1. 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 poor- quality 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.

2. 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

3. 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 non- licensed sources

4. 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)

5. 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)

6. 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)

7. Results Total percentage substandard drugs –1997, 46% (169/366) –1999, 22% (66/300) p<0.001 1997 1999 Ampicillin 67 9 p<0.001 Tetracycline 38 12 p<0.001 Chloroquine 50 42 ns ASA 25 25 ns

8. Reasons of substandard drugs

9. Origin of drugs

10. 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

11. 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%)

12. 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 ).