1. Quality Assurance of Medicines under Universal Health Coverage Program by Siriwat Tiptaradol (Presenter) Duangporn Abhigantaphand Sooksri Ungboriboonpisal ICIUM 2004 Mar. 31,2004 Department of Medical Sciences Chiangmai, Thailand. Ministry of Public Health

2. Agenda Introduction Objective Methodology Result & Discussion Conclusion Acknowledgement

3. Introduction Year 2001 - The Universal Health Coverage Program so called “30 Baht Co-payment Scheme” was initiated. Year 2002 - The program has covered all 76 provinces to all Thai people. - Budgeting and administrative system has to be adjusted. - Drug price competition and significant cost reduction to hospital drug procurement. - There are rising concerns whether quality of drug products would be compromised.

4. Drug Quality Control Surveillance Network The parties concerned were : Department of Medical Sciences ( as the National Drug Quality Control Lab.) Provincial Public Health Officers Thai FDA Government hospitals

5. Objective To assess the quality of essential drugs. To assess the quality of registered herbal products. To develop drug quality database.

6. Methodology The surveillance study was prospectively designed performed during Oct. 2002 to Sep. 2003 20 drug products (24 dosage forms) were selected from the National Essential Drug List. any registered herbal products which were solid dosage form. The analysis were performed according to USP 24 and BP 2001.

7. Methodology (cont.) All parties concerned were contacted and informed about - details of the project - sampling requirements - procedures.

8. Methodology (cont.) Drug products were selected based on Their importance in terms of public health Wide usage Wide cost differential among products (Innovator and local manufacturers) Quality problem reporting products Stability problems.

9. Sampling requirements 20 drug products in various dosage forms were collected from pharmacy unit in government hospitals and drug stores. Registered herbal products were collected from marketplace. Samples were sent to the Bureau of Drug and Narcotic, as well as Regional Medical Sciences Center, Department of Medical Sciences,for analysis.

10. Quality Control and Specification Method and Standard Specification ( USP 24, BP 2001 ) Identity Assay Dissolution Related substances Content uniformity Microbial contamination ( for any herbal products )

11. List of Drug Products Tested Wide usage criterion : Acyclovir Tab / cap. Amoxycillin Tab. Cimetidine Tab. Co-trimoxazole Tab. Glibenclamide Tab. Metronidazole Tab.

12. List of Drug Products Tested (cont.) Stability problem criterion : Aminophylline Tab. Amoxycillin and Clavulanate pot. Tab/dry syrup. Ampicillin sodium Cap. Glipizide Tab.

13. Quality Problem Criterion : Colchicine 0.6 mg/tab. (Low dose) Diclofenac sodium tab/inj (Dissolution/LAL Test) Diltiazem tab. (Dissolution revision in current pharmacopeia) Gemfibrozil tab/cap. (Dissolution) Indomethacin cap. (Dissolution) Paracetamol inj (LAL Test) List of Drug Products Tested. (cont.)

14. Analysis results A Total of 1,063 Samples of 24 dosage forms and herbal products were evaluated. - 9 dosage forms of 320 samples were conformed to the standard requirements: -Amoxycillin cap - Acyclovir cap ( only 1 sample ) -Ampicillin cap - Diclofenac sodium Inj -Glibenclamide tab - Glipizide tab -Isoniazid tab - Metronidazole tab -Paracetamol inj

15. Analysis results (cont.) For dissolution problem : Indomethacin Cap. (50% Failed, 29 out of 58 samples) (due to less water soluble of active ingredient) Omeprazole Cap. (23% Failed, 11 out of 47 samples) (due to enteric coated and instability of granules) Diclofenac sod.Tab. (22% Failed, 10 out of 46 samples) (due to enteric coated of tablet) Diltiazem Tab. (13% Failed, 5 out of 38 samples) (due to revision of dissolution specification in current pharmacopoeia)

16. Analysis results (cont.) For uniformity of content problems: Colchicine 0.6 mg tab (61% Failed, 39 out of 64 samples, due to low dose and control of raw material ) Aminophylline Tab (12% Failed, 12 out of 98 samples, also due to dissolution and stability problems ) All details are presented in Table 2

17. Analysis results (cont.) About Manufacturers Diltiazem Tab. - 2 out of 7 importers failed - 2 out of 5 local manufacturers failed Omeprazole Cap. - all 2 importers failed - 2 out of 13 local manufacturers failed Amoxycillin and Clavulanate Dry Syrup - 1 out of 4 importers failed

18. Discussion There are some limitation concerning the number of batches received of each brand product for analysis. Some products are released only 1 batch/year. Each product in the database does not represent the same amount of batches from each manufacturer. The pharmaceutical qualities of drug products from different manufacturers were compared for in vitro test in term of pass or fail to meet the standard specification.

19. Discussion (cont.) The results showed that problems regarding dissolution of tab or cap still remained for many drug products. The information is very important for product development of both imported and local manufacturers. Content uniformity is another important test item to demonstrate the uniformity of dosage unit, particularly low-dose drug products (eg. Colchicine tab )

20. Discussion (cont.) For Herbal products : which are very popular among health consumers and available in the marketplace. The results showed that there are problems regarding microbial contamination about 60% Failed, 33 out of 55 samples

21. Discussion (cont.) The poor quality products may be associated with manufacturers lack of GMP regarding –Humidity control –Formulation development –Stability study –Control of raw material storage condition packaging materialetc.

22. Conclusion The information of this study is helpful for : –Health care providers in making decision on product selection. –Improving drug procurement in a cost - effective manner. –Particularly in providing a better healthcare service to the patients.

23. Conclusion (cont.) The database created will be a source of information to all parties concerned in Ministry of Public Health for : –monitoring and/or planning the necessary action to be taken on the Essential Drug Program at the national level. –improving the national medical care scheme. –to effective regulatory enforcement of GMP measure.

24. Acknowledgement This study was supported by Department of Medical Sciences. The parties concerned in Ministry of Public Health.