Pitfalls In Management Systems And Quality Of Anti-tb Drug In Lower Southern Thailand Rookkapan K.1, Chongsuvivatwong V. 1, Kasiwong S.2, Pariyawatee S.3, Kasetcharoen Y. 4 , Pungrassami P. 4. Epidemilogy Unit, Faculty of Medicine 1, Faculty of Pharmaceutical Sciences2, Prince of Songkla University (PSU), Regional Medical Science Center, Songkhla 3. Tuberculosis Center 12 Yala 4, Thailand. Problem statement: There are anecdotal reports that deteriorated anti-TB drug were dispensed from Thai hospitals. This information needs verification along with management evaluation. Objectives: To analyze quality of anti-TB drugs, to describe its management system, and to propose strategic management response. Design: Cross-sectional study using questionnaire interview, in-depth interview, document review, inspection of drug inventory, examine physical characteristics of drugs, and laboratory analysis of drug samples. Setting and Population: Data were obtained from 52 facilities: the Tuberculosis Cluster Office in Bangkok, Regional Office of Disease Control, TB Center, 7 provincial health offices, 2 regional hospitals, 8 general hospitals, and 38 randomly selected community hospitals in Region 12. Key informants were persons responsible for anti-TB drug management. From these settings, 4 first-line anti-TB drugs were sampled for laboratory analysis and 280 TB patients were interviewed. Results: Among 52 facilities, at least one kind of deteriorated anti-TB drug was encountered by the responsible officers in 44 facilities within the past years, found in 28 of the inspected drug inventories, and reported by 44 (15.7%) of the TB patients. Percentage of failure in active ingredient test for rifampicin, ethembutol, pyrazinamide, and isoniazid were 0, 14, 0, and 0, and for dissolution test were 62, 0, 26, and 0 respectively. Numbers of facilities with the following drug storage problems: no air-conditioning, temperature more than 30 o C, humidity more than 75% relative humidity, kept ATBDs where sunlight shone out to drug shelves. had water sink near drug shelf, not using first-in first-out system, and containing expired drugs in stock were 22, 7, 24, 5, 19, 20, and 12, respectively. All observed 300 mg rifampicin capsules were kept in non-light resistant plastic bags or bottles during dispensing. Thirteen facilities removed coated ethambutol from the foil and 11 facilities bisected the tablet before dispensing. Conclusions: Sub-standard anti-TB drugs is a serious problem. Anti-TB drugs in the study area were not managed properly. Further improvements are needed to strengthen drug quality assurance systems, drug management, and supervision. Funding sources: World Health Organization (Thailand), Ministry of University Affairs, and PSU

Introduction by inspection: 1/3 hospitals ATBDs* are important weapon for treat & control TB Improper handling of ATBDs may lead to MDR-TB Pilot study (2000) revealed deteriorated** ATBDs by inspection: 1/3 hospitals by interview: 7/13 hospitals, 2/7 PHOs#, 2/2 TB centers 9/51 of TB patients This information needs verification along with management evaluation * ATBD: anti-tuberculosis drug ** Deteriorate: denature while expiry date is not reach # PHO: Provincial Health Office

Logistics chain of ATBD Manufacturer TB cluster Office of disease control TB center PHO* Hospitals Hospitals National level Regional level Provincial level District level Health centers Patients *PHO: provincial health office

Objectives 1. To systematically verify deterioration of ATBDs 2. To evaluate management systems of ATBDs 3. To workout the solutions

Methodology Study design: cross-sectional survey & qualitative study Settings: facilities involved in treatment and supply of ATBDs at national, regional, provincial, and district levels Methods: laboratory analysis of ATBDs, grossly inspection, document review, questionnaire interview, in-depth interview, observe ATBD inventories Informants: ATBD managers, TB patients

Interview 5 TB patients/hospital Sample size TB cluster, office of disease control, TB center, 7 PHOs, University hospital, 8 general hospitals, 2 regional hospitals (n=52) 69 community hospitals Sampling 38 community hospitals Sampled 50 tablets each of R, E, Z, H from dispensing shelves to analyze -Interview ATBD managers -inspect ATBD inventories Interview 5 TB patients/hospital LQAS*: Lot Quality Assurance Sampling R: Rifampicin, E:Ethembutol, Z:Pyrazinamide, H: Isoniazid

Results: deteriorated ATBDs Stained E at the bottom of paper box Discolor Z majority showed abnormal dissolution Normal Z Even non-sticky one had reduce content PAS with broken surface E with sticky coated

Deteriorated ATBDs Methods of Number.hospitals/institutes found data collection deteriorated ATBDs (n=52) R E Z H Any drug Interview manager 6/52 27/52 28/52 16/52 44/52 Grossly inspection 1/52 23/52 9/52 2/52 28/52 Assay test 0/50 7/51 0/46 0/51 7/52 Dissolution test 31/50 0/51 12/46 0/51 38/52

Management factors (number of facilities) Transportation Storage Sunlight shone out to drug storage (5) Non-light nor moisture resistant package (25) sink near drug shelf (19) Not using FIFO system (20) Containing expired drug in stock (12) Temperature>30ο C (7) Poorly sealed package (32) Humidity >75%RH (15) Dispensing Remove coated E from foil (13) Transparent plastic bag for R300 (51) Biseceted coated E (11)

Pitfalls in management Pitfalls in management Hospitals/Institutes (%) Open bulk package 32 (61%) Bulk package using plastic bag 25 (48%) Have a sink near drug shelf 19 (37%) Not using FIFO system 20 (38%) Humidity >75%RH 15 (29%) Containing expired ATBD in stock 12 (23%) Temperature>30 οC 7 (14%) Sunlight exposure to ATBD storage 5 (10%) FIFO: first-expiry in first out

Patient interview (n=280) Experience of deteriorated ATBDs No. of patients Ever found abnormal ATBDs 44 (15.7%) continue taking medicine 20 took only normal tablets/capsules 5 return all ATBDs to hospitals 19 Not finding abnormal ATBDs 236 if found: continue taking medicine 14 took only normal tablet/capsules 6 return all ATBDs to hospitals 208 Ever kept ATBDs in hot place 29 Ever kept ATBDs expose to sunlight 18

Conclusions & Recommendations Sub-standard ATBDs is a serious problem ATBDs in study area were not managed properly We have to improve system of drug management which include transportation, storage, dispensing and attitude. These need multi-disciplinary effort. Policies are urgently needed to strengthen drug quality assurance, drug management standard, and supervision standard