceutical
R&D is 72%84% of total health R&D. In the other countries, public and private funding
are more evenly balanced.
13
FIGURE 2.1
Percentage
70
60
50
40
30
20
10
19
80
19
81
19
82
19
83
19
84
19
85
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
France
Germany
Canada
USA
Japan
An OECD study on health R&D broadly confirms the above results and shows much
variety in funding patterns for health R&D in industrialized countries. Different public
and private bodies contribute significantly to total health R&D. However, data sources on
public funding are often fragmented and are seldom organized into the five categories of
health R&D set out above. Figure 2.2 groups the results of in-depth analyses undertaken
in several countries on health R&D and are probably more accurate than the data in
Table 2.2. The figure shows the relative importance of R&D funds from the public sector,
industry and the not-for-profit sector in these countries in 1997.
FIGURE 2.2
11
16
90%
27
80%
Percentage
70%
43
60%
58
15
24
61
64
50%
84
40%
30%
50
20%
42
39
France
Denmark
66
76
Canada
Australia
25
10%
0
USA
UK
Norway
Public
For-profit
Not-for-profit
Among these seven countries, the UKs health R&D spending in 1997 is the most heavily
dominated by private sector pharmaceutical research and Norways the most dominated
14
TABLE 2.3
Health R&D,
US$ million
Czech Republic
Hungary
Poland
Russia
Slovak Republic
Slovenia
Percentage of GDP
for health R&D
84.2
165.5
267.2
188.2
43.0
56.3
0.06
0.16
0.08
0.02
0.08
0.24
Data on health R&D from some developing countries suggest that, as income levels fall,
an even lower proportion of national income is devoted to this type of investment.
Table 2.4 shows that Thailand, the Philippines and Malaysia together spent some
US$ 30 million in 1998 on health R&D. But the proportion of GDP (0.01%0.049%)
allocated for health R&D is generally much lower than in countries in transition, or in
high-income market economies.
TABLE 2.4
Health R&D,
US$ million
Malaysia
Philippines
Thailand
6.9
7.4
15.7
Percentage of GDP
for health R&D
0.01
0.049
0.012
2.3
different technology. Patent protection allows the manufacturer to set prices according to
what the market will bear, which is likely to be well above production cost for breakthrough medicines that are effective in tackling widespread and severe illnesses in highincome markets. The temporary monopolies which patents create are said to be necessary
to reward firms for taking expensive risks in new medicines development. These can be
extremely valuable to companies, as their efforts to prolong patent life beyond the original
period show. However, critics query the actual costs of new medicines development and
point to the neglect of disease problems affecting poor populations.5
The role of medicine patents in an era of increasingly global trade rules is a key issue in
arguments over access to essential medicines, as demonstrated by the conflict over access
to antiretroviral medicines for people with HIV/AIDS in low-income countries. Possible
routes to achieving lower prices for essential medicines in low-income countries are
discussed in Chapter 7. Patent protection is also a contentious issue in high-income
countries, wherever access to effective treatment is impeded by high medicine prices.6
Following several years of rapid innovation from 1980 to the mid-1990s (measured by new
drug approvals in the USA) there is increasing evidence of a recent fall in the output of
global R&D into new medicines.7,8 While R&D spending tripled between 1990 and 2000,
the annual number of new medicines approved fell from its peak of over 50 in 1996 to 32
in 2000, the lowest output for over 20 years. Only one in about 5000 early drug candidates
survive to reach market approval. It is considered likely that over the period to 2006,
major companies will launch an average of 1.3 new active substances each per year. A
forecast published in October 2002 indicated that only four companies were likely to have
more than two new medicine launches in 2003.9 According to an annual review of the
industry in 2000, Pipeline sizes remain static, the number of submissions is decreasing,
and the output of new molecular entities has fallen to a 20-year low.10
After marketing costs, R&D is typically the second biggest item in the spending profile of
large pharmaceutical companies. However, significant differences exist among the major
companies in this respect, as Figure 2.3 illustrates.
FIGURE 2.3
R&D as % sales
R&D spending in US$ billion
15
10
M
ol
ist
Br
r
ye
q
sS
uib
s
ia
ck
he
rti
ac
er
oc
va
M
ra m Value Rin
o
million US$ PPP
N
h
b
P
ec
As
en
raZ
is
on
nt
ns
ve
h
A
% GDP Jo
&
on
ns
h
Jo
Source: Moses Z. The Pharmaceutical Industry Paradox. Reuters Business Insight, 2002
16
K
GS
Pf
ize
Pharmacia (merger with Pfizer completed in April 2003), AstraZeneca, Aventis and Pfizer
all spend at least 15% of their sales revenue on R&D, whereas Merck spends about 5%,
though the actual R&D budgets of these 10 big companies vary less than these percentage
differences.
Many companies involved in the R&D of new medicines, particularly those specializing in
biotechnology, are relatively small and some of these spend far higher proportions of sales
revenue on R&D than the established major companies. Data for 1998 indicate that
several biotechnology firms with sales of between US$ 4 million and US$ 140 million
were spending more on R&D than they were receiving in sales revenue in that year, in one
case 2.4 times more.11 Although annual sales figures are volatile in this sector, such
patterns are clearly not sustainable in the longer run unless companies have significant
non-sales sources of revenue such as research grants or licence revenue. Such data indicate
the levels of both risk and opportunity associated with new medicines discovery.
Figure 2.4 shows R&D spending as a percentage of sales in the five biotechnology companies with the largest research budgets for 2001. In these companies, the size of the R&D
budget in relation to sales more closely resembles that of some major pharmaceutical
companies.
FIGURE 2.4
R&D as % sales
R&D spending in US$ billion
30
20
10
0.31
0.315
0.525
0.344
0.865
Serono
Biogen
Chiron
Genentech
Amgen
% GDP
Source: Moses Z. The Pharmaceutical Industry Paradox. Reuters Business Insight, 2002
2.4
40%
27%
19%
7%
7%
17
The increasing costs of R&D and recent falls in productivity have been factors in encouraging mergers. Much of the analysis of merger prospects is conducted in terms of companies
product pipeline size and complementarity. Rising R&D costs are also prompting manufacturers to develop strategic alliances with small research companies, particularly
biotechnology companies, with partial equity, financing and commitments to buy
products. Over 700 such alliances were consolidated in 1997 and 1998, compared with 319
in 1990 and 428 in 1992.1 Contractual outsourcing of some research and product testing is
also being used. In addition, companies are increasingly trying to implement rational
drug design strategies to guide their R&D efforts.
In terms of product development, the diseases and conditions that affect people in the
worlds major markets largely determine where the pharmaceutical industrys investments go. The Global Forum for Health Research highlights the fact that only 10% of
R&D spending is directed to the health problems that account for 90% of the global
disease burden the so-called 10/90 Gap.3
In 1998, over 60% of total R&D investment was allocated for the development of medicines for the central nervous and sense organs, cancers, endocrine and metabolic diseases
and cardiovascular diseases. Table 2.5 shows that in the period 19811996 there was some
growth in investments in anti-infective and antiparasitic diseases, as indicated by the
number of new compounds. This probably reflects the HIV/AIDS epidemic and the
spread of antimicrobial resistance. However, no new class of antituberculosis medicine
has been developed in almost 20 years despite the high burden of this disease. In 2003
Mdecins Sans Frontires, with the support of several ministries of health and research
institutes, and assistance from some pharmaceutical manufacturers, launched the Drugs
for Neglected Diseases Initiative. Initially focussed on drugs for sleeping sickness, leishmaniasis and Chagas disease, this not-for-profit research organization is specifically
concerned with developing new knowledge in areas with little profit-making potential.12
TABLE 2.5
1981
1986
1996
Anticancer
Neurological
Anti-infective
Musculoskeletal
Diabetic
Cardiovascular
Respiratory
Gynaecological/urological (including sex hormones)
Blood and clotting
Dermatological
Hormones (excluding sex hormones)
Antiparasites
378
582
514
221
250
469
166
104
196
81
124
46
909
967
955
422
480
962
352
173
451
217
204
87
1394
1314
1167
780
777
766
442
438
405
357
154
48
In 1999, 6046 products were in development worldwide and 10 companies accounted for
over 15% of all new pharmaceutical products under development.13 Table 2.6 shows
which companies had most R&D products in development in 1999.
18
TABLE 2.6
However, many of the products under R&D may not be new molecules. Only 40 new
molecular entities were launched in 1999.
Seen in the wider context as part of total health R&D, pharmaceutical companies and
governments are the two major players in the development of new knowledge. Four
decades of rapid advance in the second part of the twentieth century have been followed
by a recent plateau, as the potential of new scientific approaches to aid medicine development slowly unfolds. A small number of national and corporate entities continue to be
the major locomotives in new health and medicine knowledge, though this may change
rapidly in the decades ahead.
The relevance of todays medicine product mix to the worlds health problems could be
greatly improved. Some initiatives are already working to this end. In the vaccines area,
the Global Alliance for Vaccines and Immunization (GAVI) aims to enhance the commercial attractiveness of the market by stimulating demand in developing country markets,
strengthening infrastructure and guaranteeing some purchasing of products. The idea is
that a firm advance commitment to purchase safe and effective vaccines will reduce the
risks faced by private sector manufacturers and help redirect research towards the vaccines
that are a priority for low-income countries.14 The Medicines for Malaria Venture (MMV),
founded in 1999, is a public and private partnership concerned with the discovery,
development and registration of new medicines for the treatment and prevention of
malaria.15 A Global Alliance for TB Drug Development16 was begun in 2000, committed
to delivering a new anti-tuberculosis medicine in a decade. And, as mentioned above, in
2003 the Drugs for Neglected Diseases Initiative17 was launched, driven by public sector
stakeholders, to develop or adapt drugs for patients suffering from important diseases
with little apparent commercial market, such as sleeping sickness and Chagas disease.
These mechanisms fill some important gaps between the opportunities which face
commercial medicine manufacturers on the one hand, and the global burden of disease
on the other.
In the meantime, the medicines market continues to be dominated by lifestyle-related
and convenience medicines for richer populations at the expense of the medicine needs
of the poor. This will not change without more extensive management of the global
medicines market. Redeployment of a small portion of current public and private R&D
funds and/or private medicines marketing funds could make a major contribution to the
development of new medicines for neglected diseases. New incentives are needed for such
a shift to occur.
19
REFERENCES
1 Moses Z. The pharmaceutical industry paradox: a strategic analysis of the countertrends of consolidation
and fragmentation. Reuters Business Insight, Datamonitor, 2002.
2 Dyer G. A risky therapy. Financial Times, 24 July 2002.
3 The 10/90 Report on health research 20012002. Geneva, Global Forum for Health Research, 2002.
4 OECD health data, 2001.
5 Trouiller P et al. Drug development for neglected diseases: a deficient market and a public health policy
failure. Lancet 2002 June 22;359:218894.
6 Mallaby S. Cadillacs for rickshaw riders. Washington Post, 7 October 2002.
7 Pollack A. Drug research yields a decreasing return. New York Times, 19 April 2002.
8 Taylor D. Fewer new drugs from the pharmaceutical industry. British Medical Journal 326 (7386) 408
26 February 2003.
9 Eli Lilly: bloom and blight. The Economist, 26 October 2002.
10 Ogg MS, van den Haak MA, Halliday RG. Pharmaceutical investment and output. CMR International, 2000.
11 SCRIP phamaceutical company league tables, 1991.
12 Mdecins Sans Frontires, Press release 3 July 2003, (http://www.msf.org/countries/).
13 SCRIP yearbook 2000. Vol.1: Industry and companies.
14 State of the worlds vaccines and immunization. Geneva, World Health Organization, 2002.
15 Medicines for Malaria Venture, (http://www.mmv.org).
16 Global Alliance for TB Drug Development, (http://www.tballiance.org).
17 Drugs for Neglected Diseases Initiative, (http://www.accessmed-msf.org/dnd/dndi.asp).
20
3
MEDICINES IN INTERNATIONAL TRADE
SUMMARY
International trade in medicines grew rapidly between 1980 and 1999, from
around US$ 5 billion in 1980 to almost US$ 120 billion in constant price terms.
Trade is dominated by imports and exports among high-income countries.
Industrialized countries are both the biggest individual exporters and the biggest
importers of medicines. The biggest 10 exporting countries accounted for 80%
of world exports, and the biggest 10 importers accounted for over 60% of all
imports in 1999.
This concentration grew between 1980 and 1999, with low- and middle-income
countries losing their combined share of both exports and imports. However,
several individual low-income countries, including India, Pakistan and Indonesia,
expanded their export share during this period. Low-income countries manufacturing
medicines produce predominantly for the home market.
Major exporters among low- and middle-income countries export to other lowand middle-income countries. However Chinas exports are mainly to industrialized
countries. Imports by low- and middle-income countries come mainly from
industrialized countries.
Many countries both import and export medicines. The USA and Japan, the worlds
two biggest producers, were also the biggest net importers in 1999.
WHO recommends that medicines on a countrys essential medicines list should
not be subject to tariffs. However, in the 10 developing countries with the highest
tariffs on imported medicines, the average tariff adds almost 23% to the price of
active ingredients and over 12% to the price of finished medicaments.
3.1
INTRODUCTION
In 1999, international trade in pharmaceuticals represented about 1.8% of global exports
and imports.i Total exports and imports were each worth some US$ 104 billion (Table 3.1).
During the 1990s, trade in pharmaceuticals grew substantially faster than production.
Table 3.1 shows that, in constant price terms, the international trade in pharmaceuticals
has expanded dramatically since 1980, growing three times faster than current prices
indicate.
International trade in pharmaceuticals is dominated by the high-income industrialized
countries. In 1999, they accounted for 93% of global exports and 80% of global imports,
Pharmaceuticals or medicines in this chapter are defined in accordance with Standard International Trade Classification
(Revision3) code 54, which comprises medicinal and pharmaceutical products (541) and medicaments, including
veterinary medicaments (542). This definition includes active ingredients, intermediate products, bulk products and
finished items. Fuller details may be found on the United Nations Statistical Office website at: http://unstats.un.org/
unsd/cr/registry.
21
by value. This concentration in trade has increased since 1980. Between 1980 and 1999,
middle-income countries share of world exports fell, and the shares of both low- and
middle-income countries in world imports dropped significantly.
TABLE 3.1
1980
1990
1999
14.53
5.35
13.54
4.98
36.04
28.79
34.64
27.67
104.22
117.86
104.80
118.53
Source: Commodity Trade Statistics Section, ITSB, United Nation Statistics Division, New York, US
Pharmaceutical Price Index
With the notable exception of Japan, the countries which contribute most to world trade
both in exports and imports are also the worlds major producers: the USA, UK,
Germany and France. Japan, the worlds second largest producer, continues to produce
primarily for the domestic market and since 1980 has reduced its share of the worlds
pharmaceutical imports.
3.2
FIGURE 3.1
92.8
91.8
90.5
92.9
91.5
90
80
Percentage
70
60
50
40
30
20
10
8.3
7.1
1.1
1.1
3.3 3.9
3.6 4.9
2.9 4.2
1980
1985
Low-income
1990
Middle-income
1995
1999
High-income
Source: WHO estimates based on data from Commodity Trade Statistics Section, ITSB, United Nations
Statistics Division, New York
22
Figure 3.2 shows that the value of exports from high-income countries was relatively
stable in the early 1980s, but began to increase steadily from 1986 onwards and rose
steadily throughout the 1990s.
FIGURE 3.2
100
80
60
40
20
19
80
19
81
19
82
19
83
19
84
19
85
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
Low-income
Middle-income
High-income
3.2.1
TABLE 3.2
Germany
Switzerland
USA
United Kingdom
France
Belgium
Italy
Ireland
Sweden
Netherlands
Top countries
World export
1980
1990
1999
Value
% world
Value
% world
Rank
Value
% world
2.272
1.615
2.020
1.732
1.497
0.670
0.688
15.6
11.1
13.9
11.9
10.3
4.6
4.7
5.8612
4.3595
4.1032
4.0404
3.6652
1.6329
1.5169
16.3
12.1
11.4
11.2
10.2
4.5
4.2
0.619
4.3
1.3771
3.8
1
2
3
4
5
6
7
8
9
10
14.978
11.452
11.071
10.053
10.043
6.438
5.607
5.122
4.010
3.852
14.5
11.1
10.7
9.7
9.7
6.2
5.4
4.9
3.9
3.7
11.113
14.526
76.4
100
26.554
36.037
73.7
100
82.626
103.619
79.8
100
Source: WHO estimates based on database from Commodity Trade Statistics Section, ITSB, United
Nations Statistics Division, New York
23
FIGURE 3.3
14000
12000
10000
8000
6000
4000
2000
19
80
19
81
19
82
19
83
19
84
19
85
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
USA
Switzerland
UK
France
Germany
Source: WHO estimates based on database from Commodity Trade Statistics Section, ITSB, United
Nations Statistics Division, New York
Japans situation shows that a big producer is not necessarily a big exporter. Countries
with a manufacturing base differ widely in their propensity to export pharmaceuticals.
Japan exported only 2% of local production in 1985, 3% in 1991 and 4% in 1997.
The low-income manufacturing countries produce predominantly for the local market.
Even in India, with over 20 000 pharmaceutical manufacturers, where the export share
of local production has tripled since 1985, less than 20% of total production enters
international trade.
Major pharmaceutical exports from low- and middle-income countries in 1998 have been
analysed according to their destination, with the results shown in Table 3.3. China is
the only country in this group to export most of its pharmaceuticals to industrialized
countries; all the other exporters supply mainly developing country markets.
TABLE 3.3
China
India
Mexico
Argentina
Korea, Republic of
Brazil
Colombia
Exports to
industrialized
countries
1079
288
304
25
85
64
10
Exports to
developing
countries
592
576
410
277
204
183
173
Exports to
developing countries
as % of total
35.4
66.7
57.4
91.7
70.6
74.1
94.5
Source: Adapted from H. Bale: Consumption and trade in off-patented medicines. Commission on
Macroeconomics and Health, Working Paper WG4:3, May 2001. http://www.cmhealth.org /cmh_papers
&reports.htm#Working Group 4.
24
3.3
80
69.9
70
79.3
78.2
72.4
Percentage
60
50
40
30
22.9
20.1
20
10
7.5
7.2
6.1
17.3
16.7
14.7
5.2
3.4
1980
1985
Low-income
1990
Middle-income
1995
1999
High-income
Source: WHO estimates based on database from Commodity Trade Statistics Section, ITSB, United
Nations Statistics Division, New York
Figure 3.5 shows the value (in current prices) of pharmaceutical imports in each year, confirming the relatively weak growth of middle-income and particularly low-income country imports.
FIGURE 3.5
80000
70000
60000
50000
40000
30000
20000
10000
0
80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99
19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19 19
Low-income
Middle-income
High-income
Source: WHO estimates based on database from Commodity Trade Statistics Section, ITSB, United
Nations Statistics Division, New York
25
Table 3.4 identifies the principal importing countries, which include the five principal
producers. The combined imports of these 11 industrialized countries accounted for 54%
of world imports in 1980 and 66% in 1999. Germany was the worlds leading importer in
1980 and 1990. Japans position as an importer has fallen since 1990.
TABLE 3.4
1980
1990
1999
Value
% world
Value
803.1
1291.0
700.8
516.9
652.6
411.0
654.9
1074.2
568.9
245.2
356.2
5.9
9.5
5.2
3.8
4.8
3.0
4.8
7.9
4.2
1.8
2.6
2540
3396
2646
2064
2817
1193
1510
2836
1447
975.7
860.3
7.3
9.8
7.6
6.0
8.1
3.4
4.4
8.2
4.2
2.8
2.5
11 top
7274.8
pharmaceutical
importing countries
World imports
13543.2
53.5
22286
100
34636
USA
Germany
France
United Kingdom
Italy
Switzerland
Belgium
Japan
Netherlands
Spain
Canada
% world
Rank
Value
% world
1
2
3
4
5
6
7
8
9
10
11
13649
8669.6
7748.7
7746.6
6195.8
5050.5
5023.6
4593.4
4174.6
3509.0
3237.6
13.0
8.3
7.4
7.4
5.9
4.8
4.8
4.4
4.0
3.3
3.1
64.3
69599
66.4
100
104801
100
Source: WHO estimates based on database from Commodity Trade Statistics Section, ITSB, United
Nations Statistics Division, New York
Figure 3.6 shows that, in addition to being the worlds main exporter, Germany was the
most important importer until 1996, when it was overtaken by the USA.
FIGURE 3.6
14000
12000
10000
8000
6000
4000
2000
19
80
19
81
19
82
19
83
19
84
19
85
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
USA
Italy
UK
France
Germany
Source: WHO estimates based on database from Commodity Trade Statistics Section, ITSB, United
Nations Statistics Division, New York
26
Bale (source for Table 3.3) also identifies the leading developing country importers of
pharmaceuticals and the origin of these, summarized in Table 3.5. Pharmaceutical
imports from other low- or middle-income countries account for a minority share in each
of these countries. Import data from the 10 leading African countries (Table 3.6) show
that Uganda and Tanzania were the only two countries which imported more from other
developing countries than from industrialized countries in 1998. A possible explanation
for this is the presence of strong essential medicines policies favouring generic imports in
both countries. However, other factors, such as import prices and the marketing policies
of manufacturers, may also contribute.
TABLE 3.5
Brazil
Mexico
Argentina
Korea, Republic of
China
Colombia
Industrialized
country sources
1325
955
638
463
423
294
Developing
country sources
263
109
139
92
103
202
Imports from
developing countries
as % of total
16.6
10.2
17.9
16.6
19.6
40.7
TABLE 3.6
South Africa
Tunisia
Nigeria
Kenya
Uganda
Senegal
Tanzania
Mauritius
Madagascar
Togo
Industrialized
country sources
Developing
country sources
565
164
79
78
20
49
19
32
13
13
36
8
39
27
34
2
22
6
3
1
Imports from
developing countries
as % total
6.0
4.7
33.1
25.7
63.0
3.9
53.7
15.8
18.8
7.1
3.3.1
27
FIGURE 3.7
Net importers
Net exporters
6.0
5.0
US$ billion
4.0
3.0
2.0
1.0
0.0
-1.0
-2.0
US
A
Jap
an
Ca
na
da
Br
az
il
Sp
ain
Po
la
Au nd
str
ali
a
Sa Turk
ud ey
iA
rab
i
Gr a
ee
ce
Ind
ia
Ch
ina
Be
lgi
De um
nm
ark
Fra
nc
Sw e
ed
en
UK
Ire
la
Ge nd
rm
Sw an
itz y
er
lan
d
-3.0
3.4
28
TABLE 3.7
15%
20%
0%
50%
21.2%
50%
7%
22%
25%
25%
64%
54%
74%
74%
82%
87.5%
14%
18%
20%
15%
0%
s
ri tiu
M au
8.5%
16.25%
25%
al
0%
0%
Nep
Pun
e, In
d
1%
4%
Import tariff
Port charges
Clearance and freight
Pre-shipment inspection
Pharmacy board fee
Importers margins
VAT
Central govt tax
State govt tax
Local town duty
Wholesaler
Retail
vo
Kos
o
0%
en ia
A rm
ia
00
200
0
f ric a
11.7%
il 20
10%
1%
2%
1.2%
2%
Br az
0%
8%
1%
2.75%
th A
Tanz
a
n ia
Ken
y
0%
4%
Sou
200
0
00
a 20
Sri L
an k
a 20
00
4%
5%
1.5%
5%
25%
10%
15%
25%
4%
9%
1.5%
10%
15%
10%
16%
14%
27%
74%
82%
48%
59%
6%
REFERENCES
1 How to develop and implement a national drug policy. 2nd ed. Geneva, World Health Organization, 2001.
2 World health report 2000: health systems measuring performance. Geneva, World Health Organization, 2000.
3 Bale H. Consumption and trade in off-patented medicines. Commission on Macroeconomics and Health,
Working Paper WG4, 2001. Http://www.cmhealth.org/cmh_papers&reports.htm#Working Group 4
4 Levison, L. Policy and programming options for reducing the procurement costs of essential medicines in
developing countries. Http://dcc2.bumc.bu.edu/richard/IH820/Resource_materialsWeb_Resources/
Levison-hiddencosts.pdf
29
30
4
WORLD PHARMACEUTICAL SALES AND
CONSUMPTION
SUMMARY
In 1999, the 15% of the worlds population who live in high-income countries
purchased and consumed about 90% of total medicines, by value. This concentration in the pattern of global sales and consumption has increased over the past 15
years, with the share of the low-income countries falling and that of the highincome countries growing. The market share of the USA alone rose from 18.4% of
the world total in 1976 to over 52% in 2000.
In low-income countries, the share of pharmaceuticals consumed fell from 3.9% of
the total in 1985 to 2.9% in 1999, and their share of sales fell from 0.98% in 1990 to
0.64% in 2000.
The global generic medicines market is worth over US$ 80 billion, about 30% of
total sales, and is much larger than the commonly reported market in unbranded
generics alone.
Patterns of medicines consumption differ between high- and low-income coun-
4.1
31
TABLE 4.1
1985
1990
No.
Value
No.
Low
Middle
High
8
14
22
3,512
5,884
79,006
3.9
6.6
88.9
Total
44
88,402
1001
1999
Value
No.
Value
8
19
20
4,675
13,121
156,578
2.7
7.5
89.8
8
18
22
9,222
18,614
289,822
2.9
5.9
91.2
47
174,374
100
48
317,658
100
Data for high-income countries is again much more complete than for low-income
countries. Although the global picture is incomplete, it is clear that high-income countries
dominate, consuming over 90% of the worlds medicines in 1999. The data suggest that
this dominance has even increased since 1985, with low- and middle-income countries
consumption accounting for a slightly smaller share of the total in 1999 than in 1985.
When population is added to the picture, the pattern of consumption becomes even more
skewed. Figure 4.1 shows the distribution of population by countries level of income in
the same three years.
FIGURE 4.1
50.0
44.9
40.2
40.0
Percentage
49.5
32.4
33.5
30.0
17.8
20.0
17.1
14.9
10.0
0.0
Low-income
Middle-income
1985
1990
High-income
1999
Source: WHO estimates based on statistics of the UNDP Human Development Report (2001)
In 1985, the 18% of the world population living in the high-income countries consumed
89% of the worlds pharmaceuticals: by 1999, the population share of these countries had
fallen to 15% but their pharmaceutical consumption had grown to 91% of the total.
32
4.2
TABLE 4.2
Value
Low (n=4)
Middle (n=23)
High (n=25)
Total (n=52)
1990
US $ billion
Value
2000
US $ billion
1.25
13.21
113.28
1.0
10.3
88.7
1.81
29.38
251.30
0.6
10.4
89.0
127.74
100
282.49
100
Non-prescription medicines, of which the great majority are over-the-counter sales for
self-medication, accounted for an additional US$ 33.9 billion of sales in 2000. Adding
together the prescription and non-prescription sales gives a global medicines total of just
over US$ 316 billion in 2000, which compares reasonably with the calculated 1999
consumption total of US$ 317.6 billion in Table 4.1.
Available data on global medicine sales show a similar pattern of skewness towards highincome countries as do production and consumption data. In 1999, 15% of the worlds
population lived in high-income countries, 49% in middle-income and 36% in lowincome countries. Once again, the disparity between sales and population is dramatic: at
the top end, approximately 15% of the worlds population bought almost 90% of the
worlds medicines; at the bottom end, over one-third of the worlds population bought
less than 1% of the worlds pharmaceuticals. For the half of the worlds population who
live in middle-income countries, their share in total sales accounted for a little over 10%
in 2000. Table 4.3 shows a remarkable concentrating trend in the global shares of both
individual countries, such as the USA and Japan, and of the top 10 markets as a group,
which accounted for 62.4% of global sales in 1976 and 98.7% in 2000. Table 4.3 also shows
strong concentration even within the high-income countries. In 2000, over 95% of global
sales were concentrated in the top 10 pharmaceutical markets: USA, Japan, France,
Germany, UK, Italy, Spain, Canada, Brazil and Mexico. In India, which was in the top 10
in 1985 but not in 2000, sales were estimated to be US$ 3.4 billion in 2000.
33
TABLE 4.3
1976
Value % world
Country
1985
Value % world
Country
2000
Value % world
USA
Japan
Germany
France
China
Italy
Spain
Brazil
UK
Mexico
7.90
4.02
3.41
2.70
2.60
1.90
1.32
1.21
1.03
0.77
18.4
9.3
7.9
6.3
6.0
4.4
3.1
2.8
2.4
1.8
USA
Japan
Germany
China
France
Italy
UK
India
Canada
Brazil
26.45
14.04
6.00
4.70
4.47
3.67
2.35
1.78
1.69
1.41
28.1
14.9
6.4
5.0
4.8
3.9
2.5
1.9
1.8
1.5
USA
Japan
France
Germany
UK
Italy
Spain
Canada
Brazil
Mexico
149.5
51.5
16.7
16.2
11.1
10.9
7.1
6.2
5.2
4.9
52.9
18.2
5.9
5.7
3.9
3.9
2.5
2.2
1.8
1.7
26.86
43.05
62.4
100
Top 10
World sales
66.56
94.10
70.8
100
Top 10
World sales
279.3
282.5
98.7
100
Top 10
World sales
Source: World Drug Situation 1988 and IMS Health, IMS MIDAS Customized Insights (October 2001)
The information contained in this study is a guide to sales and not a guide to consumption.
4.3
After expiry
of patent...
Generic versions
of originator
becomes a multisource drug
Unbranded
commodity
generics
Before expiry
of patent
Copy versions
legality depends on
patent jurisdiction
Branded
generics
34
process from the original brand. At the other end of the spectrum are some generic
pharmaceuticals known as commodity generics. Generics in general are pharmaceutical
products usually intended to be interchangeable with the originator product, marketed
after the expiry of patent or other exclusivity rights and usually manufactured without a
licence from the innovator company. This large category includes pharmaceuticals that
were formerly patent protected, but whose patent has expired. It also includes pharmaceuticals that have never been patented, as well as copies of patented pharmaceuticals in
countries without such a patent. Whether such copies are legal or illegal depends on the
patent jurisdiction in which such pharmaceuticals are manufactured.
A valuable sub-sector of the generics market is generic medicines with their own brand
names, each manufactured by a single company and hereafter referred to as other
brands. Yet other generic medicines (commodity generics) are sold under the generic
name and may be manufactured and marketed by many companies. This is a highly pricecompetitive sub-market, as buyers can choose among several sources of supply of chemically identical medicines. Many developing countries also have important markets in
counterfeit medicines. A counterfeit medicine is defined as one which is deliberately and
fraudulently mislabelled with respect to identity and/or source. Counterfeiting can apply
to both branded and generic products and counterfeit products may include products with
the correct ingredients, wrong ingredients, without active ingredients, with incorrect
quantity of active ingredient or with fake packaging.1 Though no precise figures exist on
the scale of the counterfeit problem, it affects countries at all income levels and appears to
be most widespread where the manufacture, importation, distribution, supply and sale of
medicines are less effectively regulated and where enforcement is weak.
On the manufacturing side, the distinction between research-based (i.e. originator)
companies and generic manufacturers is frequently blurred. Novartis and Merck, for
example, both major innovator companies, have generics subsidiaries which account for
important shares of the worlds generics.
Recent changes in international trade law to strengthen the protection of intellectual
property (patent) rights2 have coincided with national policy changes in many countries
to promote opportunities for competitive pricing of generic medicines. By 2005, patent
rights on new medicines must be respected in all World Trade Organization member
countries except those classified as least developed, which have the possibility to
negotiate extensions.
The complexity of the definition of generic medicines has led to considerable understatement of their importance in the global market. A recent study puts the size of the global
generics market at about US$ 20 billion. However, like several other studies, it restricts
the definition of generic to unbranded (commodity) medicines (SCRIP Global Generic
Pharmaceuticals 2002). Using IMSs definition of other brands (branded generics and
other copy drugs, both legal and pirated) in addition to unbranded generics considerably expands this market to some US$ 87 billion in 2000, about 30% by value of total
world sales. Figure 4.3 shows generic market shares for 52 high-, middle- and low-income
markets for which comparable data are available for 1990 and 2000.
Comparing sales data for 2000 across country income groups clearly shows a larger share
of originator/licensed medicines in the total sales of high-income countries about twothirds in the latter compared with less than one-third in low-income countries and
around 40% in the middle-income group. Comparing 1990 with 2000 sales, the data also
show that the share of other brand generic medicines in total sales grew in low-income
35
markets but fell in middle- and high-income markets. Over the same period, the share of
commodity generics in high-income markets grew slightly.
FIGURE 4.3
Percentage
70
60
50
40
30
20
10
0
Low 1990
Low 2000
Commodity generics
High 1990
High 2000
Status n/a
In countries at all income levels, the period saw a growth in clarity regarding the legal
status of medicines, probably a reflection of the strengthening of intellectual property
rights referred to above. The share of the market for which patent status information was
not available fell from 18% to 13% in low-income markets, from 14% to 10% in middleincome countries, and from 10% to 6% in high-income markets.
Comprehensive and reliable data for the decade from 1990 are unfortunately not available
for some major markets, such as Russia, China and India. The rate of growth of originator and licensed medicines in some of the countries in transition to mixed economies has
been far greater than the averages in Figure 4.3. In the Czech Republic, for example,
originator brand and licensed medicines grew from 15.5% of the total market to nearly
45% from 1990 to 2000. Hungary, the Slovak Republic and the Republic of Korea also
experienced faster than average growth in this category of medicines. In contrast,
Pakistans market showed the largest recorded shift away from originator and licensed
medicines, and towards other brands over the decade.
Table 4.4 indicates that in 1997 the leading seven generic markets (unbranded plus
branded) were all in high-income countries. The biggest of these, in absolute value, are
the USA, Japan and Germany. Yet these major generics markets are in countries with very
different health financing arrangements. In the USA, the incentive to keep medicine costs
to patients at a low level derives from two pressures: a large population (64.5 million
people, almost a quarter of the total population) who lack any insurance cover for medicine costs3, plus increasingly cost-conscious insurers and providers for the insured majority. In Germany and Japan, by contrast, where most people have been covered by social
insurance for a long time, pressure for cost-containment has come from insurers and
government.
36
TABLE 4.4
Value of generic
market, US$ billion,
20001
Generic share
as % of total
market (value)2
Generic share as %
of total prescriptions
volume (year)2
31.7
5.7
11.0 (1997)
17.0 (1997)
France
UK
4.4
4.5
2.0
21.7 (1997)
44.6 (1998)3
40 (1988)
www.inpharm.com4
3.0 (1996)5
47 (1998)
www.inpharm.com4
Italy
Brazil
Spain
Argentina
Mexico
Canada
3.0
2.4
2.2
2.0
2.0
1.9
27.9
47.5
31.2
58.6
40.0
15.0 (1997)
USA
Germany
40 (1997)
Sources:
1
IMS customized study (value and generic share in total value)
2
de Joncheere et al, Drugs and money. Amsterdam, IOS Press, 2003
3
Scott-Levin. Source prescription audit (SPA), December 1999
4
Reuters Business Insights
5
SCRIP complete guide to the world generic drugs market, 1999
TABLE 4.5
For unbranded generics, the USA and the UK represent the major markets where generics
are traded at very low prices as commodity items. In this relatively underdeveloped
market, sales efforts are generally focused on pharmacists. In the branded generics
markets, by contrast, marketing is oriented towards doctors to promote branded generics
such as branded products, even if the emphasis is still on lower prices. IMS data for the
USA gave the average price of an (unbranded) generic prescription medicine as US$ 14.70
in 2002, in contrast to the price of brand name drugs (both patent and branded generics)
of US$ 77.02.4
Growth in the generics market is encouraged by the needs of governments and insurers to
contain spending, and also by the time-limited nature of intellectual property protection.
Public policy to encourage such prescribing and dispensing in the UK, for example, led to
the level of generic prescriptions written increasing from 43% in 1992 to about 50% in 1996.
The expiry of patents also creates opportunities for more competition in the manufacture
of commercially successful medicines. Table 4.6 shows expected patent expiry dates for
37
16 products, together worth US$ 27 billion in sales (1999) and due to become off-patent
before 2005.
TABLE 4.6
Manufacturer
Clarithromycin
Lisinopril
Omeprazole
Ciprofloxacin
Pravastatin
Cefuroxime axetil
Nabumetone
Ondansetron
Fluoxetine
Nizatidine
Lisinopril
Lovastatin
Simvastatin
Azithromycin
Fluconazole
Loratidine
Abbott
AstraZeneca
AstraZeneca
Bayer
Bristol-Myers Squibb
GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline
Eli Lilly
Eli Lilly
Merck
Merck
Merck
Pfizer
Pfizer
Schering-Plough
Patent expiry
2002
2001
2001
2003/4
2005
2000/3
2002
2005
2001/3
2002
2001
2001
2005
2002/5
2004
2002/4
1.25
1.22
5.91
1.69
1.8
0.42
0.45
0.42
2.61
0.35
0.81
0.6
4.49
1.3
1.0
2.7
4.4
38
TABLE 4.7
Country
USA
UK /USA
USA
Sweden/UK
France/Germany
USA
USA
Switzerland
USA
USA
USA
Switzerland
Germany
USA
USA
Japan
Rank
1977
8
1413
11
6
10
5
3
15
Rank
1985
Rank
1998
Rank
2001
6
12
1
10
13
2
9
15
5
5
12
1
4
2
6
9
7
11
8
10
3
14
13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Table 4.8 shows that in 1997 the Swiss company Novartis had captured the largest share
of the worlds generic drugs market, by value of sales. A year later, Novartis was ranked
the seventh leading pharmaceutical company in the world on the basis of the total value
of the companys sales of both branded and generic medicines. Table 4.8 also reveals that
American companies largely predominate among the worlds leading generic medicines
producers. In 1997, almost half of the top 15 generic medicine manufacturers were from
the USA, the biggest generic market.
TABLE 4.8
Company
Country
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Novartis
Teva
ICN
Merck
Ivax (IVX Bioscience)
Mylan
Apotex
Schein
Ranbaxy
Ratiopharm
Hexal
Novopharm
Barr
Alpharma
Watson
Switzerland
Israel
USA
USA
USA
USA
Canada
Germany
India
Germany
Germany
Denmark
USA
USA
USA
Note: * year ending 31 March 1998; **estimated; *** year ending 30 June 1998
Source: Hay and Atkinson: SCRIPs complete guide to the world generic drugs market, volume 2, 1999
39
Table 4.9 identifies the worlds major biotechnology companies in 2001, a league table
which has changed even more rapidly than that of pharmaceutical manufacturers.
TABLE 4.9
Amgen
Genentech
Serono
Genzyme
Chiron
Biogen
Immunex
MedImmune
Celltech
IDEC
4015
2202
1376
1224
1141
1043
987
619
437
273
REFERENCES
1 Counterfeit drugs: report of a joint WHO/IFPMA workshop. Geneva, World Health Organization, 1992
(unpublished document WHO/DMP/CFD/92).
2 Globalization, TRIPS and access to pharmaceuticals. WHO Policy Perspectives on Medicines No.3. Geneva,
World Health Organization, 2001.
3 Kreling DH et al. Prescription drug trends: a chartbook. Menlo Park, Calif., Kaiser Family Foundation, 2002.
4 As drug patents end, costs for generic drugs surge. New York Times, 27 December 2002.
40
5
GLOBAL TRENDS IN PHARMACEUTICAL
SPENDING AND FINANCING
SUMMARY
In a quarter of WHOs 192 Member States medicines spending was less than
was almost 100 times more than in low-income countries nearly US$ 400
compared with slightly over US$ 4. At opposite ends of the spectrum, there is a
thousandfold difference between what the highest spending and lowest spending
countries spend on pharmaceuticals per capita.
Private spending by households is today the principal source of pharmaceutical
of countries, most countries with high HIV/AIDS mortality are still spending less
than US$ 5 per capita on medicines overall.
A much greater role for public finance of medicines is needed to counterbalance
5.1
NHA provide a quantitative, systematic, consistent and comprehensive model of resource flows in health systems.
41
TABLE 5.1
Measured
expenditure level
Share of
world total
1990
2000
1990
2000
Share of
expenditure
on health
%
1990
2000
245,000
196,019
41,916
6,568
440,300
345,758
82,740
10,675
100
80.2
17.1
2.7
100
78.7
18.8
2.4
14.2
13.0
22.5
20.8
15.2
13.8
24.8
19.2
The data on total pharmaceutical spending in Table 5.1 indicates that, at 15.2% of total
expenditure on health in 2000, pharmaceuticals account for an important share of all
health resources. According to the WHO World Health Report 2003, expenditure on medical
goods and services constituted 8.1% of the combined GDP for the WHO Member States in
42
5.2
This figure compares with the figure of 1.12% in Chapter 1, estimated by different procedures, for 1999. The ratios cited
in the WHR 2003 are measured in international dollars, a numeraire that emulates economy-wide or GDP purchasing
power parity values. At conventional average exchange rate, the health spending to GDP and the pharmaceutical
spending to GDP ratios are 9.2% and 1.4% respectively. This report uses mainly exchange rate values, which are more
relevant than international dollars to analyse pharmaceutical expenditure trends as these are widely traded at their actual
exchange rate value. However, international dollars are more relevant to compare GDP and real health spending.
ii
These averages mask large differences within each grouping, including within the OECD group, in which the United
States experienced an above trend expansion of its pharmaceutical consumption offset by restraint in several other
countries of that group.
iii
This chapter relies on what countries disclose and on data collated from hundreds of official statistical sources, as well
as private analyses of the health systems of the world and pharmaceutical usage. That measurement will evolve as
more sources become accessible and greater comparability is possible. As of mid-2004, the data used are the most
comprehensive set constructed.
43
FIGURE 5.1
Value in US $
400
300
200
100
0
1993
1994
1995
1996
High-income
1997
1998
1999
Middle-income
2000
2001
Low-income
Figure 5.2 shows trends in a selection of large countries from 1990 to 2001, measured at
exchange rates.
FIGURE 5.2
600
500
400
300
200
100
0
1990 1991
1992
Brazil
Japan
44
1993
1997
France
South Africa
India
TABLE 5.2
Measured
minimum
1990
2000
Measured
maximum
1990
2000
Average
expenditure
1990
2000
< 0.5
50
2
< 0.5
330
330
79
19
49
240
18
3.6
0.6
84
4
0.6
549
549
198
26
74
396
31
4.4
5.3
Straight proportions in the strict sense are not applicable. In the wealthier countries, the range is from 9.2% to 35% of
health expenditure whereas in the poorer countries it is from 5% to 70%. In dollar terms, in the countries with higher
per capita expenditure on pharmaceuticals, the range is from US$ 84 to US$ 549 (as indicated in Table 5.3), while in the
poorer countries it is from less than US$ 0.6 to US$ 26.
45
FIGURE 5.3
Government
Private
350
300
250
200
150
100
50
0
90
ld
or
W
00
ld
or
W
w
Lo
90
w
Lo
00
M
90
le
d
id
00
le
d
id
90
gh
i
H
00
gh
i
H
TABLE 5.3
1990
Private
Public
57.8
54.2
72.6
71.4
42.2
45.8
27.4
28.6
2000
Private
Public
60.6
57.8
70.9
71.6
39.4
42.2
29.1
28.4
46
For countries in all income clusters, the governments share in total pharmaceutical
spending (Table 5.4) has fallen from 42.9% to 39.2%.
TABLE 5.4
Private
1990
Govt.
Total
Private
2000
Govt.
Total
28
130
13
2.6
21
110
5
1
49
240
18
3.6
45
229
22
3.2
29
167
8
1.1
74
396
30
4.4
In part, this may have occurred because, unlike catastrophic costs for an episode of
inpatient care, medicine costs are a long string of smaller, recurrent bills. This makes them
a more avoidable expense for insurers, including public insurers. Another reason may be
that pharmaceutical access through pharmacies involves a wider range of both medicines
and retail suppliers than through hospital-based (particularly surgical) activity. As a result,
it is a less manageable object for public subsidy and regulation than hospital-based care
where it is easier for governments to control spending. However, increased private
funding of a wider range of pharmaceutical products does not necessarily equate with
access to better medical care.
Behavioural patterns also have a key bearing on the consumption of medicines. Although
pharmacies are scarce in most rural areas and in some suburban areas, they are the main
source of non-prescription medicines for most people, provided the shelves are wellstocked. As a result, a great deal of self-diagnosis, self-medication and re-use of prescriptions occurs often reinforced by pharmacists on the basis of very poor information
about the properties of the medicines they sell.i
As Table 5.3 shows, in each of the income clusters, households account for the majority of
pharmaceutical spending. However, the impact of this varies greatly. While in the highincome countries, a prominent concern is lengthy waiting lists for elective surgery, the
poor in low-income countries are more likely to be preoccupied with how many items on
a prescription they can afford to buy with the little money they have.
During the 1990s, public finance constraints prevented most low-income countries from
substantively improving their pharmaceutical benefits. Although some middle-income
countries have succeeded in making modest improvements in health insurance cover,
household disbursements for health overall have increased in nominal terms by 30%
against a 2.8% increase in real income per head during that period.ii
i
While pharmaceutical retailing is a quasi public service involving medical advice, it is also a retail trade in which a
retailer addresses an uninformed client, often on the basis of poor knowledge about the objectives of medicines or their
appropriate use. In therapeutic as well as in economic terms, the shift towards a greater reliance on private finance
cannot necessarily be equated as some textbooks may suggest with improved allocation of resources, greater
efficiency, greater effectiveness, greater empowerment of the stakeholders. When the functions of prescribing and
dispensing are combined, as with dispensing doctors or prescribing pharmacists, overprescribing is likely.
ii
Measured in purchasing power parity/international dollars GDP per capita has increased substantially more than in
figures at exchange rate US dollars: an estimated 22%.
47
5.4
TABLE 5.5
Medicines share
in government
spending
on health (%)
Medicines share
in total
government
spending (%)
Per capita
expenditure
at average
exchange rate (US$)
1990
2000
1990
2000
1990
2000
10.2
9.9
11.9
21.5
10.2
9.8
13.1
16
3.0
2.8
4.5
3.5
3.9
3.6
5.6
3.6
21
110
5
1
29
396
8
1.1
The recent reduction in public commitment towards medicines in total health financing
reflects a public finance constraint not limited to health, but shared by all public programmes. In the low- and middle-income countries, the share of medicines in total
government spending has been inching slightly upwards (Table 5.5), from 3.5% to 3.6%
and from 4.5% to 5.6% respectively. However, in low-income countries government
spending priorities in the health system have clearly emphasized other inputs, as the share
of medicines in government health spending fell dramatically from 21.5% to 16%. This
downturn has occurred in countries which have been more severely affected by heavy debt
burden and/or major epidemics of diseases such as HIV/AIDS. Figures 5.4 and 5.5 show
pharmaceutical spending trends in GDP.
48
FIGURE 5.4
Percentage of GDP
2.5
2.0
1.5
1.0
0.5
0
1990 1991
1992
1993
Bahamas
China
Nepal
1997
Cape Verde
Maldives
Tonga
Chile
Mongolia
FIGURE 5.5
Percentage of GDP
2.0
1.5
1.0
0.5
0
1990 1991
1992
Australia
Finland
Luxembourg
Spain
1993
1997
Czech Rep.
Iceland
Norway
UK
Denmark
Korea, Rep. of
Poland
USA
5.5
49
grants for the supply of vaccines and some essential drugs, as well as for other targeted
programmes.
However, important though it is, the impact of health funding by external agencies
should not be overstated. Greater international solidarity has certainly helped to increase
the supply of pharmaceuticals in some of the poorest countries. In Mozambique, for
instance, in 1987 only 10.1% of recurrent expenditure on pharmaceuticals came out of
budgetary sources and 89.9% out of external funding; in 2000, these ratios were correspondingly 18.9% and 81.1%.i Yet, in average per capita expenditure terms, the total
outlay on pharmaceuticals in both years was only US$ 1 per head.
In only seven heavily aid-dependent countries (i.e. in which the share of external resources in total expenditure on health is over 20% of the resources available to the government) has external assistance raised per capita expenditure on pharmaceuticals above
US$ 5 dollars per head: Belize, Djibouti, Equatorial Guinea, Kenya, Kyrgyzstan, Papua
New Guinea and Zimbabwe.ii
TABLE 5.6
South Africa
India
Kenya
Zimbabwe
Nigeria
Ethiopia
United Republic of Tanzania
China
Zambia
Democratic Rep. of Congo
Malawi
Cte dIvoire
Cameroon
Mozambique
Thailand
Uganda
Rwanda
Burkina Faso
Sudan
Burundi
Ghana
Haiti
Guinea
Total
Estimated
treatment need
2003
(US$ thousands)
Percent
of global
treatment need
934
616
378
366
362
299
242
207
196
191
136
127
124
123
107
97
78
71
62
60
58
56
56
15.8
10.4
6.4
6.2
6.1
5.0
4.1
3.5
3.3
3.2
2.3
2.1
2.1
2.1
1.8
1.6
1.3
1.2
1.1
1.0
1.0
1.0
1.0
4946
83.6
50
A great deal of attention has been given to recent price arrangements that dramatically
lower the cost of HIV/AIDS treatment in low-income countries. The costs of treatment
for HIV/AIDS and accompanying opportunistic infections nevertheless remain relatively
expensive, in excess of US$ 300 per annum in 2003. Yet, in only eight of the 23 countries
which make up 80% of the global treatment need, was the average measured spending on
pharmaceuticals above US$ 5 per head in 2000 (Table 5.6).
Pharmaceutical financing reveals the same patterns of gross imbalance observed in other
aspects of the global medicines market place. Falling public support by governments for
medicines has pushed the financial burden on to households in both high- and lowincome countries, with attendant risks to public health objectives. While external support
made a difference in some settings, adequate and sustainable financing of medicines
remains a remote prospect for almost half of the worlds population.
As experience with responses to the HIV/AIDS epidemic shows, the programmes developed to supply medicines at discounted prices have so far made little more than a dent in
the accessibility problems faced by people in the low-income countries. A much greater
role for public finance is needed to counterbalance the consequences of market income
distribution. Both developing country governments and external funding agencies have
roles to play.
51
52
6
NATIONAL MEDICINES POLICIES
SUMMARY
Medicines are important both to a countrys economy and to the health of its
stakeholders know their roles, rights and obligations in relation to medicines, and
that these are supported by monitoring and effective regulation.
Putting policy into practice entails a three-part process: formulation, implementa-
number of countries with a national policy on medicines increased from only five
in 1985 to 108 in 1999.
Progress in this period in developing national medicines policies was most rapid in
low-income countries (up from 4 to 54) and in middle-income countries (up from
1 to 43).
However, almost two-thirds of the countries with a medicines policy document
shortages.
6.1
INTRODUCTION
Pharmaceutical markets are both complex and important and require careful stewardship.
Medicines are important both to a countrys economy and to the health of its people, but
these two interests can conflict. National laws and regulations relating to medicine are
often inconsistent and incomplete and, without an integrated framework, can frustrate
the objectives of overall health policy. A clear medicines policy supported by credible
institutions can ensure that all stakeholders know their roles, rights and obligations
in relation to medicines, and that these are supported by monitoring and effective
regulation.
WHOs guidance on national medicines policy is fully set out in a publication that
outlines the policy process and the necessary supporting legislation, and identifies the
principal components of a national policy.1 A medicines policy document is important as
it reflects formally the decisions, aims and commitments of government and others. A
national policy on medicines outlines a countrys goals and provides a framework for
achieving them, setting out the roles and responsibilities of the main actors in both public
and private sectors. Since 1990, many countries have shown their willingness to improve
53
Box 6.1 summarizes the main stages in the process of medicines policy formulation.
BOX 6.1
6.2
TABLE 6.1
Number
of countries
Percentage
of countries (%)
67
44.1
3.3
36
44
23.7
28.9
152
100.0
Figure 6.1 shows the geographical distribution of countries with a national medicines
policy.
54
FIGURE 6.1
1
2
3
4
5
6.3
=
=
=
=
=
(67)
(5)
(36)
(44)
(40)
TABLE 6.2
Formulation of national medicines policies in low-, middle- and highincome countries in 1999
Status of national
medicines policy
document
Low-income
Middle-income
High-income
Total
Number
%
of countries
Number
%
of countries
Number
%
of countries
No.
Official document
within 10 years
Official document
> 10 years
Draft document
No document
35
56
29
41
17
67
18
6
29
9
17
24
24
34
1
14
6
77
36
44
Total
63
100
71
100
18
100
152
Table 6.2 shows a substantial correlation between the existence of national medicines
policies and a countrys level of income. The lower the level of a countrys income the
greater the percentage of countries with a national medicines policy document. Among
55
low-income countries, 90% of responding countries had official national medicines policy
documents in 1999 compared with 66% for middle-income countries and only 22% for
high-income countries.
WHO guidelines on national medicines policies were first published in 1988. Figure 6.2
shows trends in the formulation of national policies from 1985 to 1999, by income level.
It reveals that in the low-income group of countries, the number of countries with a
national medicines policy grew from four in 1985 to seven in 1990, 29 in 1995 and 57 in
1999. In the middle-income group, the number went up from one in 1985 to three in
1990, 16 in 1995 and 47 in 1999.
In high-income countries, the formulation of national medicines policies began more
recently, particularly in Europe, where only two countries reported having such policies in
1995 and four countries in 1999. However, many high-income countries have extensive
laws, regulations and institutions corresponding to much of the implementation machinery of a national policy, without having the overall framework in the form of a written
policy. For example, in the 1990s, the government of Australia began implementing
several components of a national medicines policy, such as the development of a pharmaceutical benefits system to promote equitable and widespread access to care, the development and promotion of treatment guidelines and prescriber training. Steps were also
taken to ensure the viability of a competitive national pharmaceutical industry. Only in
2000, these actions were integrated and amplified to form a national medicines policy,
thus making Australia one of the pioneer high-income countries to implement a
comprehensive approach to medicines.
FIGURE 6.2
Percentage
40
30
20
10
0
1985
1990
Low-income
1995
Middle-income
1999
High-income
6.4
56
However, in some countries, national medicines policies are implemented without such a
plan.
Figure 6.3 shows the status of implementation plans for national medicines policies in
countries with a policy document. It shows that:
In 1999, almost two-thirds of the 108 countries with a national medicines policy
document (official or draft) had not yet established a plan to implement their national
medicines policy.
Almost one-quarter of the countries with a national medicines policy document had
established a plan of the action within five years of formulating the policy, and 2% took
longer than five years to establish their implementation plan.
Only 10% of countries with a draft policy document also had a plan to implement the
policy.
FIGURE 6.3
Number of countries
70
69
60
50
40
30
26
20
11
10
2
0
Existence of
NMP document,
but no
implementation
Implementation
plan with draft
NMP document
Implementation
plan within 5 years
with official NMP
document
Implementation
plan > 5 years
with official NMP
document
Figure 6.4 shows the geographical distribution of countries with implementation plans.
An additional four countries had implementation without a framework national medicines policy: two low-income countries (Cte dIvoire, Rwanda) and two middle-income
countries (Libyan Arab Jamahiriya, Tunisia).
57
FIGURE 6.4
6.5
(27)
(2)
(11)
(5)
(69)
(78)
58
Low-income
Middle-income
High-income
Number
%
of countries
Number
%
of countries
Number
%
of countries
13
23
12
26
25
3.5
10
11
3.5
34
60
28
59
75
57
100
47
100
100
REFERENCES
1 How to develop and implement a national drug policy. 2nd ed. Geneva, World Health Organization,
2001.
2 How to develop and implement a national drug policy. WHO Policy Perspectives on Medicines No.6. Geneva,
World Health Organization, 2002.
59
60
7
ACCESS TO ESSENTIAL MEDICINES
SUMMARY
Although the percentage of the worlds population without access to essential
medicines has fallen from an estimated 37% in 1987 to around 30% in 1999, the
total number of people without access remains between 1.3 and 2.1 billion people.
Lack of access is particularly concentrated in Africa and India.
Access to essential medicines appears closely correlated with other indicators of
selecting their medicines and are more likely to use these to limit procurement
choices than are high-income countries.
Generic competition and differential pricing can contribute substantially to the
pricing schemes may help countries obtain better purchasing prices for medicines.
Greater scope for domestic price regulation exists in many low-income countries.
7.1
61
TABLE 7.1
Low to
medium
access
(50%80%)
Medium
to high
access
(81%95%)
Very high
access
(<95% )
Number of
countries
Number of
countries
Number of
countries
Number of
countries
Total
Countries
Africa
Americas
Eastern Mediterranean
European
South-East Asia
Western Pacific
14
7
2
3
2
1
23
14
7
12
4
8
5
7
5
6
3
8
3
7
8
25
0
9
45
35
22
46
9
26
Total countries*
29
68
34
52
183
Even from these broad groupings the regional extremes are clear. In Europe, 25 of the 46
countries reporting were in the very high access group and only three countries were in
the very low access group, whilst in the African region only 3 of the 45 countries were in
the very high but 37 countries (over 80%) were in the very low and low to medium
groups.
Table 7.2 illustrates access in relation to population size.
TABLE 7.2
Number of
countries
Total population
(million)
%
of total
Population
without access
(millions)
267
(200334)
179
(134224)
143
(107179)
114
(85142)
127
(95159)
649
(487811)
55
(4169)
191
(143239)
47
(3559)
22
(1627)
29
(2236)
14
(1017)
26
(1932)
65
(4981)
14
(1017)
15
(1119)
15
(1119)
10
(812)
8
(610)
7
(59)
7
(59)
38
(2847)
3
(24)
11
(814)
1725
(12942156)
30
(2237)
100
African
45
566
10
American
35
813
14
East Mediterranean
22
485
European
46
832
14
South-East Asia
486
India
998
17
26
380
1274
22
183
5834
100
West Pacific
China
Total all countries
62
Percentage of world
population without
access
Table 7.2 shows that about 30% of the worlds population, or between 1.3 and 2.1 billion
people, are estimated not to have access to the essential medicines they need. In India, an
estimated 499649 million people (50% to 65% of the population) do not have regular
access to essential medicines. Throughout Africa, a further 267 million people (almost half
the population or 15% of the world total) also lack access.
Classifying access according to countries level of income, as in preceding chapters, shows
a clear relationship between economic level and access to medicines, as seen in Tables 7.3
and 7.4. Table 7.3 shows the medians and ranges of reported access figures from countries
by income level.
TABLE 7.3
Median reported
access level (%)
Low-income
Middle-income
High-income
60
85
100
Minimum
reported %
Maximum
reported %
10
30
98
93
100
100
Table 7.4 shows that the percentage of the population estimated to lack adequate access to
essential medicines is less than 1% in high-income countries, 39% in low-income countries and 24% in middle-income countries. The 1.3 billion people in low-income countries
estimated to lack access account for almost 80% of the total number of people in the world
who lack essential medicines.
TABLE 7.4
7.2
Number of
countries
Population
Number
(million)
Number
(million)
As % of
As % of
country
global total
income group without access
Low-income
Middle-income
High-income
63
86
34
3548
1447
859
1369
350
5
38.6
24.2
0.6
79.4
20.3
0.3
Total countries
and population
183
5854
1724
n.a
100
63
access levels. Well-performing health systems offer high levels of access, and poorly
performing ones result in large numbers of people being excluded from medicines as well
as other forms of treatment, prevention and care. Table 7.5 shows the relationship
between health outcomes in DALEs and access to medicines.
TABLE 7.5
51%80%
%
81%95%
Number of
countries
Number of
countries
>96%
%
Number of
countries
Total
Countries
Below 50 years
5059 years
60 years and over
18
5
6
62.0
17.0
21.0
22
13
17
42.3
25.0
32.7
9
12
21
21.4
28.6
50.0
1
5
52
1.7
8.6
89.7
50
35
96
Total countries
29
100
52
100
42
100
58
100
181
Table 7.5 shows that most countries reporting low access to medicines also had very low
disability-adjusted life expectancy. At the other end of the spectrum, almost 90% of
countries with very high access to medicines also had the highest level of health outcome.
7.3
1
Rational
use
3
Sustainable
financing
ACCESS
2
Affordable
prices
4
Reliable
health and
supply systems
As Figure 7.1 makes clear, rational medicines selection processes should be in use, based on
national or local essential drugs lists and treatment guidelines; prices should be at levels
64
affordable by governments, health care providers and consumers; fair and sustainable
financing for the medicines component of health care should be ensured through adequate
funding levels and equitable prepayment mechanisms, such as government revenues or
social health insurance, to ensure that poor people do not face proportionally higher costs
than the better off; and finally, reliable health and supply systems need to be in place, incorporating an efficient and locally-appropriate mix of public and private service providers.
Failure in any one of these processes will jeopardize peoples access to medicines.
The financing aspects of access were discussed separately in Chapter 5. The remaining
sections of this chapter examine in turn the evidence on each of the other three components
of access.
7.4
RATIONAL SELECTION
Rational selection of medicines means choosing medicines appropriate to the countrys
health situation on the basis of their safety and cost-effectiveness. Institutionalizing
rational choice involves using essential medicines lists (EMLs), based on the best available
evidence on local disease burden, efficacy, safety and cost of treatment for those diseases.
However, there is a significant difference between having an EML and using it effectively.
WHO has developed model lists of essential medicines since 1977, which have served as a
reference for countries in the establishment of their own national EML. The first Model
List, published one year before the Alma Ata Declaration of Health for All, contained
around 200 active substances. Approximately every two years, WHO updates the List on
the basis of evidence presented to a committee of experts. Following the revision in March
2003, the Model List now contains 316 active substances.4,5,6
Figure 7.2 indicates that the number of countries which revised their national EML
increased from 1985 to 1999: from 5 to 60 among low-income countries; from 2 to 62
among middle-income countries; and from 0 to 9 among high-income countries.
FIGURE 7.2
60
60.0
Percentage
50.0
40.0
29
30.0
22
20.0
10.0
Low-income
Middle-income
1985
1990
1995
High-income
1999
65
Table 7.6 shows that there is a clear relationship between a countrys EML status and its
level of income. Less than 10% of low- and middle-income countries had not established
an EML in 1999, compared with over two-thirds of high-income countries. However,
institutional use of EMLs, by hospitals or health insurers is often widely practised in
high-income countries and likely to be under-represented in these figures.
TABLE 7.6
Middle-income
High-income
No. Countries
No. Countries
No. Countries
EML updated
within 5 years
EML updated
over 5 years
No EML /not known
47
75
70
74
11
31
13
21
17
18
24
69
Total
63
100
95
100
35
100
Table 7.7 shows that the number of items on a national EML tends to be associated with
the level of a countrys income: the median list size is 276 medicines in low-income
countries, 420 in middle-income countries and 903 in high-income countries.
TABLE 7.7
Low-income
Middle-income
High-income
Total
Countries
45
49
5
Median
number of
medicines
Minimum
number of
medicines
276
420
903
134
35
531
Maximum
number of
medicines
6000
2348
3280
Standard
deviation
911
450
1036
The following chapter analyses experiences, challenges and approaches to ensuring the
rational use of medicines, once they have been selected and purchased.
7.5
AFFORDABLE PRICES
The price of medicines plays an essential role in access to medicines. When a course of
treatment for peptic ulcer costs almost twice the monthly wage of a government employee, as
in Cameroon,7 it is clearly not generally affordable. Several strategies are available to
countries to influence price, and they fall into two main categories: (i) obtaining the best
possible price through the selection and purchasing process and (ii) ensuring price regulation throughout the supply chain from manufacturer or importer to patient.8 Many
countries use combinations of these two approaches in their attempt to keep medicine
prices down, though responses to the World Drug Survey indicate that almost 40% of
respondent countries (53/135) implement no price regulation policy at all.
66
TABLE 7.8
Limitation to EML
Number
Low-income
Middle-income
High-income
37
25
2
77
43
13
Total countries
64
47
TABLE 7.9
Low-income
Middle-income
High-income
22
40
2
Median % by
international
tender
Minimum
Maximum
91
80
54
10
1
8
100
100
100
For patented medicines, international competitive tenders are seldom possible and
purchases have to be negotiated on a country-by-country and medicine-by-medicine basis.
The price offered by the manufacture is likely to vary according to the size of the country,
its level of income and local manufacturing capacity. Many countries lack the ability to
negotiate medicine prices in a professional, evidence-based way. In this situation, access to
price information by purchasers in all sectors may have a crucial role to play in successful
negotiated purchases. Prices of therapeutic competitors, where these exist, can help
purchasers assess value for money. In addition, prices paid in other markets may provide
useful evidence as to what a particular manufacturer is getting elsewhere for a particular
medicine with patent protection. A number of countries use international reference prices
systematically in their medicines purchasing and a number of price information services,
both national and international, are now available.i Pricing practice in Greece, for
i
A regularly updated list of this can be consulted on the WHO website: http://www.who.int/medicines/organization/
par/ipc/drugpriceinfo.shtml
67
example, takes account of prices for the same medicine in the three lowest-priced countries in the European Union. Prices for the most clinically effective new medicines in
France are set with reference to prices in four other European countries.9 Eight other
OECD countries take formal account of prices elsewhere.10,11 Figure 7.3 shows some of
these price information links.
FIGURE 7.3
Source: E. Schoonveldt
In a small but growing number of mainly high-income countries, systematic use is made
of pharmacoeconomic analysis in assessing and negotiating medicine prices. This entails
rigorous comparison of the clinical effectiveness of a new medicine, and its price, with the
effectiveness and price of the closest existing alternative medicine. In this way, public
purchasing bodies can assemble the evidence on cost-effectiveness in a systematic manner,
and judge whether the therapeutic advantage of a new medicine offsets its additional cost.
The Australian governments Pharmaceutical Benefits Scheme pioneered the use of this
approach, and since 1993 has used it to determine which new medicines will qualify for
insurance reimbursement. Countries including the Netherlands, UK and France employ
similar techniques in evaluating new medicines for public purchase and reimbursement.
As Chapter 4 illustrates, generic medicines, particularly unbranded generics, are usually
much less expensive than newer patented medicines, and in both high- and low-income
countries many governments encourage their use to control overall costs. In value terms,
the USA is the leading consumer of generic medicines in the world, as Chapter 4 shows.
But the use of generic medicines offers important opportunities for low-income countries,
where over the half of households live below the poverty threshold, to maintain affordable
access to medicines.
68
A study carried out in Ghana and Cambodia highlights the brand premium or gap
between prices of generic and brand medicines. Systematic surveys of the price of generic
and brand medicines were carried out in public health, private for-profit facilities, private
not-for-profit facilities (NGOs/religious missions) and private retail outlets (private
pharmacies). These surveys were based on 30 essential medicines (20 essential medicines
selected for diseases that are common throughout the world and 10 medicines that each
country selected according to the local disease situation). Figure 7.4 indicates that prices
vary greatly between generic and brand medicines. In Ghana, brand medicines are much
more expensive than generic medicines by a factor of 18 in public facilities, 11 in private
facilities, and 10 in private pharmacies but by only 50% more in the pharmacies of NGOs
and religious missions.12 In Cambodia, price differences between brand and generic
medicines are higher in private pharmacies than others: a two to threefold brand premium in private pharmacies, and in private facilities, and about 100% in public facilities
and in the pharmacies of NGOs and missions.
FIGURE 7.4
1779
1600
Percentage
1400
1200
1111
1044
1000
800
600
400
200
304
243
117
54
114
Ghana
Public
facilities
Cambodia
Private
facilities
NGO/
mission
Private
pharmacy
Using a slightly different approach but based on systematic surveys, brand and generic
prices for a fixed list of essential medicines were also compared in five other low- and
middle-income countries. Figure 7.5 shows that for one diuretic medicine, furosemide,
local retail prices ranged from a high of over 100 times the international reference price
(South Africa and Kenya, brand) to slightly below it (Sri Lanka, generic). For the full set of
medicines compared, generic prices were close to international reference prices in Kenya,
Sri Lanka and Armenia, while half of the innovator medicines in South Africa cost from
11 to 62 times the reference prices.
Clearly, big price differences exist not only between generic and innovator medicines, but
also between prices for the same brand or generic in different countries. Many countries
thus have considerable scope for taking steps to ensure that they are not paying more than
necessary for their essential medicines. National, regional or even global bulk purchasing
schemes greatly improve the prospect for achieving lower prices. Regional medicine
purchasing schemes exist in francophone West Africa, in the Caribbean, in Latin
America through the WHO/PAHO revolving drug fund, and in the countries of the Gulf
69
FIGURE 7.5
108.9
107.9
100
Percentage
80
60
40
24.6
24.4 21.0
20
3.7
2.7
0
0.8
6.1
3.0
-20
South Africa
Kenya
Sri Lanka
Brand
Armenia
Brazil
Generic
7.5.1
70
http://www.accessmed-msf.org/prod/publications.asp
This voluntary approach has had only a modest impact on peoples access to care. Although about 60 000 patients in Africa are reported to be receiving medicines through the
programme, they represent less than 1% of the HIV-infected population in need of
treatment. Moreover, demand from countries for medicines under this initiative is
limited, as cheaper generic sources of supply are increasingly available.13 Finally, countries
have little control over voluntary price discounts in terms of which medicines are
available, over what period, through which channels, and in what volume.
An alternative gesture by patent-holding manufacturers is to offer patent waivers. Commitment by the patent holder not to prosecute low-income countries for patent infringement would open the door to differential pricing. Such waivers have, in fact, already been
granted for African countries by at least one company for a limited range of products.
The WTO Ministerial Declaration on the TRIPS Agreement and Public Health has in
effect given a limited patent waiver for the least-developed countries by extending their
transition period with respect to pharmaceutical products to at least 2016.i
A more systematic approach to lower prices for the poorer countries might be achieved by
low- and high-income country governments working together with manufacturers and
consumer groups through an explicit differential pricing framework, as outlined in recent
publications.ii The common concern in these has been to establish more thorough market
segmentation between high-income and an identified group of low-income countries,
entailing the cooperation of manufacturers and governments in both high- and lowincome countries. Prices related to countries purchasing power would be the target for
new essential medicines, and measures (by both manufacturers and governments)
established to prevent exportation of differentially priced medicines to higher price
regions would be necessary. Regulatory mechanisms in high-income countries already
exist to prevent such reimportation. Mechanisms such as bulk purchasing could help to
guarantee both financing and volume for manufacturers.
7.5.2
Declaration on the TRIPS Agreement and Public Health. Ministerial Conference, Fourth Session. Doha, 914 November
2001, WT/MIN(01)/DEC/W/2, 14 November 2001. It should be noted, however, that the 48 Least Developed Countries,
as specified by the United Nations, account for less than 650 million people, less than half of the worlds poor, and only
one major pharmaceutical production country (Bangladesh).
ii
http://www.who.int/medicines/library/edm_general/who-wto-hosbjor/who-wto-hosbjor.html
and Report to the Prime Minister: UK working group on increasing access to essential medicines in the developing world. Department
for International Development, London, November 2002.
71
TABLE 7.10
None
Producer
price
Retail
mark-ups
Wholesale
mark-ups
Retail +
wholesale
mark-ups
Producer
price +
retail
mark-ups
Producer
price +
retail +
wholesale
mark-ups
Total
number of
respondents
and
percentage
Number of
countries
Percentage
54
10
15
20
10
122
44.3
8.2
12.3
5.7
16.4
4.9
8.2
100
When the data are analysed by country income level (Table 7.11), only 22% (4 of 18) of
high-income countries responding use no price regulation, whereas around half of lowand middle-income countries (50/104) do not regulate prices. Proportionally twice as
many high-income countries (22%) as low- and middle-income respondents (10%) use all
of the identified regulatory approaches and combinations surveyed to control domestic
prices. In both purchasing practices and in domestic price regulation measures many lowand middle-income countries appear to be missing opportunities to ensure that medicine
prices are affordable.
TABLE 7.11
None
Producer
price only
Low-income
Middle-income
High-income
Total
20
30
4
54
2
4
4
10
Retail
mark-ups
8
7
0
15
Wholesale
mark-ups
Retail and
wholesale
mark-ups
Producer
price + retail
mark-ups
All
Total
0
4
3
7
6
12
2
20
1
4
1
6
2
4
4
10
39
65
18
122
7.6
72
separate data for each sector (public, NGO, private health facilities and private dispensaries). All sectors in each country had expired items in stock, with the lowest level of
expired stock (16%) at NGO facilities in Tanzania and the highest, also at NGO facilities
(82%), in Rajasthan. All sectors in Rajasthan compared poorly with those in Tanzania.
Private health facilities (hospitals, clinics) compared poorly: in three of the four countries
they had the lowest percentage of unexpired key items in stock, though private pharmacies everywhere appeared to have better distribution systems.
FIGURE 7.6
84.0
79.0
80.0
Percentage
60.0
72.0
68.0
66.8
70.0
67.0
67.0 66.0
57.3 56.4
51.1
50.4
50.0
42.6
40.0
40.0
34.3
30.0
18.0
20.0
10.0
0
Cambodia
Ghana
Public
facilities
Rajasthan (India)
Private
facilities
Private
pharmacies
Tanzania
NGO/
mission
Source: MSH
FIGURE 7.7
Percentage
80.0
60.0
84.3 84.6
80.0
98.0
93.0
93.0
87.8
91.0
85.0
78.0
59.0
58.0
73.0
63.0
50.4
40.0
20.0
0
Cambodia
El Salvador
Public
facilities
Ghana
Private
facilities
Rajasthan (India)
Tanzania
NGO/
mission
Another indicator of the performance of the supply system is the percentage of prescribed
items which are actually dispensed. A low percentage of dispensing of prescribed items
may result from either out-of-stock facilities or unaffordable prices. Figure 7.7 uses
73
limited survey data from public, private for-profit and private not-for-profit facilities in
four countries and in one state in India to show the percentage of prescribed items actually
dispensed at facilities in each sector. The findings indicate that in Ghana, Tanzania and
Rajasthan, India, the public facilities perform less well than those in other sectors, while
in Cambodia the reverse is true. In Cambodia, NGO and private facilities are able to
dispense only 50% and 59% respectively of prescribed medicines.
REFERENCES
1
WHO medicines strategy: framework for action in essential drugs and medicines policy 20002003. Geneva, World
Health Organization, 2000.
The world health report 2000. Health systems: improving performance. Geneva, World Health Organization,
2000.
Laing R, Waning B, Gray A, Ford N, t Hoen E. 25 years of the WHO essential medicines lists: progress
and challenges. Lancet 2003, May 17:17239.
WHO model list of essential medicines, 13th list (April 2003), (http://www.who.int/medicines/organization/
par/edl/eml.shtml).
The selection and use of essential medicines. Report of the WHO Expert Committee, including the Model
List of Essential Drugs, thirteenth list (WHO Technical Report Series 920) in press, (http://www.
who.int/medicines/organization/par/edl/expertcomm13.shtml).
Are medicine prices a problem? Essential Drugs Monitor No.33, Geneva, World Health Organization, 2003.
Cost-containment mechanisms for essential medicines, including antiretrovirals, in China. Geneva, World Health
Organization, 2003.
10 Pharmaceutical price regulation: the current debate. London, Institute for Fiscal Studies,
(http://www.ifs.org.uk).
11 Jacobzone S. Pharmaceutical policies in OECD countries: reconciling social and industrial goals. Paris, OECD,
2000. DEELSA/ELSA/WD(2000)1.
12 Strategies for enhancing access to medicines. Boston, Management Sciences for Health, (http://www.
msh.org/seam/3.1.3.htm).
13 Grace C. Equitable pricing of newer essential medicines for developing countries. Geneva, World Health
Organization, 2002, (available electronically at: http://www.who.int/medicines/library/par/
equitable_pricing.doc).
14 Quick JD, Rankin JR, Laing RO, OConnor RW, Hogerzeil HV, Dukes MNG, Garnett A, eds. Managing
drug supply. West Hartford, CT, Kumarian Press, 1997.
74
8
RATIONAL USE OF MEDICINES
SUMMARY
Worldwide, it is estimated that half of all medicines are inappropriately prescribed,
dispensed or sold, and that half of all patients fail to take their medicine properly.
An estimated two-thirds of global antibiotic sales occur without any prescription,
and studies in Indonesia, Pakistan and India show that over 70% of patients were
prescribed antibiotics. The great majority up to 90% of injections are estimated
to be unnecessary.
The inappropriate use of medicines is not only widespread, it is costly and ex-
tremely harmful both to the individual and the population as a whole. Adverse
drug events rank among the top 10 causes of death in the USA and are estimated
to cost that country between US$ 30 and US$ 130 billion each year.
Growing resistance to antimicrobial medicines is a particularly serious challenge in
countries at all economic levels, and results largely from inappropriate prescribing
and use. For the treatment of malaria, chloroquine resistance is now established in
81 of the 92 countries in which the disease is endemic.
Much greater use of evidence-based diagnostic and treatment guidelines by health
professionals is needed.
More effective monitoring and regulation of medicines, and public education and
8.1
INTRODUCTION
Worldwide, it is estimated that over half of all medicines are prescribed, dispensed or
sold inappropriately, and that half of all patients fail to take their medicine correctly.1,2
Medicines are used rationally when patients receive the appropriate medicines, in doses
that meet their own individual requirements, for an adequate period of time, and at the
lowest cost both to them and their community.2,3 Irrational use occurs when one (or
more) of these conditions is not met.
In spite of available tools and information on how to measure medicines use and the
intervention strategies needed to achieve this, irrational use continues to occur. This is
wasteful, expensive and dangerous, both to the health of the individual patient and to the
population as a whole. Inappropriate use of medicines, and the related illness and deaths,
are not restricted to low-income countries. Studies in Canada, Australia, Kuwait and the
USA, as well as in middle-income countries such as South Africa and Thailand, have
revealed that inappropriate use of medicines is widespread in teaching hospitals1. In many
countries, the problem extends well beyond hospitals. Two-thirds of all antibiotics are
sold without prescription, through under-regulated private sectors. A recent review of
adverse drug events in the USA4 shows these to be the fourth to sixth ranked cause of
death in that country, with economic costs of between US$ 30 to US$ 130 billion per year.
75
In many countries, the problem is entrenched. Few countries currently monitor inappropriate use of medicines partly due to a lack of awareness of the scale of the problem and
its economic and health costs and decision-makers often lack knowledge of the most
cost-effective ways to tackle this problem. Meanwhile, some countries lack the financial
and human resources needed to promote more accurate diagnostic procedures, to implement effective regulation of prescribing and dispensing behaviour and to promote
adherence to treatment by patients, in both the public and private sectors. In addition, the
high cost of medicines contributes to low adherence levels by patients: in some studies, an
estimated 90% of consumers buy three days supply, or less, of antibiotics, making compliance with the recommended dosage impossible.5,6
Institutions, health professionals and patients all have roles to play in promoting more
rational use of drugs. Effective regulation, clear clinical guidance, supportive incentive
structures, training, education and management, are key components of an effective
policy in this area.
8.2
In most developed countries, research on medicines use is routine in health care facilities
and numerous studies have demonstrated its effectiveness.7 However, most developing
countries do not have data on this at the national level.
A recent article by Ronning et al reviewed antibacterial usage in 16 European countries.
This study demonstrated that despite the countries being very similar economically and
epidemiologically the use varied by a factor of 2.5 between countries.8
76
Pharmacoepidemiology, the study of the utilization and effects of drugs in large numbers
of people is also crucial in the promotion of rational drug use. These studies use information on medicines use to estimate the likely beneficial and adverse effects of medicines in
populations. This kind of information is provided by the International Society for
Pharmacoepidemiology.9,10
A major step towards rational use of medicines was the launch by WHO in 1977 of the 1st
Model List of Essential Drugs, designed to help countries formulate their own national
lists. In 1989, the International Network for the Rational Use of Drugs (INRUD) was
formed to conduct multidisciplinary intervention research to promote the rational use of
medicines.7 In 1993, WHO and INRUD developed and published a standard methodology for selected drug use indicators in health facilities.11,12 Since then, several intervention
studies have been conducted using these indicators, and a review of the published studies
with adequate study design was presented at the 1st International Conference for
Improving the Use of Medicines (ICIUM) in Thailand in 1997.
Box 8.1 shows the selected WHO/INRUD drug use indicators for health care facilities.
These indicators can be used to identify problems in general prescribing and quality of
care at these facilities. Results from the use of these indicators can help identify the
motives for irrational use and other problems in the use of medicines. The data collected
can then be used to design appropriate interventions and to measure the impact of those
interventions.1114
BOX 8.1
Facility indicators
77
8.3
8.3.1
TABLE 8.1
%
Antibiotics
%
Injections
%
Generic
%
EML
35
35
34
26
2.39
4.4
1.3
44.8%
76.5%
22%
22.8%
74%
0.2%
60.3%
99%
24.6%
71.7%
99.6%
12%
4.5
4.0
Number
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Yem
Ug en (1
and 99
8
Sud a (199 )
Ma an (19 0)
Ind lawi 91)
o
(
Ind nesia 1991)
Ban ones (1988
gla ia (1 )
Zim desh 991
)
b
Zim abw (1991
e
)
b
Zim abwe (1991
)
Zim babw (1995
bab e (1 )
998
w
Tan e (2 )
zan 00
2
i
Nig a (199 )
2
e
Nig r (199 )
Ecu er (1 2)
a
9
Ecu dor (1 92)
ado 992
r (1 )
Gu 994
ate
)
Ma
m
ced Came ala
on
r
Pak ia (2 oon
ista 00
Erit n (19 0)
9
re
Erit a (19 8)
rea 92)
Erit (19
95
re
Ind
ia Nig a (1 )
Ind -Karn eria ( 997)
i
2
a
a
Ind -Ka taka 001
ia-W rna
(2 )
es taka 002
Uzb t Beng (200 )
eki al (1 2)
s
9
Na tan (2 99)
m
0
Na ibia (1 00)
m
9
Na ibia ( 94)
mib 199
Mo Nami ia (19 7)
zam bia 99)
biq (200
Sul
ue
1
t an
ate Gha (199 )
of O na ( 3)
1
9
ma
n (2 93)
002
)
Country
78
% antibiotics
80
70
Percentage
60
50
40
30
20
10
Yem
Ug en (1
and 99
8
Sud a (199 )
Ma an (19 0)
Ind lawi 91)
o
(
Ind nesia 1991)
Ban ones (1988
ia
g
)
Zim ladesh (1991
)
b
Zim abw (1991
bab e (19 )
Zim we 91
)
Zim babw (1995
bab e (1 )
998
w
Tan e (2 )
zan 00
2
i
Nig a (199 )
2
e
Nig r (199 )
Ecu er (1 2)
ado 992
Ecu
r
ado (1992)
r
)
Gu (1994
ate
)
Ma
m
C
ced ame ala
o
r
Pak nia (2 oon
ista 000
n
Erit (19 )
9
re
Erit a (19 8)
9
re
Erit a (19 2)
rea 95)
Ind
(1
N
ia
Ind -Karn iger 997)
Ind ia-Ka ataka (2001
ia-W rna
(2 )
es taka 002
Uzb t Beng (200 )
eki al (1 2)
s
9
Na tan (2 99)
m
0
Na ibia (1 00)
m
9
Na ibia ( 94)
mib 199
N
i
a
Mo ami (19 7)
zam bia 99)
biq (200
Sul
ue
1
t an
ate Gha (199 )
of O na ( 3)
ma 1993
n (2 )
002
)
Country
Analysis of data from Uzbekistan, Pakistan, Indonesia and Eritrea revealed that 75%99%
of patients diagnosed with an upper respiratory tract infection (URTI) received antibiotics.1619 In Eritrea, for example, it was confirmed that 75% of the adults and children
diagnosed with URTI were prescribed antibiotics even though the cause of the infection
may have been viral.16 Results from Indonesia demonstrated that 46% of patients aged
under five years received oral rehydration salts (ORS) for the treatment of diarrhoea while
73% of these same patients received oral antibiotics. Among patients aged over five years,
36% received ORS, 91% received oral antibiotics, and 25% of patients received an antibiotic injection.17
Indicator: Percentage of patients prescribed injections
Figure 8.3 shows the percentage of patients receiving injections. On average over 23% of
consultations resulted in an injection. Countries with the highest percentage of injections
(over 60%) included Indonesia (1988), Pakistan, Uzbekistan and Ghana.1519 However,
a serial survey in an area of Indonesia in 1991 revealed that injection use had improved
significantly and the percentage of patients prescribed injections had been reduced to
17%.17 Overall, it is estimated that up to 90% of injections are unnecessary, because
alternative, safer routes of administration are available.17 Study results from Uzbekistan
revealed that excessive injection prescribing occurred mainly for: URTI (54.8%); urinary
tract infection (79.8%); anaemia (32.2%); digestive disorders, including diarrhoea
(47.7%); and hypertension (68.9%).18
79
FIGURE 8.3
% injectables
70
Percentage
60
50
40
30
20
10
Yem
Ug en (1
and 99
8
Sud a (199 )
Ma an (19 0)
Ind lawi 91)
o
(
Ind nesia 1991)
Ban ones (1988
ia
g
)
Zim ladesh (1991
)
b
Zim abw (1991
e
)
b
Zim abwe (1991
)
Zim babw (1995
bab e (1 )
9
Tan we (2 98)
zan 00
Nig ia (19 2)
er
92
Ne ia (19 )
Ecu pal (1 92)
a
9
Ecu dor (1 92)
ado 992
r
)
Gu (1994
ate
)
Ma
ma
C
a
ced me la
o
r
Pak nia (2 oon
ista 000
n
Erit (19 )
9
re
Erit a (19 8)
9
re
Erit a (19 2)
95
re
Ind
ia-K Nig a (199 )
Ind arn er
7)
Ind ia-Ka ataka (2001
ia-W rna
(20 )
t
a
es
ka 02
Uzb t Beng (200 )
eki al (1 2)
st a
9
Na n (2 99)
mib 00
Na ia (1 0)
m
9
Na ibia ( 94)
mib 199
N
i
a
a
Mo mi (19 7)
zam bia 99)
biq (200
Sul
ue
1
t an
ate Gha (199 )
of O na ( 3)
1
ma 993
n (2 )
002
)
Country
Results from Eritrea also indicated the percentage of irrational use of injections for specific
diseases (with no significant difference between overall results and results by age or
province).16 Results of the study are shown in Figure 8.4.
FIGURE 8.4
10
12
14
16
18
20
Percentage
% generics
100
Percentage
80
60
40
20
Ind
Sud
an
(19
on
91
Zim esia (1 )
991
bab
)
we
Zim
bab (1991
w
)
Zim
e (1
99
ba
Zim bwe ( 5)
199
bab
8)
w
Tan e (200
zan
2)
ia (
19
Nig
eria 92)
(
199
Ne
2)
p
Ecu al (199
ado
2)
r (1
Ecu
ado 992)
r (1
994
Gu
)
Pak atem
ala
ista
n
Erit (1998
)
rea
Erit (1992
rea
)
(19
Ind
E
ia-K ritrea 95)
(19
Ind arnat
97)
ak
ia
Ind -Karna a (20
0
ia-W
t ak
2
a (2 )
est
002
B
)
Uzb engal
(19
eki
9
st a
n (2 9)
Na
mib 000)
Na ia (199
mib
4)
ia (
Na
mib 1997)
ia (
Na
19
Mo mibia 99)
zam
(20
biq
01)
ue
(19
Gh
ana 93)
(19
93)
Country
% EML
100
60
40
20
Na
(2 mibi
00 a
1)
be
(2 kista
00 n
0)
Uz
Country
Be Ind
ng ia
al -W
(19 es
99 t
)
Er
(19 itre
95 a
)
Pa
k
(19 istan
98
)
N
(19 epa
92 l
)
Ta
nz
(19 ania
92
)
0
Zim
b
(2 abw
00 e
2)
Percentage
80
81
8.3.2
TABLE 8.2
Count
Mean
Maximum
Minimum
10
4.0
6.3
2.3
105
204
12.5
12
89%
100%
70%
54%
89.7%
20%
16
71.4%
98.6%
27%
Zimbabwe conducted serial surveys on patient care indicators from 1995 to 2000, which
were then compared. Information was collected on patients knowledge of their medicines in relation to the dose, frequency, duration and indication. The study revealed that over
70% of patients were knowledgeable about the dose, frequency and indication the same
as in previous years. However, the study identified a need for greater emphasis in staff
training on the importance of telling patients the duration of their treatment. The Zimbabwe study also reported on the average time patients spent in consultation with prescribers. The time was measured for a range of prescribers at the institutions, including doctors
and nurses. The average consultation time was five minutes per patient. The average
dispensing time was 2.5 minutes and the dispensers included pharmacists, pharmacy
technicians, dispensary assistants, nurses and auxiliary nurses.27
Very few countries reported data on the percentage of drugs that were adequately labelled.
Of the eight countries that did so, the average was 54%. Zimbabwe carried out additional
analysis of the labelling by collecting information on the name of the drug, the strength,
quantity, dose and the date dispensed, as well as the name of the patient and health
facility. The results reflected a need to include on the label the strength of the medicine,
the date dispensed and the name of the patient and health facility.27
8.3.3
Facility indicators
Indicator: Percentage of health facilities with an essential medicines list
Only nine studies reported information on the percentage of health facilities with an
essential medicines list but these do not indicate the level of the facilities involved. On
average, 78% of the facilities had an essential medicines list. However, in Ecuador, only
38% of facilities had an essential medicines list.
82
FIGURE 8.7
% EML
100
Percentage
80
60
40
20
N
(2 ige
00 r
1)
Er
(19 itre
95 a
)
Ec
u
(19 ado
94 r
)
N
(19 epa
92 l
)
Ni
g
(19 eria
92
)
Ta
nz
(19 ania
92
)
b
(2 a b w
00 e
2)
Zim
ba
(19 bwe
98
)
Zim
M
(19alaw
99 i
)
Country
% EML
90
80
Percentage
70
60
50
40
30
20
10
Ec
u
(19 ado
92 r
)
N
(19 epa
92 l
)
Ni
g
(19 eria
92
)
Ta
nz
(19 ania
92
)
M
a
(19 law
92 i
)
Zim
b
(2 abw
00 e
2)
Country
83
BOX 8.2
Serial surveys
Three countries, Namibia, Zimbabwe and Eritrea, conducted serial surveys for monitoring purposes. Serial surveys can be useful in the evaluation of rational prescribing at
baseline and to determine the success of subsequent prescribing as a result of specific
strategies. For example, results from Namibia show that the average number of drugs
prescribed per patient was higher than in previous years and that the use of the essential
medicines list had improved. However, the percentage of generic prescribing had not
improved and the percentage of antibiotics prescribed had increased. Many low-income
countries such as these have been hard hit by the HIV/AIDS epidemic which may
account for the increased number of drugs prescribed per patient, including the number
of antibiotics and injections prescribed. Since no information is available to confirm this,
future serial surveys should aim to incorporate this.
8.3.4
TABLE 8.3
1.71
2.4
2.96
2.64
2.54
2.24
2.61
14%
18%
30%
10%
14%
15%
*83%
14%
29%
9%
0%
25%
23%
21%
0%
2%
3%
6%
7%
6%
1%
*Analysis of the results shows that the high percentage of medicines written as generics in
the suburban health centre (facility G) reflects the fact that this was the first computerized
facility studied and drugs appear automatically by generic name.
8.4
84
10
12
Percentage
85
TABLE 8.4
Respiratory
URTI
Anaemia
Digestive,
incl. diarrhoea
Hypertension
3.2
2.9
2.2
2.6
3.1
47.3
38.3
17.9
18.8
16.7
83
78.5
60.6
79.4
79
78.9
93.5
1.7
30.2
2.2
54.8
79
32.2
47.7
68.9
Average
no. of drugs
Percentage
of generics
Percentage
from EML
Percentage
with antibiotic
Percentage
with injection
Elsewhere, in Pakistan, results shown by level of care, district and age group reveal that
both antibiotics and injections are over-prescribed in each of these categories, as shown in
Table 8.5.17 In general the differences between levels, districts and age groups are small.
TABLE 8.5
Percentage
from EML
Level of care
Rural health centre
Basic health centre
3.2
3.7
38
33
78
75
74
73
72
68
3.4
3.6
3.5
34
37
35
75
75
79
72
74
75
66
74
71
01 years
14 years
514 years
1545 years
>45 years
2.4
3.1
3.4
3.7
4
33
34
37
35
37
72
84
84
69
72
22
65
78
81
85
74
72
70
70
66
Average
3.5
35
76
74
70
District
Larkhana
Thar
Surkur
Age group
86
FIGURE 8.10
20
40
60
80
100
120
Percentage
Percentage injection
8.5
Percentage of antibiotics
ANTIMICROBIAL RESISTANCE
Overuse and misuse of antimicrobials are contributing to growing resistance to treatment
for the very diseases that contribute most to the burden of illness in low-income countries.
Resistance to the use of chloroquine for the treatment of malaria, for example, is now
established in 81 of the 92 countries where the disease is endemic substantially raising
FIGURE 8.11
Chloroquine
Sulfadoxinepyrimethamine (Fansidar)
Multi-drug resistance
87
the costs of treatment with second- and third-line antimalarial medicines. Figure 8.11
shows the distribution and reported resistance to antimalarials.
Estimates of resistance to primary multi-drug therapy for tuberculosis from 28 countries at
all income levels range from a low of 2% to a high of 40% of cases.31 Resistance to penicillin treatment is estimated to be between 5% and 98% for gonorrhoea (N. gonorrhoeae)32
and between 12% and 55% for pneumonia and bacterial meningitis.33
In Bangladesh, resistance to ampicillin in the treatment of shigellosis diarrhoea is estimated to be over 90%. In addition, resistance to treatment with nalidixic acid increased
from less than 10% in 1987 to over 90% in 1992.34 A study of antibiotics use in 13 countries
from 1992 to 1996 revealed that antibiotics were wrongly prescribed for approximately
30% of cases of URTI. More recently, studies in low-, middle- and high-income countries
showed that antibiotics were wrongly prescribed in 50% to almost 100% of URTI cases.
Elsewhere, a large study in the USA (JAMA 1997) found that 51% of patients with colds
and URTI were receiving antibiotics and estimated that over 20% of all antibiotic prescriptions were clinically useless.35 The highest overall rate for the use of antibiotics for
URTI was 97% in China (1997).36 Yet in 1994, only 8% of cases were found to be treated
with antibiotics. One important change in the intervening period was the increasing
dependence of health providers on revenue from sales of medicines to supplement low
incomes. Perverse financial incentives almost certainly have a role to play in Chinas
recent irrational use of antibiotics and in the development of antimicrobial resistance.
Similar trends have been identified in other countries, particularly those in transition to
market economies.
Antimicrobial resistance is not only a problem for the individual patient, it also reduces
the effectiveness of established treatment and poses a major threat to public health
by increasing the complexity and cost of treatment and reducing the probability of a
successful outcome.
BOX 8.3
88
clinical guidelines
Table 8.6 indicates that standard treatment guidelines do not exist in a majority of
WHOs Member States.
TABLE 8.6
Number of countries
Percentage
STGs revised
within last 5 years
55
28.5%
STGs over
5 years old
No STGs/
unknown
Total
32
16.6%
106
54.9%
193
100%
Where countries do have STGs, their use is not always adequately supported by training,
information and incentives. Survey results included in the WHO database on rational use
of medicines indicate that the percentage of prescriptions conforming to guidelines in
nine countries varied between a low of 25% and a high of 59%.37
8.5
89
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4 White TJ, Araekelian A, Rho JP. Counting the costs of drug-related adverse events. Pharmacoeconomics,
1999; 15(5): 445458.
5 Lansang M, Lucas-Aquino R, Tupasi T, et al. Purchase of antibiotics without prescription in Manila, the
Philippines: inappropriate choices and doses. Journal of Clinical Epidemiology, 1990; 43(1):6167.
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7 Proceedings of the twentieth anniversary symposium. ATC/DDD classification. WHO Collaborating Centre for
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antibacterials. Berlin, Springer-Verlag. 2003.
9 Dukes MNG, ed. Drug utilization studies. Methods and uses. WHO, European Series No.45. Copenhagen,
World Health Organization, Regional Office for Europe, 1993.
10 International Society for Pharmacoepidemiology, (http://pharmacoepi.org).
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1993.
12 Quick JD, Rankin JR, Laing RO, OConnor RW, Hogerzeil HV, Dukes MNG, Garnett A, (eds). Managing
drug supply. 2nd ed. West Hartford, CT, Kumarian Press, 1997.
13 Ross-Degnan D, Laing RO, Quick J, et al. A strategy for promoting improved pharmaceutical use: the
International Network for Rational Use of Drugs. Soc. Sci. Med. 1992; 35:132941.
14 Hogerzeil HV, et al. Field-tests for rational drugs use in twelve developing countries. Lancet 1993; 342:
14081410.
15 Embaye A. Drug use studies in Eritrean health facilities. September 1999, (http://dcc2.bumc.bu.edu/richardl/
IH820/Embaye_concentration_paper.htm).
16 Arustiyono. Promoting rational use of drugs at the community health centres in Indonesia, (http://dcc2.
bumc.bu.edu/prdu/Other_Documents/ARUS_INDONESIA_PRDU.htm).
17 Pavin M, et al. Prescribing practices of rural primary health care physicians in Uzbekistan. Trop Med. & Int.
Health, 2003;8 (2):182190.
18 Memon K. Use of drugs in Sind Province Pakistan primary health care facilities. (http://dcc2.bumc.bu.edu/
prdu/Other_Documents/Khalil_Concentration_Paper.htm).
19 Chorliet S, Gulija M, Andreeva V. Drug use survey in Macedonia 2000. (http://dcc2.bumc.bu.edu/richardl/
IH820/Resource_materials/Drug_use_survey_in_Macedonia1.doc).
20 Lates J, Shiyandja N. Third national survey on the use of drugs in Namibias public health institutions including
monitoring the implementation of the National Drug Policy. July 2001. (http://dcc2.bumc.bu.edu/richardl/
IH820/Resource_materials/FINAL_Drug_use_survey_2001_Report.doc).
21 Groom A, Hedlund A. Promoting appropriate drug use in missionary health facilities in Cameroon. Geneva,
World Health Organization, 1998.
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22 Mallet PH, Njikam A, Scouflaire MS. valuation des habitudes de prescription et de lusage rationnel des
mdicaments au Niger. Enqutes successives dans 19 centres de sant intgrs de la rgion de Tahoua. Cahiers dtudes
et de recherches francophones / Sant, Vol. 11, Numro 3, MaiJuin 2001: 18593.
23 Srinivas SC, Chaudhury RC, Delhi Society for Promotion of Rational Use of Drugs, Karnataka State
Pharmacy Council, Bangalore. Results for rational drug use indicators for 8 government hospitals and 4 private
hospitals. 2002, E-mail correspondence.
24 Srinivas SC, Chaudhury RC, Delhi Society for Promotion of Rational Use of Drugs, Karnataka State
Pharmacy Council, Bangalore. Results for rational drug use indicators for 7 dispensaries of ESI in Karnataka.
2002, E-mail correspondence.
25 Hazra A, Tripathi SK, Alam MS. Prescribing and dispensing activities at the health facilities of a
non-governmental organization. Natl Med J India, 2000 JulAug; 13(4): 17782.
26 Gunn BC Sr, Ali SA. Drug utilization studies in the Sultanate of Oman. December 2002, E-mail
correspondence.
27 Public sector survey 2000. Harare, Directorate of Pharmacy Services Ministry of Health and Child Welfare.
Zimbabwe, 2000; p.3542.
28 Simonsen L, Kane A, Lloyd J, Zaffran M. Unsafe injections in the developing world and transmission of
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29 Mann J, et al. Risk factors for human immunodeficiency virus seropositivity among children 124 months
old in Kinshasa, Zaire. Lancet, 1986; 2(8508): 6547.
30 Report from the International Field Epidemiology Course, Chisanu, Moldova [editorial]. Weekly
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31 Espinal MA. Epidemiology of multi-drug resistant tuberculosis in low and middle income countries. In:
Bastian I, Portaels F, (eds), Multidrug-resistant tuberculosis. Dordrecht, the Netherlands, Kluwer Academic
Publishers, 2000.
32 Tapsall J. Antimicrobial resistance in Neisseria gonorrhoea. Geneva, World Health Organization, 2001. WHO/
CDS/CSR/DRS/2001.3.
33 Schrag S, Beall B, Dowell SF. Resistant pneumococcal infections: the burden of disease and challenges in monitoring
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34 Sack DA, et al. Antimicrobial resistance in shigellosis, cholera and campylabcater. Geneva, World Health
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35 Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for adults with colds, upper respiratory tract
infections, and bronchitis by ambulatory care physicians. JAMA, 1997, 278(11):9014.
36 Hui L, Li X, Zeng X, Dai Y, et al. Patterns and determinants of use of antibiotics for acute respiratory tract
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37 Holloway K. Measuring use of medicines. How have we progressed in the last decade? Presentation of results
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91
92
MEDICINES REGULATION
9
MEDICINES REGULATION
SUMMARY
Most countries have a medicines regulatory authority and formal requirements for
registering medicines. However, medicines regulatory authorities differ substantially in their human and financial resources, and in their overall effectiveness.
Fewer than one in six WHO Member States have well-developed drug regulation
and two in six have no or very little drug regulatory capacity.
The quality of medicines varies greatly, particularly in low-income countries, both
neglected.
Three types of common imbalance have been identified in regulatory practice:
9.1
INTRODUCTION
The production and distribution of medicines require public oversight and stewardship.
Unlike ordinary goods and services, an unregulated medicines market place will fail: it
will be not only inequitable, but also inefficient, and probably dangerous to public
health.1 Most countries recognize this need and many have done so for a long time: legal
guidelines on the use of drugs by physicians date from as far back as Egypts late Pharaonic
period.
The task of overseeing and regulating the medicines market place is often formidable.
Thousands of products may be available, supplied by large numbers of manufacturers and
handled by numerous importers, wholesalers and retailers. Three main components of
stewardship in the medicines market are identified in a recent review:2
product registration: assessing and authorizing products for market entry, and
monitoring their effectiveness and safety after entry
Institutional arrangements and the resource support for carrying out these components
differ widely among countries. If a national drug regulatory authority (DRA) is an arm
of an existing ministry, its director may not be able to make major policy decisions on
93
his/her own. It may well be that many drug regulation activities are carried out by
another agency with overlapping jurisdictions and functions.3 Delegation of tasks by a
DRA to external groups of experts or to subcommittees can be risky, as these outside
groups may acquire a considerable influence on the system as a whole:
this influence can make it hard to allocate tasks to a wider potential group of experts
the outside groups may acquire such authority that other experts routinely defer to
them, bypassing the NDRA procedures or at least, making balanced debate difficult.4
94
MEDICINES REGULATION
9.2
9.2.1
9.2.2
95
TABLE 9.1
1993
1994
27
22
22
15
26.5
20
19
18
8
23
14
13
29
19
18
16
7
19.3
11
15
16
16
17
12
7
18
22
14.5
29
17
15.5
13.8
6
18.6
20
15
34
17.5
17
2000
2001
12
6
18.2
14
6
18.1
EP = European Parliament
The limited data available for other countries (Table 9.2) suggest that average approval
times, even for new products, are often faster than in developed countries with the largest
pharmaceutical market share. In particular Costa Rica has approval times approaching 1.5
months.
TABLE 9.2
19951999
20002002
7
9
3
12
5
25
7
6
18
6
9.5
6
18
7
7
1.5
Algeria
Bulgaria
Costa Rica
Cuba
Cyprus
Czech Republic
Nigeria
Malaysia
Tunisia
Uganda
Uruguay
Venezuela
Zimbabwe
9.2.3
6
12
5
36
6
18
6
24
6
18
25.3
4.5
96
MEDICINES REGULATION
9.3
TABLE 9.3
Countries with law on (i) manufacturing and (ii) distribution (by income
groups)
Law on manufacturing
Low-income
Middle-income
High-income
Total
TABLE 9.4
Law on distribution
35 (55.6%)
53 (56.4%)
21 (60%)
36 (57.1%)
57 (60.6%)
22 (62.9%)
109 (56.8%)
115 (59.9%)
32 (50.8%)
52 (55.3%)
20 (57.1%)
38 (60.3%)
54 (57.4%)
17 (48.6%)
104 (54.2%)
109 (56.8%)
The rationale for regulating manufacturing and distribution is to ensure quality and
safety. Common steps taken by regulatory agencies to ensure quality include requirement
of proof of good manufacturing practices (GMP) during product registration, and
sampling and testing of medicines at the procurement or distribution stage. Responses to
questions on these practices in WHOs 1999 survey generated a composite indicator of
basic elements of quality control in place, which indicates that low-income countries
achieve somewhat less than middle- and high-income countries in this respect (Table 9.5).
97
TABLE 9.5
25 (39.7%)
43 (46.2%)
16 (45.7%)
Total
84 (44.7%)
BOX 9.1
In the early 1970s, a UK manufacturer produced an infusion fluid which caused the
death of five patients because it was heavily contaminated with bacteria. Before distributing the fluid, the manufacturer had tested several bottles and found them to be sterile.
Eventually a technical fault was found in the sterilizer. The bottles at the bottom had not
been properly sterilized. The bottles that the manufacturer had tested were from the
upper part, giving the false impression that all the bottles were sterile.
Source: Making a Difference: Manufacturing Quality Medicines. Quality Assurance. WHO/EDM/QSM/
2000.3
In the context of developing countries, a problem arises when a DRA (whose mission it is
to protect the public) takes it upon itself to perform GMP inspections. This is likely to
ensure duplication of effort and this is particularly resource-inefficient if the DRA merely
confirms a previous inspection failure. Developed countries already inspect large-scale
pharmaceutical manufacturers. Moreover, international health organizations insist on
GMP inspections as well. UNICEF, for instance, contracts out GMP inspection services by
arrangements with certain countries such as Australia and South Africa whose DRAs can
perform these services. At present, these UNICEF-associated GMP inspection reports are
not shared with developing country DRAs. Things are changing, however. In March 2002
WHO published its first list of prequalified manufacturers of AIDS drugsi (see also, below).
98
http://www.who.int/medicines/organization/qsm/activities/pilotproc/ppdoc1.doc
MEDICINES REGULATION
Most drug regulatory authorities determine frequencies for GMP inspection by considering the number of manufacturing plants. Australia, however, uses another system for
setting inspection frequency, based on product type and on manufacturer type. Products
are classified according to their relative therapeutic and side-effect risk, i.e. as high-risk,
medium-risk or low-risk. Similarly, manufacturers are categorized according to their
risk in passing GMP compliance, i.e. acceptable, marginal or unacceptable GMP. The
frequency of GMP inspection is a function of the product risk and manufacturer risk
profile. Frequent inspections are made of plants producing high-risk products.2
Regulation of drugs for export
Export laws of developed countries are sufficiently diverse that in some cases the criteria
for product export is not the same as for full licensing for use in the country.16
A drug that is eligible for commercial distribution within the United States generally
may be exported without any additional FDA approval or involvement. As to a product
intended for export that could not otherwise be commercially distributed within the
United States (i.e., is unapproved), the general rule is that the product may nevertheless
be exported if it: (a) accords to the specifications of the foreign purchaser, (b) is not in
conflict with the laws of the country of destination, (c) is labelled on the outside of the
shipping package that it is intended for export, and (d) is not sold or offered for sale in
domestic commerce. Thus, in a nutshell, the exporter shipping products from the United
States must comply either with FDAs laws or with the laws of the importing country
which may, or may not, be sufficiently comprehensive to assure safety.
However, the U.S. law does provide for export of unapproved products to highly developed countries presumably relying on the high quality review of these listed countries.
Listed countries are Australia, Canada, Israel, Japan, New Zealand, Switzerland, South
Africa, and the countries of the EU and the European Economic Area (EEA). Unapproved
drug exports must still meet FDA standards for GMP.
BOX 9.2
This high standard for exporting from the U.S. is not the case for other drug regulatory
systems. For example, Norplant implantable contraceptives were developed mainly
for use in developing countries, but first were approved for marketing in Finland in
1983 and in Sweden in 1985. Since then Norplant has been approved in more than 40
countries, most of them in the developing world. Ollila & Hemminki (l996)17 analysed
the Norplant clinical documentation submitted to the Finnish and Swedish drug
control authorities and concluded that the clinical data were of poor quality and were
mainly focused on assessing efficacy. Side-effects, acceptability, proper insertions and
removals, follow-up and other requirements of the health care system for proper use
of the implant in developing countries were poorly studied, if at all. This example of
Norplant licensing in Finland shows that licensing of drugs in industrialized countries
is not always sufficient to guarantee safety of new drugs in developing countries.
Greece does not allow unlicensed drugs to be exported but in Germany all exported
products should merely be safe and should not be misleadingly labelled. As of 1996,
drug exports from the Netherlands were not subject to any regulatory restriction.
Switzerland issues export-only licences.18 Most European countries do not have specific
procedures covering the export of drugs which have been rejected for licensing on the
domestic market.17 Austria, France, Germany, Greece and Spain do not allow the export
of rejected drugs, although exceptions may apply. Notwithstanding the above mentioned restrictions, many rejected drugs may remain unidentified. Drugs may disappear
from the market for a number of reasons, and it is often difficult to distinguish between
regulatory decisions and action taken by companies themselves.17
99
9.3.1
Quality of medicines
Recent survey data suggest there is cause for concern about the quality of medicines in the
distribution system in some countries, both in the public and private sectors. Table 9.6
shows the percentage failures of samples of two important antimalarial medicines:
chloroquine syrup and tablets and sulphadoxine/pyrimethamine tablets in seven countries.20 Average content failure for chloroquine syrup was 23% and for tablets 38%, with
TABLE 9.6
Chloroquine syrup
Gabon
Ghana
Mali
Kenya
Mozambique
Sudan
Zimbabwe
Average failure (%)
Range (%)
Source: C. Maponga, C. Ondari 20
100
Chloroquine tablets
Content
Content
0
(0/8)
5.0
(1/20)
66.7
(4/6)
25.0
(2/8)
25.0
(3/12)
26.6
(4/15
13.3
(2/15)
29.0
(5/17)
66.7
(12/18)
47.3
(9/19)
42.8
(3/7)
20.0
(3/15)
5.2
(1/19)
57.1
(8/14)
23.0
066.7
38.3
2066.7
Sulphadoxine/pyrimethamine tablets*
Dissolution
Content
Dissolution
5.8
(1/7)
20.0
(3/15)
5.2
(1/19)
28.6
(2/7)
6.7
(1/15)
12.5
(2/16)
7.1
(1/14)
0
(0/10)
37.5
(3/8)
0
(0/7)
0
(0/12)
5.5
(1/18)
0
(0/20)
10.0
(1/10)
75.0
(3/4)
100
(7/7)
91.7
(11/12)
100
(18/18)
80.0
(12/15)
100
(10/10)
12.2
5.228.6
7.6
037.5
91.1 (n=6)
75100 (n=6)
MEDICINES REGULATION
highs of 67% for both. While content failures for SP were much lower (average 7.6%), SP
dissolution failure averaged over 90%. The authors of the report conclude: These figures
suggest a significant problem of substandard products being found in most countries and
at all levels of the distribution chain.
Table 9.7 shows failure rates in quality tests for a mixed sample of tracer medicines in the
public, private and NGO sectors (where applicable) in five countries and one Indian state.
No quality failures occurred in private and NGO facilities in Tanzania, Ghana and
Rajasthan State (India). However, failure rates of up to 50% were found in El Salvadors
public sector and failure rates in excess of 10% were common.
TABLE 9.7
Public facilities
Private facilities
NGO
Brazil
Cambodia
El Salvador
Tanzania
Ghana
Rajasthan (India)
18.18% (n=22)
19.57% (n=46)
50% (n=30)
11.4% (n=35)
6.0% (n=50)
6.0% (n=50)
18.18% (n=22)
17.81% (n=73)
28.6% (n=35)
13.0% (n=35)
0.0% (n=33)
14.08 (n=71)
15.0% (n=20)
27.3% (n=22)
0.0% (n=7)
2.97% (n=101)
0.0% (n=4)
Quality of manufacturing
Studies in 10 countries show great variation in violations of GMP and in the sanctions
taken against violators. Reflecting capacity differences, the percentage of manufacturing
plants inspected varied between a low of 22% in Zimbabwe and 100% in Australia and
Cuba. Manufacturing plants in violation of GMP varied between a low of 1% (in Australia) and highs of 100% in Estonia and Venezuela. While no sanctions were imposed on
GMP violators in Australia and Cuba, there were more than 11 sanctions for 20 inspections and violations in Tunisia, and 78 sanctions for 40 inspections and 10 violations in
Venezuela.
TABLE 9.8
Australia
Cuba
Cyprus
Estonia
Malaysia
Netherlands
Tunisia
Uganda
Venezuela
Zimbabwe
Manufacturing
plants
322
26
9
6
105
86
23
9
41
23
Inspections
322
26
7
5
77
28
20
5
40
5
Violations in
GMP
(%)
3
4
1
5
6
3
1
3
10
1
1%
15%
14%
100%
8%
11%
5%
60%
25%
20%
Sanctions
3
4
5
11
6
78
3
101
BOX 9.3
In May 2002, the FDA announced that Schering-Ploughs Corporation had signed a
consent decree related to a permanent injunction. The company agreed to measures
assuring that the drug products manufactured at its New Jersey and Puerto Rico plants
are to be made in compliance with FDAs current good manufacturing practice (GMP)
regulations. Schering agreed to pay US$ 500,000,000 to the U.S.Treasury after the
consent decree has been entered by the court. The Government sought this money to
disgorge profits made by the company on drug products that were produced over the
last three years in violation of GMP regulations. The Governments action in this case
follows 13 inspections at four New Jersey and Puerto Rico facilities since 1998, during
which time the FDA found significant violations of the GMP regulations related to
facilities manufacturing, quality assurance, equipment, laboratories, and packaging and
labelling. As part of the decree, the company has agreed to suspend manufacture of 73
other products. To ensure that it stays in compliance with GMP requirements after entry
of the decree, the firm has agreed to submit comprehensive workplans for each facility
for FDA concurrence. Station-trained personnel at each facility will provide full-time
oversight of all operations at the facilities, and have their expert consultants conduct
yearly inspections of the facilities for a period of three years. For at least five years after
entry of the injunction, the company must conduct regular audits of its operations and
make reports to the FDA concerning its continuing compliance, and the FDA will
periodically inspect Schering Ploughs manufacturing operations to evaluate the
regulatory status of those operations [nytimes.com May 24, 2002].
9.4
TABLE 9.9
Low-income
Middle-income
High-income
Total
Law on promotion
Regulation of promotion
35 (55.6%)
54 (57.4%)
20 (57.1%)
25 (39.7%)
46 (48.9%)
18 (51.4%)
109 (56.8%)
89 (46.3%)
Results from the recent WHO study2 confirm the widespread existence of regulatory gaps
areas of pharmaceutical activity that fall outside the control of existing laws and
institutions. Many regulatory bodies fail to provide the tools, such as guidelines and
standards, needed to support effective regulation. Regulatory gaps also occur where laws
do apply but where the regulatory agency fails, for one reason or another, to implement
its mandate. A common and important area of neglect, for example, was found to be the
quality of medicines in the informal sector of the economy, which often accounts for a
very high proportion of retail sales.
102
MEDICINES REGULATION
Labelling
Pharmaceutical regulators in the USA and in a number of countries pay close attention to
the product labelling. As pharmaceutical products are likely to be distributed in a variety
of ways, some going out through informal channels, the labelling of drugs and the
package insert becomes important. Most drug products exported from the United States
are in bulk form and are repackaged and labelled elsewhere.21 A widely-quoted 1993 study
by the United States Office of Technology Assessment found that up to two thirds of
pharmaceuticals sold by US companies in developing countries were mislabelled.20 The
report found that warnings and precautions were underestimated, and clinical and
descriptive pharmacological information was lacking in many foreign labels.
If the regulatory authority considers a pharmaceutical to be a prescription-only item, it
may well be that the package insert provides only limited information, on the assumption
that the physician (or drug seller) will be instructing the user. In reality, this is often not
the case, since many drugs in developing countries can be obtained without a prescription
and patients often do not receive important information.20 The problem is exacerbated
where literacy is at a low level.
In addition, many regulatory agencies were found to devote excessive resources to premarketing assessments for registration purposes, and too little to the monitoring of
adverse reactions to registered products or their routine re-evaluation. Similarly, it
was found that regulators paid scant attention to the inspection and regulation of
national distribution systems and channels, and focused too much on the regulation of
manufacturers.
Post-marketing pharmacovigliance
Adverse drug reactions (ADRs) may not be detected until a drug is used after launch, in
part because animal toxicology studies are often poor predictors of human effects, the
sample size of the clinical trials are usually small, the duration of the clinical trials are
often short, and susceptible patients (e.g., those with concurrent disease or medications)
are often not included in trials.22 The main sources of information on the safety of drugs
in regular use can be from spontaneous reports, published case reports, so-called phase
IV procedures and controlled prospective or retrospective studies. Reliance on these
sources of reporting has been criticized as being inadequate.23 For many drugs, especially
those not widely used or in developing countries, there is virtually no post-marketing
safety monitoring.24,22 This is because comprehensive post-marketing surveillance is
constrained by many factors including: a general under-reporting because of lack of
knowledge of ADRs, fear of medical negligence or non-compliance; specific underreporting because of lack of patient follow-up; inability to measure cumulative toxicity
because of the lack of systematic records of repeated use; and lack of information on
populations at risk. In developing countries, other systemic factors that are relevant to
many DRAs come into play, such as difficulty in transmitting reports, lack of resources for
promotion of ADR reports, and difficulties in DRAs implementing policy decisions so
that health warnings are circulated in a limited way.25
In the WHO 10 country survey, only Uganda did not have a system for monitoring
ADRs.2 Each of the other nine countries uses a spontaneous reporting system for health
professionals. Reporting by the pharmaceutical industry is mandatory in most of the
countries.2 The launching of drugs in most developing countries often requires that the
sponsor monitor the patients for adverse reactions in collaboration with the national
government or DRA.23 However, the sponsor frequently has neither the time, money nor
103
infrastructure to do this adequately. The increase in access to the Internet and the general
trend towards globalization, in theory at least, support the idea that DRAs should create
globally standardized ADR reporting systems. Uniformity of data collection, processing,
evaluation and reporting can remove the potential for disputes and misunderstandings. In
addition, it eliminates duplication of effort throughout various DRAs.26
In the early 1970s, the WHO set up an international programme for adverse reaction
monitoring in order to identify rare adverse drug reactions that could not be found
through clinical trial programmes.27 This international database of ADR case reports has
expanded over time to accommodate the totality of drug safety monitoring. The international centre is called the WHO Collaborating Centre for International Drug Monitoring
and is located in Uppsala, Sweden (now known as the Uppsala Monitoring Centre
(UMC)). The Centre maintains the international database and serves various national
centres associated with WHO. National centres are appointed by the governments of each
of the countries participating in the WHO programme and they are responsible for
collecting spontaneous ADR reports originating from health professionals. At present,
national pharmacovigilance centres in 60 countries report adverse reactions to a central
database maintained by the Uppsala Monitoring Centre in Sweden. The database is large.
In 2001, it contained almost 2.5 million reports.28 Nevertheless, to find new adverse
reactions from combinations of drugs and also to identify previously unknown patterns
may require sophisticated data mining procedures.27 A recent WHO publication29
highlights the strengths and weaknesses of present pharmacovigilance systems.
9.5
104
in theory, only one set of guidelines need be set for all regions, and consequently the
amount of duplicative human and animal experimentation is reduced
improved and coordinated technical harmonization will give developing country DRAs
greater bargaining /negotiating power when dealing with outside DRAs, multinationals
and/or foreign manufacturers
the cost of development of new drugs can be reduced, which ought to lead to lower
prices; local products are more likely to be acceptable for export to other countries.
MEDICINES REGULATION
105
106
MEDICINES REGULATION
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2 Ratanwijitrasin S, Wondemagegnehu E. Effective drug regulation: a multicountry study. Geneva, World
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3 Agege C. Products and the consumer: an analysis of food and drug legislation in Nigeria. Food Drug and
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proposals for reform. Pretoria, Department of Health, South Africa, 1998.
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9 Regulatory situation of herbal medicines: a worldwide review. Geneva, World Health Organization, 1998.
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10 Guidelines for the assessment of herbal medicine programme. Geneva, World Health Organization, 1993.
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13 Petrovick PR, Marques LC, de Paula IC. New rules for phytopharmaceutical drug registration in Brazil.
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14 WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-third Report. Geneva,
World Health Organization, 1993. (WHO Technical Report Series, No. 834:130).
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16 Horton L. Pharmaceuticals and medical devices: international harmonization and mutual recognition
agreements. Seton Hall Law Review, 1998, 29:692.
17 Ollila E, Hemminki E. Secrecy in drug regulation: licensing documentation on the Norplant
contraceptive. International Journal of and Risk and Safety in Medicine, 1999, 9:16172.
18 Bruneton C, Naboulet P, van der Heide B, Rey JL. The drug trade between European countries and
developing countries. Med. Tropicale, Mar 1997, 57 (iv): 375379.
19 Quality assurance for TB Drugs. Issues paper prepared by Management Sciences for Health for the WHO/
Stop TB Global Drug Facility, 2001, (http://www.stoptb.org/gdf/drugsupply/MSH_QA_Paper_Final_
version4.pdf).
20 Maponga C, Ondari C. The quality of antimalarials. A study in selected Africa countries. Geneva, World Health
Organization, 2003.
21 Gelband H, Corrigan J, McDonough R. Methodology of OTAs report on drug labelling in developing
countries. International Journal of Technology Assessment in Health Care, 1993, 9 (ii):238250.
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22 Edwards IR. Who cares about pharmacovigilance? European Journal of Clinical Pharmacology, 1997,
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23 Edwards IR. Safety monitoring of new anti-malarials in immediate post-marketing phase. Med. Tropicale,
1998, 58: 93S96S.
24 Lindquist M, Edwards IR. The WHO programme for international drug monitoring, its database, and the
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26 Peachey J. From pharmacovigilance to pharmacoperformance. European Pharmaceutical Review, 2000, 5(ii).
27 Olsson S. The role of the WHO Programme on International Drug Monitoring in coordinating
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28 Coulter D, Moulter D, Bate A, Meyboom R, Lindquist E, Edwards IR. Antipsychotic drugs and heart
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29 The importance of pharmacovigilance. Geneva, World Health Organization, 2002.
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108
CONCLUSION
CONCLUSION
In the 15-year interval since the publication of the first review of the world pharmaceutical situation (The World Drug Situation) there has been both progress and failure. Almost
2 billion people today still lack access to essential medicines. While this is a smaller
percentage of the global population than in 1985, when the first survey was carried out,
gross inequity in access to medicines remains the overriding feature of the world
pharmaceutical situation.
One encouraging finding is that many more countries now have national policies on
medicines than in 1985. However, in low-income countries, all too often these policies
lack implementation plans and supporting strategies, such as price regulation, generic
promotion or the effective regulation of quality.
Meanwhile, over the past 15 years there has been a notable change in the global context in
which national medicines policies are being implemented. Nothing illustrates this more
clearly than the tragedy of the HIV/AIDS epidemic. The global burden of disease has
undergone a major shift, as the scale and impact of HIV/AIDS has become fully apparent.
In 1988, there were an estimated 6.3 million HIV/AIDS cases worldwide. By the end of
2002, an estimated 42 million people were living with HIV/AIDS and in that year alone
3.1 million people died of AIDS. The global response to the HIV/AIDS pandemic has
brought to the fore a number of key issues in medicines policy. Firstly, it has confirmed
the importance of innovation. The R&D of new, safe and effective medicines is critical in
saving lives and reducing suffering from a new disease on an epidemic scale.i However,
many of these medicines have been at the centre of continuing controversies about prices
and the legal limits to competition through intellectual property rights in the form of
patents. Patents have unusual importance in medicines policy.1 A major shift towards
the development of a global trading system with a single set of rules has occurred since The
World Drug Situation was published. Intellectual property rights occupy an important place
in this system, and medicines have held centre stage in arguments in and around the
World Trade Organization about whether, and at what speed, to implement a single set
of international trade rules.
The high price of new medicines for HIV/AIDS in relation to their production cost has
reopened interest in competition. Brazil began supplying its domestic market with generic
HIV/AIDS drugs and Indian manufacturers of generic HIV/AIDS medicines entered into
the markets of sub-Saharan Africa. Meanwhile, the authority of national governments to
regulate their national medicines market by invoking compulsory licensing arrangements
has been both asserted and challenged over medicines for HIV/AIDS.
The high price of medicines for HIV/AIDS has also highlighted the importance of riskpooling mechanisms that can ensure access to treatment on the basis of medical need
rather than ability to pay. This reinforces the importance of financing medicines through
government revenues, health insurance, or a mix of both. Brazils social security system
Antiretroviral medicines went on the WHO Model List of Essential Medicines for the first time in 2002.
109
and numerous employers, including several large firms in South Africa, offer examples
of middle-income countries where access to treatment has been made possible through
health insurance schemes.
Finally, the human and physical capacity limits of health systems in many low-income
countries have been brought into sharp focus as they attempt to deal on a national scale
with prevention and counselling, and to provide treatment and care for those living with
HIV/AIDS.
Elsewhere, the overall production of medicines has undergone important changes over
the past 15 years, as the number of pharmaceutical manufacturers has fallen and market
share has increased. In 1987, the largest single manufacturer had a 3.4% share of global
sales. By 2000, the largest manufacturer had a 7.3% share of the global market, and the top
10 manufacturers 45.7%.i This concentration is the result of more than 30 mergers among
major manufacturing companies that occurred between 1988 and 1999.ii
Today, following a period of record profitability in the late 1990s, manufacturers are
attempting both to improve their product pipeline and rationalize the high fixed costs of
R&D and marketing. There have been substantial changes in both the process and content
of R&D, following the development of the biotechnology industry and its concentration
in small specialist firms. Another development is the emergence of very large generic
medicine production markets in India and China, consisting of thousands of small
manufacturers and a small number of very big enterprises. By 1999, India had become the
worlds tenth largest net exporter of pharmaceuticals.
Overall, the dominant picture that emerges from our analysis is of extreme and worsening
disparity. As documented in the 1988 report, the pharmaceutical situation is one of
extraordinary, and sometimes growing, asymmetries: in production, trade, consumption,
and in peoples access to the medicines they need. A small number of countries and
companies dominate the global market and the best market opportunities are provided by
the lifestyle-related illnesses of the affluent. At the same time, the needs of almost two
billion people in the lowest income groups remain unmet.
IMS data based on audit of 59 countries plus estimates of the remainder, cited in Pharmaceuticals Global Insights
presentation by John Morris of KPMG, February 2002.
ii
REFERENCE
1 Scherer FM. The pharmaceutical industry. In: Handbook of health economics, vol.1. Culyer AJ,
Newhouse JP, eds. Amsterdam, Elsevier BV, 2000.
110
WORLD MEDICINE
STATISTICAL
PRODUCTION
ANNEX
111
112
STATISTICAL ANNEX
STATISTICAL ANNEX
Annex Table 1
Production, trade, sales
Annex Table 2
Expenditure
Annex Table 3
1999 World drug survey access, national medicines policies
Annex Table 4
1999 World drug survey quality control, essential medicines lists, procurement
113
Region
Afghanistan
Albania
Algeria
Andorra
Angola
EMRO
EURO
AFRO
EURO
AFRO
Inc level
DALE
168
102
84
10
165
AMRO
AMRO
EURO
WPRO
EURO
2
2
1
3
3
48
39
41
2
17
Azerbaijan
Bahamas
Bahrain
Bangladesh
Barbados
EURO
AMRO
EMRO
SEARO
AMRO
1
3
2
1
2
65
109
61
140
53
Belarus
Belgium
Belize
Benin
Bhutan
EURO
EURO
AMRO
AFRO
SEARO
2
3
2
1
1
83
16
94
157
138
Bolivia
Bosnia and Herzegovina
Botswana
Brazil
Brunei Darussalam
AMRO
EURO
AFRO
AMRO
WPRO
2
2
2
3
133
56
187
111
59
Bulgaria
Burkina Faso
Burundi
Cambodia
Cameroon
EURO
AFRO
AFRO
WPRO
AFRO
2
1
1
1
1
60
178
179
148
156
Canada
Cape Verde
Central African Republic
Central America
Chad
AMRO
AFRO
AFRO
3
2
1
12
118
175
AFRO
161
Chile
China
Colombia
Comoros
Congo
AMRO
WPRO
AMRO
AFRO
AFRO
2
1
2
1
1
32
81
74
146
150
Cook Islands
Costa Rica
Cte dIvoire
Croatia
Cuba
WPRO
AMRO
AFRO
EURO
AMRO
2
1
2
2
67
40
155
38
33
Cyprus
Czech Republic
Democratic Peoples Republic of Korea
Democratic Republic of the Congo
Denmark
EMRO
EURO
SEARO
AFRO
EURO
3
2
1
3
25
35
137
174
28
Djibouti
Dominica
Dominican Republic
Ecuador
Egypt
EMRO
AMRO
AMRO
AMRO
EMRO
2
2
2
2
2
166
26
79
93
115
114
2
2
Production
Imports
1985
1991
1997
1985
1991
1997
1985
US$000
US$000
US$000
US$000
US$000
US$000
US$000
218887
217287
11567
373379
64
23918
797547
540854
100519
1693463
1634564
212973
2261537
2352284
320541
2656000
103406
182540
241766
338437
727671
1014271
11501
10984
28068
11231
19914
37290
16852
546585
2789
1767455
663596
43751
1642104
1913743
20438
82725
252512
19453
30656
92188
24785
23
197
3623509
4871
23231
662445
160
1329
24049
12433
18591
26515
120232
6730
425829
14010
1461421
27426
61480
93618
53177
2050561
4067311
5561960
424535
1010655
2259765
4137
165048
413884
106419
547631
633444
214025
1209985
30987
77574
520372
70185
232511
330757
400942
1638
48904
471819
73645
21267
54694
58485
75207
44735
58938
20440
19
66146
119639
25637
966
185122
5549
27018
54945
50284
80508
694135
6115
551958
835047
451988
5872
1117
1769
131366
155494
206868
315199
20229
570000
40471
873599
1618552
76532
464108
4595983
27187
221000
128760
1237811
4429
674
39089
56274
88843
1534
2816
4693
STATISTICAL ANNEX
Total sales*
1991
1997
US$000
US$
34
329
57299
1990
Licensed
Brands
2000
Original
Brands
Other
Brands
Patent
N/A
107582
270532
780626
147814
65442
133204
519557
353219
439861
298992
Unbranded
Licensed
Brands
Original
Brands
Other
Brands
Patent
N/A
Unbranded
49547
307881
802472
1901959
307815
105620
109028
134907
6908
58981
339734
316309
1318686
749349
708676
381394
133382
113385
17766
67652
3943
229177
781188
284437
1090
678135
1324880
332
343
5557
240
4327
7358
15014
67950
23453
4675
10658
27460
201359
46151
4053
1911686
4885516
163245
833697
417308
165962
36595
391550
1330255
510930
148551
42402
217489
781237
1273883
413132
81158
505088
1630017
2287858
571517
164758
306098
1400589
1377406
357296
158030
989770
2895646
1379043
349923
549049
8419
46439
95586
34975
8662
42685
140569
243516
62105
36387
7409
35639
83004
27465
27296
29479
114601
288792
65468
51285
31182
281416
202240
110437
21120
62425
217779
340347
101289
74405
19328
15054
107817
43818
36031
67073
226688
262644
56275
46922
2493
14631
48719
12316
4790
12481
50032
137264
27550
16096
61346
83220
175583
57094
16957
128244
165203
351362
100928
24661
98
19
229
99710
217291
150
137113
303
254340
964549
11
15282
773787
20476
31148
1536246
175066
35984
69928
156594
23128
1200325
38543
213736
2272449
2920
20715
1
1945
25096
55604
115
Region
Inc level
DALE
Production
Imports
1985
1991
1997
1985
1991
1997
1985
US$000
US$000
US$000
US$000
US$000
US$000
US$000
El Salvador
Equatorial Guinea
Eritrea
Estonia
Ethiopia
AMRO
AFRO
AFRO
EURO
AFRO
2
2
1
2
1
87
152
169
69
182
Fiji
Finland
France
French West Africa
Gabon
WPRO
EURO
EURO
2
3
3
106
20
3
AFRO
144
Gambia
Georgia
Germany
Ghana
Greece
AFRO
EURO
EURO
AFRO
EURO
1
2
3
1
3
143
44
22
149
7
Grenada
Guatemala
Guinea
Guinea-Bissau
Guyana
AMRO
AMRO
AFRO
AFRO
AMRO
2
2
1
1
2
49
129
167
170
98
Haiti
Honduras
Hungary
Iceland
India
AMRO
AMRO
EURO
EURO
SEARO
1
1
2
3
1
153
92
62
19
134
Indonesia
Iran, Islamic Republic of
Iraq
Ireland
Israel
SEARO
EMRO
EMRO
EURO
EURO
1
2
2
3
3
103
96
126
27
23
Italy
Jamaica
Japan
Jordan
Kazakhstan
EURO
AMRO
WPRO
EMRO
EURO
3
2
3
2
2
6
36
1
101
122
4011000
4450230
4937558
15972432
39775216
74339
56768000
Kenya
Kiribati
Kuwait
Kyrgyzstan
Lao Peoples Democratic Republic
AFRO
WPRO
EMRO
EURO
WPRO
162
125
68
123
147
Latvia
Lebanon
Lesotho
Liberia
Libyan Arab Jamahiriya
EURO
EMRO
AFRO
AFRO
EMRO
82
95
171
181
107
Lithuania
Luxembourg
Madagascar
Malawi
Malaysia
EURO
EURO
AFRO
AFRO
WPRO
2
3
1
1
2
63
18
172
189
89
Maldives
Mali
Malta
Marshall Islands
Mauritania
SEARO
AFRO
EURO
WPRO
AFRO
2
1
3
130
183
21
121
158
116
3
1
1
2
2
1
118200
61003
45978
115171
14550
70263
17141
227980
6022557
578391
14998263
652663
22517920
4930
148941
787038
8911
445117
3084597
618586
5875385
7
63287
1536065
4727
6623913
17870548
23087608
252476
672868
1793245
273817
130808
112534
4226912
7117795
122810
387016
984078
36528
1414
45576
1971
63591
2891
124565
15040
47466
1388
18821
17484
2116391
3312667
497705
992013
26837
50748
227243
31505
227729
76058
485755
47807
388862
1624
349415
6012453
55916
144839
12392
146202
1314302
83097
138586
262638
393045
15400
178532
59461
503605
201609
897235
486678
198163
20934
966903
11316
1291884
42887
3029695
22951
3114112
58465
4763626
60392
4243178
64485
59222
859591
2640
391051
36339
28410
238
56040
390
21569
95651
5351
129697
169845
98418
38699
83842
106664
180610
7527
55456
96143
177699
7947
5344
118110
9121
9995
12264
193868
23838
23717
370132
5
100
17798
25375
3585
18011
47895
3486
STATISTICAL ANNEX
Total sales*
1991
1997
US$000
US$
14529
1990
2000
Licensed
Brands
Original
Brands
Other
Brands
Patent
N/A
Unbranded
Licensed
Brands
Original
Brands
Other
Brands
Patent
N/A
Unbranded
63922
1432934
17568
222499
4918394
65763
307133
3470982
113511
66907
1798168
73024
13874
217160
9966
119036
2811085
10737
468018
7665118
61054
322216
3872697
86689
51904
1835293
42465
24916
503023
6927
53111
31773
116
18
139368
3955696
214488
7900846
27
6575126
11654976
1307245
3555786
4779724
1633470
670638
1990510
5648584
5721883
1728055
1139085
70663
89493
41319
290077
223378
38528
5746
188165
598055
292521
38982
4427
61857
68540
1219
1291
357260
5861
947204
42757
51587
125922
41668
14146
115082
325088
243651
57290
34683
227
483471
21638
41357
2267
16706
96219
221617
57863
14101
28413
149655
315352
72109
29173
1150583
95745
3356685
416716
15474
6604
101890
27421
68955
65061
13818
18289
3353
1521
78066
28517
227474
109657
130934
124741
17216
18500
5525
2143
1629241
2996
1089475
50633
4430346
828
1952405
21362
5176
1953233
3228248
4017128
1150457
383122
2692809
4484176
2879652
709474
169767
5318803
9409592
8096757
2223624
1222166
10946413
20969289
14474656
3648654
1423052
8949
30740
53
685
3313
25319
17637
5869
607
10452
52030
21345
5489
924
2958
29155
34971
10370
2521
14503
97429
69185
23959
5994
47276
67265
1
111
43829
3
72287
9235
215
24246
117
Region
Inc level
DALE
Mauritius
Mexico
Micronesia, Federated States of
Monaco
Mongolia
AFRO
AMRO
WPRO
EURO
WPRO
2
2
Morocco
Mozambique
Myanmar
Namibia
Nauru
EMRO
AFRO
SEARO
AFRO
WPRO
2
1
1
2
110
180
139
177
136
Nepal
Netherlands
New Zealand
Nicaragua
Niger
SEARO
EURO
WPRO
AMRO
AFRO
1
3
3
1
1
142
13
31
117
190
Nigeria
Niue
Norway
Oman
Pakistan
AFRO
WPRO
EURO
EMRO
EMRO
1
3
2
1
163
85
15
72
124
Palau
Panama
Papua New Guinea
Paraguay
Peru
WPRO
AMRO
WPRO
AMRO
AMRO
2
2
2
2
112
47
145
71
105
Philippines
Poland
Portugal
Qatar
Republic of Korea
WPRO
EURO
EURO
EMRO
WPRO
2
2
3
3
2
113
45
29
66
51
Republic of Moldova
Romania
Russian Federation
Rwanda
Saint Kitts and Nevis
EURO
EURO
EURO
AFRO
AMRO
1
2
2
1
2
88
80
91
185
86
Saint Lucia
Saint Vincent and the Grenadines
Samoa
San Marino
So Tom and Principe
AMRO
AMRO
WPRO
EURO
AFRO
2
2
2
1
54
43
97
11
132
Saudi Arabia
Senegal
Seychelles
Sierra Leone
Singapore
EMRO
AFRO
AFRO
AFRO
WPRO
2
1
2
1
3
58
151
108
191
30
Slovakia
Slovenia
Solomon Islands
Somalia
South Africa
EURO
EURO
WPRO
EMRO
AFRO
2
3
1
2
42
34
127
173
160
Spain
Sri Lanka
Sudan
Suriname
Swaziland
EURO
SEARO
EMRO
AMRO
AFRO
3
2
1
2
2
5
76
154
77
164
118
78
55
104
9
131
Production
Imports
1985
1991
1997
1985
1991
1997
1985
US$000
US$000
US$000
US$000
US$000
US$000
US$000
1463
1070000
2064
1783514
3006
2972824
6321
130064
21660
346270
31095
898716
36669
261149
32587
85101
136471
5003
5
609201
23632
563
1001686
95000
21456
24632
129425
5744
2648596
3536068
483793
155399
455812
1336975
311866
595313
711129
16837
18234
20383
172364
404747
425144
353678
724527
1146765
192357
687843
2459635
1380198
3636616
4814558
24187
18733
579921
110915
52872
25175
1540705
258646
40132
45422
3478147
417075
75203
9489
187274
3
145853
24775
134353
71106
123258
432658
41506
207286
618804
62044
265335
43246
97
2523
50390
9188
7160
38882
64982
113085
24486
63789
59194
179516
4103
3
5
2395
54450
255442
124780
10790
113211
148048
435776
341109
23152
352742
350559
1311086
699953
6727
233708
46763
724741
42207
55468
44106
181179
1768492
1613
1482
2227
365011
37355
1096
622688
44416
2319
108677
219181
722278
16927
230342
832956
3012111
121349
3816
1905
135
135717
347933
187582
890
413700
1125915
1943961
1837172
6712343
9399
16038176
244642
22328
22542
1175290
38855
8489
2746540
48239
7339
233103
291
STATISTICAL ANNEX
Total sales*
1991
1997
1990
2000
US$000
US$
Licensed
Brands
Original
Brands
Other
Brands
Patent
N/A
1697
128346
929
636834
105272
491553
603353
164245
17322
9397
36047
32410
76792
21
3770552
54969
1182
12
18627
154862
32003
44524
Unbranded
Licensed
Brands
Original
Brands
Other
Brands
Patent
N/A
Unbranded
30553
505459
1880508
1929867
544840
43595
33464
4213
76344
85576
171772
45849
6386
83754
25190
7754
35062
222798
109185
27384
14047
206625
125947
39480
16984
87077
480915
162293
35849
23799
143400
162417
71652
23236
63039
205917
361070
70324
14187
662
1513097
40946
292
157
140838
69
14520
217871
1996
32104
7143
1
453
4196
14045
14697
60364
99088
30428
2874
17069
68514
134678
29837
18558
9444
322468
89443
31044
294560
171707
36380
136223
258787
60777
9467
98000
400138
489505
104094
25883
83491
332247
288810
67161
4105
236131
679797
515540
81574
9547
139363
289844
196047
182208
1293735
312651
195542
386885
598777
1603405
335107
272616
13181
3495
30850
116472
22252
158762
141255
39791
3443
79361
291129
261901
48758
4853
3770
22523
10
7227
346
1547
220652
616571
2451
22529
18330
6212
2628
19109
100454
47324
14039
5851
145649
402036
13908
6553
60149
26431
23992
38825
122572
119242
30792
19727
43018
212922
232491
56283
7708
79143
330594
320687
61790
17255
529465
1031739
1481231
309273
90861
1556136
2876284
1909587
448197
302162
737529
785
1516932
119
Region
Inc level
DALE
Production
1985
1991
1997
1985
1991
1997
1985
US$000
US$000
US$000
US$000
US$000
US$000
US$000
646217
2409411
4391386
332181
493288
133459
805130
1357707
1230853
3517053
23706
405469
1603645
136
110335
238667
511711
10080
21017
1056
41164
136400
288834
Sweden
Switzerland
Syrian Arab Republic
Tajikistan
Thailand
EURO
EURO
EMRO
EURO
SEARO
3
3
2
1
2
4
8
114
120
99
EURO
AFRO
WPRO
AMRO
EMRO
2
1
64
159
75
57
90
Turkey
Turkmenistan
Tuvalu
Uganda
Ukraine
EURO
EURO
WPRO
AFRO
EURO
2
1
1
2
73
128
119
186
70
EMRO
EURO
AFRO
AMRO
AMRO
3
3
1
3
2
50
14
176
24
37
Uzbekistan
Vanuatu
Venezuela, Bolivarian Republic of
Viet Nam
Yemen
EURO
WPRO
AMRO
WPRO
EMRO
2
2
2
1
1
100
135
52
116
141
AFRO
AFRO
1
1
46
188
184
30335
163220
*6/2/03
*6/2/03
*6/2/03
*7/2/03
*7/2/03
2
2
Zambia
Zimbabwe
120
Imports
740297
446566
4428
33282
75684
695
322265
53250
1716517
2160366
76711
25
41531
15105
37021
168332
278
1092
811079
15570
22
15952
51250
760807
99349
2422256
5194598
4377
1846018
97505440
1717992
15712
3092086
37807
8819067
111934
2790444
3288
457554
104902
116685
247036
2556
5184499
13278308
23326532
31500000
108249
60840000
415467
436003
8256
78449
12917
*7/2/03
24751
48380
3845
STATISTICAL ANNEX
Total sales*
1991
1997
US$000
US$
1724648
4658423
34234
1990
2000
Licensed
Brands
Original
Brands
Other
Brands
Patent
N/A
3057619
8208497
7342
75901
493796
405571
160514
106551
10367
86519
183503
70523
Unbranded
Licensed
Brands
Original
Brands
Other
Brands
Patent
N/A
Unbranded
23129
236853
903457
433505
149020
36519
31759
33663
232525
301058
81722
46115
18818
25
1942
4501
2163
14561
5099
26230
36534
17925
2901
16885
59198
67850
20696
3166
53498
113568
113835
128675
342895
80114
16241
420732
726703
1009636
136315
27718
421
4515065
8940218
947
410344
9011
2495569
11300
1370253
3648
470506
171
467107
6046
1291394
45851
5349022
38199
2434297
10315
653919
777
1402711
4608533
14552
8036944
22572
5212904
2257
11453723
7522
9902688
26129
2291962
9826
1928474
3142
22761819
8464
60951686
26347
17895806
85080
4844184
23051
6776252
7314
7322
48304
16271
92904
128790
46170
10046
98668
416918
471275
145229
94757
65408
2849
5693
* IMS Health & Area Classifications
121
Total expenditure on
health (per capita at
average exchange rate)
Total expenditure on
pharmaceuticals (% total
expenditure on health)
Total expenditure on
pharmaceuticals (per
capita at exchange rate)
1995
2000
1995
2000
1995
2000
Afghanistan
Albania
Algeria
Andorra
Angola
13
27
73
1282
17
9
46
68
1200
25
9.6
15.1
23.8
5.4
19.7
15
16.5
21.3
7.6
20.3
1
4
17
70
3
1
8
15
92
5
415
620
23
1700
2498
509
683
22
1808
1873
31.5
26.7
61.7
11.2
13.3
26.9
28.9
52.6
13.5
17.3
130
165
14
191
331
137
198
12
245
323
19
587
455
10
451
31
863
483
14
603
7.7
13.8
15
53.3
19.2
7.8
13.4
15.3
37.9
24.7
1
81
68
5
87
2
115
74
5
149
56
2407
137
13
5
61
1916
156
15
9
11.2
16.0
18.4
22.5
48.8
11.9
16.4
20.9
15.2
26.2
6
386
25
3
2
7
315
33
2
2
39
37
170
316
458
52
87
173
265
469
24.2
n/a
23.2
16.8
22.3
24.1
n/a
26.3
23.2
23.3
10
n/a
39
53
102
13
n/a
45
61
109
69
7
7
20
27
75
6
5
30
19
23.9
53.1
32.1
37.9
32
22
44.1
29.8
36.7
44.5
16
4
2
7
9
16
3
2
11
9
1818
40
12
2102
56
12
13.7
54.7
28
14.9
32.4
32.6
248
22
3
313
18
4
Azerbaijan
Bahamas
Bahrain
Bangladesh
Barbados
Belarus
Belgium
Belize
Benin
Bhutan
Bolivia
Bosnia and Herzegovina
Botswana
Brazil
Brunei Darussalam
Bulgaria
Burkina Faso
Burundi
Cambodia
Cameroon
Canada
Cape Verde
Central African Republic
Central America
Chad
27.8
38.3
Chile
China
Colombia
Comoros
Congo
307
22
158
12
19
328
45
108
9
18
10.7
51.7
11.5
44.8
79.9
14.2
45.1
17.4
53.7
46.7
33
11
18
5
15
46
20
19
5
9
Cook Islands
Costa Rica
Cte dIvoire
Croatia
Cuba
288
230
44
363
122
196
280
42
388
175
18.3
15.5
18.9
18.1
27.8
25.6
14.9
17.5
18.3
25.9
53
36
8
66
34
50
42
7
71
45
860
367
8
4
2826
904
358
21
10
2474
24.1
25.6
n/a
6.8
9.1
32.1
22
n/a
19.9
8.7
208
94
n/a
290
79
n/a
256
215
60
173
100
73
36
58
200
145
52
52
34.6
20
15.6
24.1
43.9
22.9
28.5
16.1
25.6
40.3
21
35
16
18
16
13
57
23
13
21
Cyprus
Czech Republic
Democratic Peoples Republic of Korea
Democratic Republic of the Congo
Denmark
Djibouti
Dominica
Dominican Republic
Ecuador
Egypt
122
STATISTICAL ANNEX
Government expenditure
on pharmaceuticals (per
capita at exchange rate)
Private expenditure on
pharmaceuticals (per
capita at exchange rate)
Private expenditure
as % total health
spending
1995
2000
1995
2000
3
12
53
4
11
70
1
1
1
5
16
3
1
4
4
22
4
47.4
28.5
20.2
13.4
52.1
94
39
3
103
212
96
41
5
133
227
36
127
4
88
120
41
157
13
112
97
37.1
44.8
58.5
30.7
28.6
29
1
43
28
1
46
1
56
42
5
58
2
73
46
5
103
26.6
46.3
28.7
65.3
39.8
6
166
6
1
2
6
157
6
1
2
1
220
19
1
1
157
27
1
12.8
29.0
47.1
51.5
9.6
2
n/a
22
4
95
3
n/a
23
5
100
7
n/a
18
49
7
10
n/a
23
57
9
36.1
44.6
29.5
59.7
59.4
9
2
1
2
13
2
1
1
1
7
1
1
7
7
4
1
1
10
7
20.0
32.4
57.8
90.6
70.6
81
13
1
113
12
2
167
8
2
200
7
2
30.1
28.2
48.6
n/a
n/a
n/a
20.7
5
4
5
n/a
n/a
10
6
6
n/a
n/a
28
8
13
n/a
n/a
37
14
13
n/a
n/a
62.1
60.6
42.4
31.8
35.4
n/a
13
1
56
14
n/a
17
1
61
21
n/a
23
7
9
20
n/a
25
6
10
24
32.9
21.7
54.0
19.5
12.5
68
79
n/a
n/a
124
82
73
n/a
n/a
106
139
15
n/a
n/a
132
208
18
n/a
n/a
109
63.7
8.3
16.5
25.9
17.7
13
24
3
6
3
6
37
5
3
3
8
10
12
12
12
8
20
18
10
17
55.6
30.4
70.9
49.2
68.2
25
26
123
Total expenditure on
health (per capita at
average exchange rate)
Total expenditure on
pharmaceuticals (% total
expenditure on health)
Total expenditure on
pharmaceuticals (per
capita at exchange rate)
1995
2000
1995
2000
1995
2000
El Salvador
Equatorial Guinea
Eritrea
Estonia
Ethiopia
107
19
8
153
3
169
56
9
222
3
28.6
14.6
38.4
24
53.5
26.6
12.4
38.8
22.3
39.4
31
3
2
37
2
45
7
4
49
1
Fiji
Finland
France
French West Africa
Gabon
98
1906
2555
80
1550
2067
11.4
14.1
17.6
15.6
15.5
20.4
11
268
450
12
240
421
93
130
43.7
25.5
41
33
Gambia
Georgia
Germany
Ghana
Greece
23
12
3101
16
1082
20
20
2408
11
1018
20.1
37.5
12.7
28.2
15.7
16.3
39.1
13.6
32.8
13.3
5
4
405
5
170
3
8
328
4
136
146
54
17
19
39
245
79
13
10
48
24.3
38
18.1
78.3
24.8
20.9
31.8
21.3
70.5
20.4
36
21
3
5
10
51
25
3
3
10
Haiti
Honduras
Hungary
Iceland
India
16
38
323
2149
21
22
54
305
2794
23
18.4
43.4
25
15.5
13.5
12.5
42.1
24.9
14.7
14.5
3
16
81
333
3
3
23
76
412
3
Indonesia
Iran, Islamic Republic of
Iraq
Ireland
Israel
24
98
147
1254
1596
20
312
214
1579
1612
18.5
15.7
n/a
10.4
9.3
26.7
12.6
n/a
10.6
10.7
4
15
n/a
131
149
5
39
n/a
168
173
Italy
Jamaica
Japan
Jordan
Kazakhstan
1415
96
2857
115
57
1512
173
2890
154
62
20.9
29.9
22.4
52.4
5.7
22.2
24.8
18.3
34.5
8.4
296
29
641
60
3
336
43
528
53
5
Kenya
Kiribati
Kuwait
Kyrgyzstan
Lao Peoples Democratic Republic
25
53
611
16
10
30
45
553
12
9
27.4
11.3
23
20.7
16.4
22.9
12.5
27.5
39.9
20.4
7
6
140
3
2
7
6
152
5
2
Latvia
Lebanon
Lesotho
Liberia
Libyan Arab Jamahiriya
119
384
30
32
163
191
607
29
2
175
22.4
27.5
13
24.7
17.6
39.8
21.2
12.1
21.4
17.8
26
106
4
8
29
76
128
4
1
31
98
2810
6
12
113
197
2442
6
12
129
29.2
12
24.8
21.4
12.4
20
12.1
24.7
21.7
11.2
29
338
1
3
14
39
295
1
3
15
64
10
713
213
16
104
10
811
188
13
21.8
35.2
17.4
16.2
33.1
19.7
28.4
21.8
16
29.6
14
4
124
35
5
20
3
177
30
4
Grenada
Guatemala
Guinea
Guinea-Bissau
Guyana
Lithuania
Luxembourg
Madagascar
Malawi
Malaysia
Maldives
Mali
Malta
Marshall Islands
Mauritania
124
STATISTICAL ANNEX
Government expenditure
on pharmaceuticals (per
capita at exchange rate)
Private expenditure on
pharmaceuticals (per
capita at exchange rate)
Private expenditure
as % total health
spending
1995
2000
1995
2000
3
1
1
26
1
6
3
2
22
1
27
1
1
10
1
39
4
2
28
1
61.3
44.0
34.2
11.5
58.6
5
121
276
5
121
273
6
147
174
7
120
148
33.3
23.9
23.9
38
21
33.5
n/a
1
272
n/a
121
n/a
1
227
n/a
100
n/a
4
127
n/a
50
n/a
6
102
n/a
36
21.3
91.4
23.4
44.9
44.8
10
3
n/a
n/a
6
15
5
n/a
n/a
6
26
17
3
n/a
3
36
20
2
n/a
3
34.3
55.1
42.8
36.0
18.5
3
54
224
1
5
57
265
1
3
13
27
109
2
2
18
19
147
2
66.5
44.6
24.7
16.3
84.7
1
8
n/a
101
22
20
n/a
134
26
4
7
n/a
30
127
5
19
n/a
34
147
76.2
53.6
41.1
24.4
31.9
113
2
438
15
2
149
4
348
14
3
183
26
203
45
1
187
39
180
39
2
27.8
46.5
20.5
37.4
23.6
1
6
119
1
5
116
1
6
n/a
22
2
2
6
n/a
36
4
2
71.8
0.9
12.6
30.6
63.2
12
6
n/a
n/a
n/a
26
8
n/a
n/a
n/a
14
99
n/a
n/a
n/a
50
121
n/a
n/a
n/a
39.4
79.4
24.0
33.3
52.4
14
276
22
241
17
54
1
2
11
26.1
7.5
42.8
49.4
42.4
10
1
71
n/a
1
25.5
54.2
29.1
38.1
30.3
1
4
15
62
1
2
10
8
2
75
n/a
n/a
11
2
106
n/a
n/a
6
1
49
n/a
1
125
Total expenditure on
health (per capita at
average exchange rate)
Total expenditure on
pharmaceuticals (% total
expenditure on health)
Total expenditure on
pharmaceuticals (per
capita at exchange rate)
1995
2000
1995
2000
1995
2000
111
182
149
1895
22
127
327
140
1610
23
39.1
21.1
n/a
n/a
15.7
35.5
24.9
n/a
n/a
15
43
39
n/a
n/a
3
45
8
n/a
n/a
3
Morocco
Mozambique
Myanmar
Namibia
Nauru
54
8
52
136
416
54
12
164
126
643
41.1
23.1
16.7
16.4
n/a
36.2
18.6
16
15.1
n/a
22
2
9
22
n/a
20
2
26
19
n/a
Nepal
Netherlands
New Zealand
Nicaragua
Niger
10
2253
1195
50
7
12
2003
1054
55
6
28.9
11
14.8
34.1
16.2
29.9
10.1
12.3
46.5
17.1
3
247
177
17
1
4
202
129
26
1
Nigeria
Niue
Norway
Oman
Pakistan
7
326
2689
230
21
13
290
2817
227
18
23.7
n/a
9.1
14.7
28.2
18.2
n/a
9.6
15
27.1
2
n/a
245
34
6
2
n/a
272
34
5
Palau
Panama
Papua New Guinea
Paraguay
Peru
429
231
30
130
101
454
260
27
112
96
n/a
11.1
31.1
27.3
29.5
n/a
15
34.3
38.9
24.2
n/a
26
9
35
30
n/a
39
9
44
23
Philippines
Poland
Portugal
Qatar
Republic of Korea
37
198
892
738
507
34
244
934
860
577
46
27.6
23.2
16.5
21.9
43.5
25
23.1
13.9
15.9
17
54
207
122
111
15
61
216
120
92
Republic of Moldova
Romania
Russian Federation
Rwanda
Saint Kitts and Nevis
28
55
126
12
255
18
104
95
13
364
8.3
17.9
14.1
26.9
15
12.2
23.3
17.8
21.3
16.4
2
10
18
3
38
1
25
12
3
60
150
134
60
1127
1
195
170
80
1196
7
12.2
26.7
13.9
22.1
20
16.1
23.7
13.7
28.8
16.1
27
36
8
249
11
36
40
11
338
8
Saudi Arabia
Senegal
Seychelles
Sierra Leone
Singapore
356
25
418
6
879
376
22
444
6
826
22.5
26.4
23.5
30.5
32.4
19.9
30
22.5
29
34.2
80
7
98
2
285
75
7
100
2
282
Slovakia
Slovenia
Solomon Islands
Somalia
South Africa
239
737
38
4
311
208
765
39
6
253
23.7
18.9
13.9
26.1
14.1
34
17.6
8.8
26.5
12.3
57
140
5
1
44
71
135
3
2
31
1133
24
13
119
45
1048
32
13
186
46
18
27
21.1
11.4
34.9
17.7
25
29.9
17.1
27.4
204
7
3
14
16
186
1
4
32
13
Mauritius
Mexico
Micronesia, Federated States of
Monaco
Mongolia
Saint Lucia
Saint Vincent and the Grenadines
Samoa
San Marino
So Tom and Principe
Spain
Sri Lanka
Sudan
Suriname
Swaziland
126
STATISTICAL ANNEX
Government expenditure
on pharmaceuticals (per
capita at exchange rate)
Private expenditure on
pharmaceuticals (per
capita at exchange rate)
Private expenditure
as % total health
spending
1995
2000
1995
2000
13
9
n/a
n/a
2
11
19
n/a
n/a
2
31
29
n/a
n/a
1
34
62
n/a
n/a
1
48.9
56.4
43.3
50.0
37.3
2
1
1
2
n/a
2
1
1
5
n/a
20
1
8
20
n/a
18
1
25
14
n/a
71.4
43.8
79.7
45.7
2.6
1
220
124
6
1
123
87
6
2
28
53
11
1
3
80
43
20
1
79.4
31.1
22.7
38.7
48.9
1
n/a
141
17
4
1
n/a
147
18
3
1
n/a
104
16
2
2
n/a
125
16
2
73.0
2.7
17.0
17.9
77.1
n/a
10
9
9
4
n/a
12
9
12
5
n/a
15
1
26
26
n/a
27
1
31
18
12.5
33.3
10.6
66.9
44.5
2
29
131
92
3
1
27
151
50
16
15
25
76
30
108
13
34
65
30
76
56.6
28.0
32.9
23.7
59.0
1
7
13
1
11
1
16
7
1
17
3
5
3
27
10
4
2
43
24.6
37.1
29.5
65.9
31.6
16
19
7
170
n/a
21
23
7
236
n/a
12
16
1
79
n/a
15
18
4
102
n/a
37.7
36.2
28.6
14.8
33.3
64
2
44
60
2
58
16
5
13
15
5
16
53
45
232
237
19.8
44.3
27.7
58.6
65.6
44
90
4
58
98
2
13
50
2
12
37
1
35
25
8.6
20.7
4.7
37.5
52.7
155
19
n/a
5
n/a
164
35
n/a
10
n/a
49
6
n/a
8
n/a
21
7
n/a
22
n/a
23.4
50.5
79.1
39.8
27.7
127
Sweden
Switzerland
Syrian Arab Republic
Tajikistan
Thailand
Macedonia, The former Yugoslav Republic of
Togo
Tonga
Trinidad and Tobago
Tunisia
Turkey
Turkmenistan
Tuvalu
Uganda
Ukraine
United Arab Emirates
United Kingdom
United Republic of Tanzania
United States of America
Uruguay
Uzbekistan
Vanuatu
Venezuela, Bolivarian Republic of
Viet Nam
Yemen
Yugoslavia
Zambia
Zimbabwe
128
Total expenditure on
health (per capita at
average exchange rate)
Total expenditure on
pharmaceuticals (% total
expenditure on health)
Total expenditure on
pharmaceuticals (per
capita at exchange rate)
1995
2000
1995
2000
1995
2000
2293
4352
42
4
99
2269
3572
64
5
73
12.3
10
7
41.2
29.7
13.9
10.7
6
13.4
29.3
282
435
3
2
29
315
382
4
1
21
119
12
91
189
136
106
8
81
248
126
11
39.6
26.2
34.9
21.6
18.2
36.8
26.7
37.6
28
13
5
24
66
29
19
3
22
93
33
93
33
63
11
47
150
42
74
14
30
23.2
21.2
n/a
26.4
12.6
28
26.7
n/a
15.4
17.8
21
5
n/a
3
6
58
7
n/a
2
5
617
1372
8
3654
552
820
1786
11
4540
653
15.9
15.3
18.7
8.9
20.2
18.8
14.1
10.4
11.9
17.1
98
209
2
324
112
155
253
1
541
112
22
47
168
11
38
30
47
296
21
21
12.8
20.9
21.7
38.1
37.5
7.6
22.6
14
41
37.8
3
10
36
4
14
2
11
42
9
8
96
19
43
89
18
42
11.2
32.2
13.9
9.6
26.7
20.6
11
6
6
9
5
9
STATISTICAL ANNEX
Government expenditure
on pharmaceuticals (per
capita at exchange rate)
Private expenditure on
pharmaceuticals (per
capita at exchange rate)
Private expenditure
as % total health
spending
1995
2000
1995
2000
207
232
2
75
203
1
1
12
95
150
1
18
221
232
3
1
13
15.7
44.8
48.3
34.0
42.8
11
n/a
16
8
11
13
n/a
11
11
10
3
n/a
8
58
19
7
n/a
10
82
23
15.2
57.2
53.2
56.6
59.6
n/a
3
n/a
1
4
34
5
n/a
3
n/a
2
n/a
2
2
21
1
n/a
2
2
28.5
25.5
28.6
49.3
25.0
n/a
133
1
50
19
n/a
167
1
99
16
n/a
76
1
224
93
n/a
86
1
442
95
20.7
16.3
52.9
54.5
54.1
2
n/a
9
1
1
1
n/a
6
2
1
n/a
28
4
14
1
n/a
35
8
8
17.1
35.8
49.4
79.7
62.1
11
3
4
9
3
7
3
3
1
7
2
2
41.4
43.5
40.9
129
Annex Table 3: 1999 World drug survey access, national medicines policies
DATA FROM 1999 WORLD DRUG SURVEY
Country
Questionnaire
response % with
access to EMs
% with
access
to EMs
Status
of NMP
Date of latest
EM policy
document
1997 int $
Afghanistan
Albania
Algeria
Andorra
Angola
NMP implementation
Drug registration
Date
There is
DRA
Law on
registration
Col H regional
policy
1=yes
1=yes
1995
Yes
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
0
50
60
95
20
5080
5080
>95
<50
4
1
4
5
4
66
70
40
100
100
5080
5080
<50
>95
>95
5
4
1
3
4
Azerbaijan
Bahamas
Bahrain
Bangladesh
Barbados
66
80
100
65
100
5080
5080
>95
5080
>95
5
4
4
2
4
Belarus
Belgium
Belize
Benin
Bhutan
70
99
80
77
85
5080
>95
5080
5080
8195
1
5
4
3
2
1998
1998
1985
1998
Yes
0
1
0
0
1
0
Bolivia
Bosnia and Herzegovina
Botswana
Brazil
Brunei Darussalam
70
88
90
40
99
5080
8195
8195
<50
>95
1
3
3
1
5
1997
1997
1987
1998
1999
Yes
1998
Yes
Yes
1
1
1
1
Bulgaria
Burkina Faso
Burundi
Cambodia
Cameroon
88
60
20
30
66
8195
50-80
<50
<50
5080
5
1
3
1
3
1997
Yes
1995
Yes
1
1
1
1
1
1
0
1
100
80
50
>95
5080
5080
4
5
1
1995
1
1
1
1
1
1
46
<50
1995
88
85
88
90
61
8195
8195
8195
8195
5080
1
1
1
3
1
1996
1997
1993
1997
1997
Cook Islands
Costa Rica
Cte dIvoire
Croatia
Cuba
60
100
80
100
100
5080
>95
5080
>95
>95
4
1
4
3
1
Cyprus
Czech Republic
Democratic Peoples Republic of Korea
Democratic Republic of the Congo
Denmark
100
88
99
>95
8195
4
5
3
3
5
Canada
Cape Verde
Central African Republic
Central America
Chad
Chile
China
Colombia
Comoros
Congo
130
>95
1998
1995
1999
1982
1996
1998
1998
1997
1998
Yes
1997
Yes
1999
Yes
1
1
0
1
Yes
Yes
0
1
1
1
1
0
1
1
1
1
1
1
1
1
1997
1998
1998
1983
1997
1999
1998
STATISTICAL ANNEX
Manufacturing
Date
DRA
registers
drug
Law on
manufacturing
1=yes
1=yes
1=yes
1
1
1
1
1
1
1
1
1
Law on
importation
1=yes
1=yes
1
0
1
1
1
1964
1992
1998
1994
1
1
1
1
1
1
1
1
1
1
1
1
1964
1998
1998
1984
1
1
1
1
1
1
1
1
1964
1995
1998
1997
1
1
1
1
1977
1991
1998
1994
1997
1982
0
1
1
0
0
1
1
0
0
1
1
1
1997
1982
1969
0
1
1
1
1
1
1
1
1987
1997
1982
1969
1
1
1
0
1987
1997
1982
1
1
1
1
1993
1998
1998
1998
1997
0
1
0
0
1
0
0
1
0
1975
0
1
0
1
1
0
1958
1975
0
1
0
1975
0
1
0
1997
1997
1997
1997
1992
1976
1
1
1
1
1
1
1992
1995
1
1
1
1
1992
1996
1
1
1992
1973
1995
1992
1
1
0
1
1
0
0
1
1995
1
0
0
1
1
1
0
1
1995
1998
1
1
0
1
1995
1998
1994
1
1
0
1
1
0
1
1
1993
1994
1
0
1
1
1
1
1
0
0
1
1
0
1993
1
1
0
1993
1
1
1967
1965
1965
1965
1985
1985
1985
1985
1985
1
1
0
1
1
1
1991
1933
1
1
1
1
1990
1933
1
1
1991
1933
1
1
1994
1994
1997
1995
1
1
1
1
1
1
1
1
0
1
1
1
1
1992
1994
1997
1922
0
1
0
1
1
0
1
1
1
1
1994
1994
1997
1995
0
1
1
1
1
1973
1994
1997
1922
1
1
1
0
1995
1997
1
1
1
1
1
1
1990
1998
1
1
1
0
1
1
1993
1998
1
1
1980
1998
1998
Date
Pharma registration
DRA
inspects
manufacturers
1998
1995
Date
Importation
Law on
distribution
Date
1=yes
1980
1998
1969
1
1
1
1=yes
1980
1998
1995
1998
1993
DRA inspects
drug outlets
1
1
0
1
1996
1
0
1
131
Annex Table 3: 1999 World drug survey access, national medicines policies
DATA FROM 1999 WORLD DRUG SURVEY
Country
Questionnaire
response % with
access to EMs
% with
access
to EMs
Status
of NMP
Date of latest
EM policy
document
1997 int $
Djibouti
Dominica
Dominican Republic
Ecuador
Egypt
80
90
66
40
88
5080
8195
50-80
<50
8195
4
4
3
3
5
El Salvador
Equatorial Guinea
Eritrea
Estonia
Ethiopia
80
44
57
100
66
5080
<50
5080
>95
5080
4
1
3
4
1
Fiji
Finland
France
French West Africa
Gabon
100
98
99
>95
>95
>95
1
4
4
1995
30
<50
1993
Gambia
Georgia
Germany
Ghana
Greece
90
30
100
44
100
8195
<50
>95
<50
>95
1
1
4
3
1
1996
1995
98
50
93
44
44
>95
5080
8195
<50
<50
4
1
3
5
5
30
40
100
100
35
<50
<50
>95
>95
<50
1
1
5
4
1
1997
1995
80
85
85
99
99
5080
8195
8195
>95
>95
2
1
1
5
5
1983
1998
1991
99
95
100
100
66
>95
8195
>95
>95
5080
5
1
5
1
1
35
75
99
66
66
<50
5080
>95
5080
5080
1
3
5
1
1
90
88
80
30
100
8195
8195
5080
<50
>95
1
4
3
3
4
Grenada
Guatemala
Guinea
Guinea-Bissau
Guyana
Haiti
Honduras
Hungary
Iceland
India
Indonesia
Iran, Islamic Republic of
Iraq
Ireland
Israel
Italy
Jamaica
Japan
Jordan
Kazakhstan
Kenya
Kiribati
Kuwait
Kyrgyzstan
Lao Peoples Democratic Republic
Latvia
Lebanon
Lesotho
Liberia
Libyan Arab Jamahiriya
132
1997
1998
1990
1997
NMP implementation
Drug registration
Date
There is
DRA
Law on
registration
Col H regional
policy
1=yes
1=yes
1
0
1
1
1
0
0
1
1
1
1
1
1
1
1
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1997
1998
Yes
Yes
1993
1996
1994
Yes
1995
1995
1996
1992
1
1
1
0
1
1
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
Yes
1
1
1
1
1
1
Yes
1
1
1
0
1998
Yes
1997
Yes
1998
Yes
1994
1995
1998
1995
1950
1998
1994
1998
1994
1992
1992
Yes
1995
1999
Yes
1999
1999
Yes
Yes
1
1
0
1
1
1
1
0
1
1
1996
1998
STATISTICAL ANNEX
Manufacturing
Date
DRA
registers
drug
Law on
manufacturing
1=yes
1=yes
1=yes
0
0
1
1
1
1
0
1
1
1
Date
Importation
DRA
inspects
manufacturers
Law on
importation
1=yes
1=yes
1991
1998
1974
1981
1
1
1
1
0
1
1
1
1959
1993
1996
1985
1987
1998
Date
Pharma registration
Law on
distribution
Date
1=yes
1991
DRA inspects
drug outlets
1=yes
1998
1974
1994
1
0
1
1
1
1991
1998
1998
1997
1
0
1
1
1
1
1
1
1
1
1
1959
1991
1993
1991
1
1
1
1
1959
1991
1993
1993
1
1
1
1
1
1
1
1
1
1
1985
1987
1998
1
1
1
1985
1987
1998
1
1
0
1995
1995
1998
1974
1994
1
1
1
1959
1993
1992
1
0
0
1
0
1
1
0
1
1
1987
1994
0
1
1
0
1
1
1
1
1
1995
1984
1992
1
1
1
0
1
1
1
1
1
1984
1996
0
1
1
1
1
1
1984
1996
1
1
1
1984
1996
1
1
1
1992
1987
1995
1997
1994
0
1
0
0
1
1
1997
1984
0
1
1
1997
1984
1
0
1
1
1
1
1
1
1
0
1999
1994
1998
1996
1
1
1
1
1
1999
1994
1998
1997
1
1
1
1
1
1995
1997
1984
0
1
1
0
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1999
1994
1998
1997
1971
1988
1996
1
1
1
1
1
1
1
1
1
1965
1988
1992
1
1
1
1
1
1
1965
1988
1998
1
1
0
1964
1988
1
1
1
1964
1996
1
1
1
1
1
1
1
1
1
1964
1996
1
1
1
1
1
1
1964
1996
1
1
1
1965
1994
1
1
1
1983
1
0
1
0
1
0
1983
1
0
1
1
1983
1981
1
1
1983
1981
1
0
1995
1990
1991
1989
1998
1994
1
1
1
1
1
1
1
0
1
1
1
0
1
1
1995
1994
1973
1
1
0
1
1
1996
1994
1
1
1
1
0
0
1
1994
1994
1999
1973
1
0
0
0
1
1998
1996
1998
1972
1998
1972
1
1
133
Annex Table 3: 1999 World drug survey access, national medicines policies
DATA FROM 1999 WORLD DRUG SURVEY
Country
Questionnaire
response % with
access to EMs
% with
access
to EMs
Status
of NMP
Date of latest
EM policy
document
1997 int $
There is
DRA
Law on
registration
Col H regional
policy
1=yes
1=yes
1997
Yes
1
0
0
1
1
1
0
1
0
1
1
0
0
1
1
1
1
1
1
1
0
Yes
1
1
1
1
1
1
1
1
Yes
Yes
1
1
1
1
1
1
1
1
1
1
0
1
0
1
1
0
1
0
1
1
1997
1997
1998
1
1
1
1
1
0
1
0
1
1
0
0
Lithuania
Luxembourg
Madagascar
Malawi
Malaysia
88
99
65
44
70
8195
>95
5080
<50
5080
5
5
3
1
1
Maldives
Mali
Malta
Marshall Islands
Mauritania
50
60
90
66
5080
5080
3
3
5
4
5
1995
1998
1996
1982
Mauritius
Mexico
Micronesia, Federated States of
Monaco
Mongolia
100
92
95
60
5080
3
3
3
4
3
Morocco
Mozambique
Myanmar
Namibia
Nauru
66
50
60
80
100
5080
5080
5080
5080
5080
5
2
1
1
4
Nepal
Netherlands
New Zealand
Nicaragua
Niger
20
100
100
46
66
<50
>95
>95
<50
5080
1
1
4
1
1
Nigeria
Niue
Norway
Oman
Pakistan
10
95
100
90
65
<50
8195
>95
8195
50-80
1
3
4
3
1
Palau
Panama
Papua New Guinea
Paraguay
Peru
100
80
90
44
60
>95
5080
8195
<50
5080
4
4
1
1
1
Philippines
Poland
Portugal
Qatar
Republic of Korea
66
100
99
99
5080
>95
>95
8195
2
5
1
5
3
66
85
66
44
66
5080
8195
5080
<50
5080
3
3
5
4
4
66
85
100
44
5080
8195
>95
5
4
3
5
5
Republic of Moldova
Romania
Russian Federation
Rwanda
Saint Kitts and Nevis
Saint Lucia
Saint Vincent and the Grenadines
Samoa
San Marino
So Tom and Principe
134
>95
8195
8195
<50
Drug registration
Date
8195
5080
NMP implementation
1998
1991
1991
1998
1997
Yes
Yes
1992
1985
1993
1998
1993
1999
Yes
1995
1994
1996
1995
1998
1990
1997
1997
1999
1998
1998
1997
1997
1998
1987
1998
1997
Yes
STATISTICAL ANNEX
Manufacturing
Date
DRA
registers
drug
Law on
manufacturing
1=yes
1=yes
1
1984
1995
Law on
importation
1=yes
1=yes
1=yes
1=yes
1=yes
1984
1984
1984
0
1
1
1
0
1
1991
0
1
1
1
1993
1994
1
1
1993
1991
1
1
1
1
0
0
0
1
1
0
0
1
1
1
0
1
1
1985
1997
1
1
1985
1998
1997
1998
1
0
1
1
0
0
1
1997
1958
1965
0
1
1
0
0
1
1
0
1
1
1
0
1997
1954
1965
1
1
1
0
1
1
1
0
1997
1958
1965
1981
1963
1984
1998
1
1
1
1
1
1
0
1
1
1
1
1
1981
1963
1984
1998
1
1
1
1
1
1
1
1
1993
1
1
1
1
1
1
1
1
0
1
1
1
1
0
1
1958
1
1
1
1
1
1
1
1
1
1
1
0
1
1
0
1
0
1
1
0
1
0
1
1
1
0
1
1
0
1
0
1
1
1995
1992
1991
1991
1997
1991
1
1
1
1
1
1
1997
1995
1
1
1
1
1997
1992
1
1
1997
1995
1
1
1998
1
0
0
0
1
0
1998
1
0
1998
1
0
1998
0
0
0
0
0
0
1994
1994
1987
1976
1993
1997
1997
1994
1976
1997
1994
1997
0
0
Date
Pharma registration
DRA
inspects
manufacturers
1985
1998
Date
Importation
Law on
distribution
Date
0
1985
1998
1
1
1997
1
1
1
1
1
0
1997
1958
1965
1
1
1
1
1981
1963
1984
1998
1
1
1
1
1981
1963
1984
1998
1
1
1
1
1958
1
1
1
1
1
1958
1
1
1
1
1
1
1
0
1
1
1984
1963
1992
1994
1973
1976
1963
1990
1997
1
1
0
1
0
DRA inspects
drug outlets
1994
1973
1976
1995
1997
0
0
0
1
1
1
1
0
135
Annex Table 3: 1999 World drug survey access, national medicines policies
DATA FROM 1999 WORLD DRUG SURVEY
Country
Questionnaire
response % with
access to EMs
% with
access
to EMs
Status
of NMP
Date of latest
EM policy
document
1997 int $
Saudi Arabia
Senegal
Seychelles
Sierra Leone
Singapore
99
66
88
44
100
>95
5080
8195
<50
>95
5
1
5
1
4
>95
>95
5080
<50
5080
1
5
4
3
1
Spain
Sri Lanka
Sudan
Suriname
Swaziland
100
95
15
100
100
>95
8195
<50
>95
>95
4
1
1
1
3
Sweden
Switzerland
Syrian Arab Republic
Tajikistan
Thailand
99
100
80
44
95
>95
>95
5080
<50
8195
4
4
1
1
1
66
70
98
77
51
5080
5080
>95
5080
5080
4
1
4
1
4
Turkey
Turkmenistan
Tuvalu
Uganda
Ukraine
99
66
90
70
66
>95
5080
8195
5080
5080
4
1
4
1
5
99
99
66
99
66
>95
>95
5080
>95
5080
5
5
1
5
5
Uzbekistan
Vanuatu
Venezuela, Bolivarian Republic of
Viet Nam
Yemen
66
90
85
50
5080
8195
8195
5080
5
5
3
1
1
1995
1996
1998
Yugoslavia
Zambia
Zimbabwe
80
66
70
5080
5080
5080
3
1
1
1998
1996
1995
Slovakia
Slovenia
Solomon Islands
Somalia
South Africa
136
1995
NMP implementation
Drug registration
Date
There is
DRA
Law on
registration
Col H regional
policy
1=yes
1=yes
1998
Yes
1993
1997
1997
Yes
1
1
1
1
1
0
1990
1996
1998
Yes
1994
1997
1997
1998
1
1
1
1
0
1
1
1
1
1
1995
1
1
1
1
1
0
1
1
1
1
1
1
0
1
1
0
1
0
1
1
1
1
1
1
1
1993
1996
Yes
1997
1998
1998
1992
Yes
1997
1993
1994
Yes
1993
1996
1998
Yes
STATISTICAL ANNEX
Manufacturing
Date
DRA
registers
drug
Law on
manufacturing
1=yes
1=yes
1=yes
1954
1985
1997
1996
1
1
0
1998
1990
Law on
importation
1=yes
1=yes
1954
1954
1954
1985
1985
1985
1
1
0
1
1
0
1997
1996
1
1
0
1
1
1
1997
1996
1960
1
1
1
1997
1996
1960
1
1
1
1998
1998
1998
1
1
1
1
0
1
1
1
1
0
1
1
1
0
1
1990
1
1
1
0
1
1990
1998
1
1
1
0
1
1990
1998
1
1
1
0
0
1998
1
1
0
0
0
1995
1995
1
1
1
1
1
1
1
1
1
1995
1995
1952
1
1
1
1
1
1
1997
1976
1965
1
1
0
1997
1976
1
0
1987
1987
1987
1987
1998
1993
1
1
0
1
1
1
1
0
1
1
1998
1
1
0
1
1
1961
1
1
0
1
1
1998
1996
1985
1
1
0
1
1
1998
1996
1990
1
1
0
1
1
1960
1
1
0
1
0
1995
1995
1984
1928
1993
0
1
0
1
0
1
1993
0
1
0
1
1993
0
1
1993
0
1
1997
1998
1997
1998
1996
1999
1
1
1
1
1
1
1
1
1
1997
1996
1999
1
1
1
0
1
1
1989
1999
0
1
1
1992
1999
1
1
1
1993
1993
1993
1993
1997
1997
1998
1991
1974
Date
Pharma registration
DRA
inspects
manufacturers
1974
1973
1998
Date
Importation
Law on
distribution
Date
1=yes
1974
DRA inspects
drug outlets
1=yes
1963
137
Annex Table 4: 1999 World drug survey quality control, essential medicines lists, procurement
DATA FROM 1999 WORLD DRUG SURVEY
Country
Regulation of promotion
Law on
promotion
Date
1=yes
Afghanistan
Albania
Algeria
Andorra
Angola
1
1
1
1980
1998
1992
Public finance
Requirements
for registration
Testing at:
Drugs are
Generic
covered in pub- substitution
lic insurance
public (1)
1=yes; 0=no
public (1);
private (2)
1
134
3
1
14
1
12
12
13
12
134
1234
12
34
1
1
13
1
1
0
1
3
12
12
3
123
12
12
12
12
1
0
1
0
Azerbaijan
Bahamas
Bahrain
Bangladesh
Barbados
0
1
1
1
1997
1982
1969
12
123
2
123
2
134
1234
24
1
4
4
1
1
0
0
12
1
12
12
Belarus
Belgium
Belize
Benin
Bhutan
1997
123
12
0
1
0
1975
3
12
12
2
123
2
0
0
12
1
12
Bolivia
Bosnia and Herzegovina
Botswana
Brazil
Brunei Darussalam
1997
12
134
14
12
1
1
1992
1999
123
12
1234
14
1
12
Bulgaria
Burkina Faso
Burundi
Cambodia
Cameroon
1
1
0
1
1995
1998
123
123
1234
1
4
1994
13
Canada
Cape Verde
Central African Republic
Central America
Chad
1
1
0
1993
Chile
China
Colombia
Comoros
Congo
1998
0
234
1
0
12
12
12
12
1
12
123
1
4
1
0
0
12
12
12
1965
1985
123
1234
0
1
1933
123
1234
234
0
0
3
3
1994
1998
1997
3
1
12
123
12
0
234
23
1234
4
1
124
1
1
1
1
1
1
12
2
12
3
3
123
1
234
124
14
1
0
1
1
3
Cook Islands
Costa Rica
Cte dIvoire
Croatia
Cuba
0
1
1
1
0
Cyprus
Czech Republic
Democratic Peoples Republic of Korea
Democratic Republic of the Congo
Denmark
1
0
138
1964
1960
STATISTICAL ANNEX
EML
last update
Av no. medicines
on EML
National
tender
Public proc.
Limited to
drugs in EML
1=yes
1995
2000
1997
356
295
1100
1977
1996
National list of
registered drugs
Regulate manuf.
ex.fact.price (1); Max
retail markup (2);
Max wholesale
markup (3); None (4)
1=yes; 2=no
Prescribers
and dispensers
Essential drug part
of curricula: medicine (1), nursing (2),
pharmacy (3);
Pharm aides (4)
0
0
1
Price
regulation
2
23
23
1986
1
123
1
1986
12
23
0
1
1
1989
1998
1999
123
123
1
1
1234
123
4
123
2
3
2
1
1
2
1234
123
4
123
2
2
1
2
1994
1988
1998
1999
278
531
1995
1998
1997
1982
1998
807
1800
150
1200
1998
400
1997
1997
1997
70
100
90
30
220
337
1
0
1
1998
3
12
24
252
20
80
1996
13
520
305
100
1998
1989
234
3
4
2
1
1
1
1
1
1
1995
1984
1989
1994
1993
13
1234
3
123
1
4
4
1
1
2
1
1998
1995
1992
1999
1997
1997
1994
1997
1995
70
241
227
500
274
50
100
45
100
60
95
50
100
100
50
0
1
1
1
13
1234
13
1234
1987
2000
1998
1996
641
222
12
42
0
1
1
1993
24
12
1
2
4
1
2
1
1996
270
100
1998
1842
15
85
13
123
123
2
123
1
1
4
4
123
3
123
1
1
1
1
123
123
1
1
1996
1998
1990
1998
1982
1991
0
0
186
1997
1997
1997
1998
1994
344
583
137
1366
904
100
1996
2000
1991
1979
1000
100
80
100
100
10
0
1
1
0
1
0
0
1997
1997
1998
1994
123
3
13
13
139
Annex Table 4: 1999 World drug survey quality control, essential medicines lists, procurement
DATA FROM 1999 WORLD DRUG SURVEY
Country
Regulation of promotion
Law on
promotion
Date
1=yes
Public finance
Requirements
for registration
Testing at:
Drugs are
Generic
covered in pub- substitution
lic insurance
public (1)
1=yes; 0=no
0
23
0
134
4
13
1
12
1
0
1
1
12
12
12
12
12
134
14
1
1
1
0
1
2
12
12
2
0
1
1
1
3
public (1);
private (2)
Djibouti
Dominica
Dominican Republic
Ecuador
Egypt
0
0
1
1
1
1998
1974
1994
13
23
12
El Salvador
Equatorial Guinea
Eritrea
Estonia
Ethiopia
1
1
1
1
1988
1991
1993
1994
12
123
12
1234
24
24
134
Fiji
Finland
France
French West Africa
Gabon
1
1
1
1985
1998
1994
1
13
2
14
1234
1
1
1995
123
234
Gambia
Georgia
Germany
Ghana
Greece
1
1
1
1984
1996
2
123
13
0
3
124
1
1
0
1
12
1234
123
1993
Grenada
Guatemala
Guinea
Guinea-Bissau
Guyana
1
1
1
1986
1997
1984
Haiti
Honduras
Hungary
Iceland
India
1
1
1
1
1
Indonesia
Iran, Islamic Republic of
Iraq
Ireland
Israel
Italy
Jamaica
Japan
Jordan
Kazakhstan
3
1
12
3
123
123
123
3
1
12
1
0
1
3
12
1999
1994
1997
1995
3
123
1
123
1
0
23
134
134
3
34
1
24
1
0
1
1
1
1
1
12
2
12
3
1
0
1
1971
12
123
123
1234
14
123
1
1
1
1
1
1
1
0
1964
1983
12
1
123
1234
1234
1234
14
1
1
0
1
1
12
3
1
12
1
1998
12
Kenya
Kiribati
Kuwait
Kyrgyzstan
Lao Peoples Democratic Republic
1
0
1983
23
12
2
2
1997
12
1234
12
Latvia
Lebanon
Lesotho
Liberia
Libyan Arab Jamahiriya
1
0
0
1
1
1995
12
3
3
123
12
1234
1234
124
34
234
1
1
4
4
124
1
1
12
140
1998
1972
12
1
12
STATISTICAL ANNEX
EML
last update
Av no. medicines
on EML
National
tender
Public proc.
Limited to
drugs in EML
1=yes
1977
1998
1997
1996
1998
412
350
306
35
80
20
100
80
1991
1996
1996
2000
1989
95
134
313
179
99
1
1996
450
100
1997
184
80
1997
1999
250
253
100
3
1996
1998
3280
1
0
0
0
0
1
1
1
0
20
1998
1994
1996
1990
1997
271
470
165
90
1996
1997
1997
155
365
750
1998
350
1998
1998
1996
487
1483
1773
7
80
1998
494
98
70
100
30
0
0
1
National list of
registered drugs
Regulate manuf.
ex.fact.price (1); Max
retail markup (2);
Max wholesale
markup (3); None (4)
1=yes; 2=no
Prescribers
and dispensers
Essential drug part
of curricula: medicine (1), nursing (2),
pharmacy (3);
Pharm aides (4)
2
3
3
123
13
4
4
12
12
3
1993
1999
1998
1998
24
4
23
23
1
2
2
1
123
23
2
1
1
12
4
4
4
1
1
1
123
3
13
4
4
123
2
1
1
4
23
23
23
2
1
1
1
1
1
1
1
1
1998
1996
1998
1994
0
1
0
0
Price
regulation
1998
1995
1995
1995
1994
1
1
1
1990
90
10
100
1
40
0
1
0
0
0
1998
1998
1997
1997
100
93
20
1
1
1
1997
1990
1234
12
23
2
1
0
0
1234
1234
4
1
23
1
1
1
1234
123
1
2
13
1998
1995
325
42
58
1993
1998
1996
2000
1997
330
240
91
80
365
100
1998
34
1994
1992
1990
1998
1997
257
370
256
149
911
100
96
0
0
0
1
1
1996
13
13
23
34
1234
23
23
4
4
12
1
1
1
1
1994
1993
100
1986
1993
1
1
141
Annex Table 4: 1999 World drug survey quality control, essential medicines lists, procurement
DATA FROM 1999 WORLD DRUG SURVEY
Country
Regulation of promotion
Law on
promotion
Lithuania
Luxembourg
Madagascar
Malawi
Malaysia
Date
Public finance
Requirements
for registration
Testing at:
1=yes
123
23
Drugs are
Generic
covered in pub- substitution
lic insurance
public (1)
1=yes; 0=no
public (1);
private (2)
12
1953
123
1234
12
Maldives
Mali
Malta
Marshall Islands
Mauritania
1
1
1993
1986
12
12
4
134
4
1
3
2
12
Mauritius
Mexico
Micronesia, Federated States of
Monaco
Mongolia
1
1
0
1
1
234
123
4
4
1
0
1
0
1
1
2
12
3
12
Morocco
Mozambique
Myanmar
Namibia
Nauru
12
12
1
12
0
1985
1993
123
123
1997
1998
12
12
1234
124
4
12
134
1
1
1
0
1997
1954
1965
12
12
123
2
12
3
0
0
4
34
0
1
1
0
Nepal
Netherlands
New Zealand
Nicaragua
Niger
1
1
1
1
1978
1963
1984
1998
13
3
13
123
134
14
12346
1234
14
1
3
12
1
1
0
1
12
12
12
Nigeria
Niue
Norway
Oman
Pakistan
1
1
1
0
1
1993
123
2
13
123
123
1234
1
1234
124
1
4
1
14
1
0
1
0
1
12
1
3
1
12
Palau
Panama
Papua New Guinea
Paraguay
Peru
0
1
0
1
1
2
12
12
2
12
0
1234
2
3
124
2
13
1
1
0
0
1
1
1
12
3
12
Philippines
Poland
Portugal
Qatar
Republic of Korea
12
1234
12
12
12
Republic of Moldova
Romania
Russian Federation
Rwanda
Saint Kitts and Nevis
Saint Lucia
Saint Vincent and the Grenadines
Samoa
San Marino
So Tom and Principe
142
1994
1976
1992
1997
1997
4
1
1994
13
1
1
1997
1994
12
12
1234
1234
1
1
1
1
12
12
1
0
1998
23
12
14
2
34
12
12
2
0
4
4
0
0
12
1
STATISTICAL ANNEX
EML
last update
Av no. medicines
on EML
National
tender
Public proc.
Limited to
drugs in EML
1=yes
Price
regulation
National list of
registered drugs
Regulate manuf.
ex.fact.price (1); Max
retail markup (2);
Max wholesale
markup (3); None (4)
1=yes; 2=no
Prescribers
and dispensers
Essential drug part
of curricula: medicine (1), nursing (2),
pharmacy (3);
Pharm aides (4)
2000
1995
1995
1989
245
1998
1997
247
333
100
450
1994
24
2
2
4
2
1
13
1234
1
1
2
2
2
0
80
0
1
100
1992
1998
1995
650
776
95
10
90
1996
6000
1991
1984
1998
1996
480
184
585
1997
262
1994
1998
1994
348
100
1995
1
1
1
0
0
1997
1994
123
123
4
3
4
1
1
1
0
1987
1998
1994
1234
1234
4
3
2
4
4
4
2
1
1
2
85
3
1234
100
100
0
1
1996
1998
1998
1998
1994
4
3
1
23
1
1
1
1
1
1
0
1
0
1989
34
123
4
2
12
4
2
1
1
1
1
1
1234
4
4
1
2
4
1
2
1
1
100
100
1234
13
1996
1998
2000
1995
1996
448
277
10
100
90
870
470
58
42
80
1998
1993
1996
400
216
379
10
1998
459
1
0
1
0
1
1997
1995
517
1989
1998
13
123
1
0
1997
1234
13
23
123
1
1
1
1
23
1
2
0
1
3
123
4
1
2
2
1996
1994
2000
1998
1998
1994
1994
1998
100
100
209
2348
40
134
250
90
60
100
100
1998
4
1993
24
143
Annex Table 4: 1999 World drug survey quality control, essential medicines lists, procurement
DATA FROM 1999 WORLD DRUG SURVEY
Country
Regulation of promotion
Law on
promotion
Date
1=yes
Saudi Arabia
Senegal
Seychelles
Sierra Leone
Singapore
Public finance
Requirements
for registration
Testing at:
Drugs are
Generic
covered in pub- substitution
lic insurance
public (1)
1=yes; 0=no
public (1);
private (2)
1954
12
1985
123
1234
13
12
1
123
134
234
1
1
34
1
1
1
3
12
1
Slovakia
Slovenia
Solomon Islands
Somalia
South Africa
1
1
1
1997
1997
1960
1998
1234
12
Spain
Sri Lanka
Sudan
Suriname
Swaziland
1
1
1
0
1
1990
1234
23
1234
3
2
1
1
1
1
1
1
1
1
0
12
1978
12
13
123
23
Sweden
Switzerland
Syrian Arab Republic
Tajikistan
Thailand
1
1
1
1993
1995
1965
1
13
12
123
123
1234
134
13
1
1
12
3
1987
123
1234
12
1
1
0
1
1
1998
1996
134
3
4
1
1
0
0
1990
123
1
1
12
12
3
1234
14
1
12
1
12
1
1
1990
12
23
0
1
1993
123
0
347
12
1997
12
12
1
1
1
1998
1997
1999
1
12
12
13
1234
1234
1
1
14
1
1
0
3
12
12
1993
12
134
12
12
1998
123
1234
144
1998
12
12
1
3
12
12
12
STATISTICAL ANNEX
EML
last update
Av no. medicines
on EML
National
tender
Public proc.
Limited to
drugs in EML
1=yes
1989
1998
1988
1992
1998
100
1992
1988
National list of
registered drugs
Regulate manuf.
ex.fact.price (1); Max
retail markup (2);
Max wholesale
markup (3); None (4)
1=yes; 2=no
Prescribers
and dispensers
Essential drug part
of curricula: medicine (1), nursing (2),
pharmacy (3);
Pharm aides (4)
Price
regulation
123
603
92
1998
123
1994
1996
1996
800
70
30
1997
13
350
100
1
0
1
1988
234
1
3
4
1
1
2
1998
750
1998
1234
13
123
123
2
23
4
4
1
1
1
1
2
1
23
1
1
1
1998
1995
1997
1998
95
0
1
0
1
1994
1991
1998
1989
750
0
0
1
1998
1998
1998
1234
377
1998
1234
1993
3
123
123
23
4
23
123
1
1
2
1
1
123
4
4
2
1
3
1234
1234
23
4
2
1
1
1
123
1234
792
300
350
90
52
90
100
48
10
2000
1998
2000
1993
2000
1995
1996
1998
1991
155
420
988
90
100
10
100
40
0
1
1
1
0
4
2
12
1995
2000
1996
1996
335
100
90
10
0
1
1991
1993
1234
1991
1998
1980
1996
1981
1993
1998
1996
1998
1990
1994
896
325
280
100
0
1
1
535
100
592
40
60
1993
1995
1996
1990
1998
*6/2/03
145