Transcript Quality of Drugs in Private Pharmacies in Laos

Quality of Drugs in Private Pharmacies in Laos: A Repeated Study in 1997 and 1999
Stålsby Lundborg C, Syhakhang L, Lindgren B, Tomson G
International Health Care Research (IHCAR), Karolinska Institutet, Sweden; Ministry
of Health, Laos
Problem Statement: Substandard and counterfeit drugs have been reported in developing
countries, including Laos. The use of these drugs can result in adverse clinical outcomes, such
as lack of effect, risk for development of bacterial resistance, toxicity, or side effects, all
contributing to the burden of disease. Sharing borders with five countries, in which the quality
of drugs is of great concern, Laos faces serious problems in controlling the flow of poorquality drugs. There are few studies systematically examining drug quality.
Objectives: To present repeated quality tests for ampicillin, tetracycline, chloroquine, and
acetylsalicylic acid (ASA) from private pharmacies in Laos in 1997 and 1999, and to discuss
the quality in relation to the National Drug Policy Program.
Design: Quasi-experimental study. Before and after study without control group.
Setting and Population: A total of 115 of 214 licensed private pharmacies were selected in
the Savannakhet province, a pilot province in the Laos National Drug Policy Program. At
each pharmacy, the four drugs were collected, if available. Thirty tablets of each drug were
taken from a selected container. In 1997, 366 samples were analysed; and in 1999, 300.
Intervention: Regulatory intervention within the National Drug Policy Progam (NDPP)
funded by the Swedish International Development and Cooperation Agency (SIDA), and
additional intervention from a randomized trial study funded by the Swedish Agency for
Research Cooperation with Developing Countries (SAREC). The intervention included four
inspections of pharmacies, information, distribution of regulation documents, and sanctions.
Outcome Measures: Percentage of substandard drugs in 1997 and 1999. Identity, assay
(content of active component), and measurement of weight variation tests were performed.
Drug quality was compared mainly according to the standards of the British and U.S.
pharmacopoeias.
Results: The percentage of substandard drugs decreased significantly, from 46% to 22%,
between 1997 and 1999 (p<0.001). Substandard ampicillin and tetracycline were reduced
significantly, from 67% to 9% and from 38% to 12%, respectively (p<0.001). In total, 3% vs.
1% contained no active ingredient, 12% vs. 4% had too little or too much active ingredient,
and 35% vs. 14% had weight variation outside pharmacopoeial limits. There were no changes
regarding chloroquine and ASA.
Conclusions: Drug quality was improved. It is likely that the ongoing National Drug Policy
Program has affected drug quality through improved manufacturing practices and import
procedures. However, the prevalence of substandard drugs was still unacceptably high, which
may result in adverse clinical effects or treatment failure for individual patients.
Background
• Substandard or counterfeit drugs has
been reported in countries where
drug regulations are ineffective
• Use of low quality drugs can result
in adverse clinical outcomes such as
– lack of effect
– risk for development of bacterial
resistance
– toxicity or side effects
• Few studies systematically examines
drug quality
Background, Laos
• Population 5.1 mill
(2000)
– Under 5 mortality rate 106/1000 (2001)
– Life expectancy male 57 y, female 61 y
(2001)
3000 pharmaceutical
preparations
- 70% imported by 30
licensed companies
- 30% domestic
- distribution through > 2000
licensed private pharmacies
- 60% of drug sellers report
buying of drugs from nonlicensed sources
Aim
• To present repeated quality test of
the selected essential drugs
– ampicillin 250 mg tablets/capsules
– tetracycline 250 mg tablets/capsules
– chloroquine 250 mg tablets/sugar
coated tablets
– acetyl salicylic acid (ASA) 300 mg
tablets
in private pharmacies in
Savannakhet province in 1997 and
1999
• To discuss quality in relation to the
National Drug Policy Programme
(NDPP)
Setting and study population
• A random selection of 115 out of 214
pharmacies in Savannakhet province
• At each pharmacy 30 tablets (if
available) were collected from a
selected container of each of the four
drugs
• Tablets were in 1997 collected from
106 pharmacies (92%), 366 samples
and in 1999 from 92 pharmacies (80%),
300 samples
• Regulatory intervention within NDPP
(inspections, information, distribution
of legal documents, sanction)
Analyses
• Identity
• Content of active ingredient (assay)
• Weight variation
In 1999 also
• Free salicylic acid
• Disintegration test
Tests according to British or US
pharmacoepeias except for weight
variation (10 instead of 20 tablets)
Results
Total percentage substandard
drugs
– 1997, 46% (169/366)
– 1999, 22% (66/300)
p<0.001
Ampicillin
Tetracycline
Chloroquine
ASA
1997
1999
67
38
50
25
9
12
42
25
p<0.001
p<0.001
ns
ns
ei
gh
t
ac
tiv
ei
ng
ou
ts
id
e
lim
its
/a
bo
ve
re
di
en
t
ng
re
di
en
tb
el
ow
o
va
ri
at
io
n
ct
iv
ei
W
A
N
Reasons of substandard drugs
35
30
25
20
15
10
5
0
1997 (%)
1999 (%)
Origin of drugs
50
45
40
35
30
25
20
15
10
5
n
U
nk
no
w
nd
la
Th
ai
tn
am
V
ie
La
os
0
1997 (%)
1999 (%)
Substandard drugs by origin
in 1999
• 47% of drugs from unknown
origin (17/36)
• 17 % of drugs from Thailand
(24/143)
• 24% of drugs from Lao
factories (23/97)
71% (55/77) of ampicillin in
1999 was from Laos only 2
were substandard
Conclusions
• A significant reduction in low
quality ampicillin and tetracycline
was seen between 1997 and 1999
• Manufacturing practice in Lao
probably improved as almost all
ampicillin from Laos were of good
quality
• Despite improvements the
prevalence of substandard drugs
were unacceptably high (22%)
Implications and Reference
• For an individual patient the use of a
substandard drug could have serious
clinical consequences. It is thus
important to ensure high quality of
drugs.
• It is important to strengthen both Good
Manufacturing Practice (GMP) and
requirements for imported drugs.
• Studies from other countries are
needed. We found no study with
repeated measurements.
Syhakhang L, Stålsby Lundborg C, Lindgren B,
Tomson G. The quality of drugs in private
pharmacies in Lao PDR: A repeated study in 1997
and 1999. Pharmacy World and Science 2004
(accepted ).