Strengthening national drug regulatory capacity Valerio Reggi 11

Strengthening national drug regulatory capacity Valerio Reggi 11 October 2007 1 TBS Oct 2007 WHO - HTP

The three key statements on DRAs: n n n 2 TBS Oct 2007 health system counts on DRA for good, safe, and effective medicines, as well as fair rules and control on drug trade, information, and use any strategy to improve anything in the pharmaceutical area involves DRA any problem encountered in the pharmaceutical area has something to do with the DRA WHO - HTP

Drug regulation is a multi- faceted activity at the centre of complex interactions Manufacturers Products Government Regulatory authority Importers/Wholesalers/Retailers 3 TBS Oct 2007 Experts Prescribers Medicines Patients/Consumers WHO - HTP

Drug regulation is a multi- faceted activity at the centre of complex interactions Manufacturers Products Government Regulatory authority Importers/Wholesalers/Retailers 4 TBS Oct 2007 Experts Prescribers Medicines Patients/Consumers WHO - HTP

Drug regulation is a multi- faceted activity at the centre of complex interactions Manufacturers Products Government Regulatory authority Importers/Wholesalers/Retailers 5 TBS Oct 2007 Experts Prescribers Medicines Patients/Consumers WHO - HTP

Drug regulation is a multi- faceted activity at the centre of complex interactions Manufacturers Products Government Regulatory authority Importers/Wholesalers/Retailers 6 TBS Oct 2007 Experts Prescribers Medicines Patients/Consumers WHO - HTP

Drug regulation comprises all the legal, administrative & technical arrangements meant to ensure that: n n 7 TBS Oct 2007 all premises, persons & practices engaged in the development, manufacture, importation, exportation, wholesale, supply, dispensing & promotion of drugs comply with approved standards, norms, procedures and requirements drug products are safe, effective and of acceptable quality product information is unbiased, accurate and appropriate drugs are available WHO - HTP

What is quality? 8 TBS Oct 2007 WHO - HTP

Background • 2000, Nepal: school children mass-treatment campaign • Locally procured albendazole • QC tested after treatment completed, result: failed • Campaign outcome: success 9 TBS Oct 2007 WHO - HTP

Questions Wrong sample? Wrong test? Wrong results? children? Wrong worms? Wrong 10 TBS Oct 2007 WHO - HTP

Answer 11 TBS Oct 2007 WHO - HTP

The study Two locally-manufactured generic albendazole (ABZ) products (Curex and Royal Drug) used for de-worming children in Nepal since 1999 tested against originator product (Glaxo. Smith. Kline-GSK). API content, disintegration and dissolution testing and a randomised controlled clinical trial comparing cure rates (CR) and egg reduction rates (ERR) for Ascaris lumbricoides, Trichuris trichiura and hookworm infections 1277 children examined before and 21 days after treatment 12 TBS Oct 2007 WHO - HTP

Results Drug Albendazole 400 mg Batch N Quantity (mg/tablet) % Active Ingredient Disintegration time (minutes) % Dissolution Zentel 400 (GSK) 48907 G 10 0 397. 6 (USP) 394. 5 (IP) 99. 2 (USP) 98. 7 (IP) 6. 7 (IP) 84. 8 (USP) Passed RDZ-400 (Royal Drug Ltd Nepal) T-53 401. 3 (USP) 394. 0 (IP) 100. 4 (USP) 98. 7 (IP) 11. 8 (IP) 10. 3 (USP) Failed Azol 400 (Curex Ltd Nepal) 61 413. 8 (USP) 415. 8 (IP) 103. 5 (USP) 103. 9 (IP) > 1 hour (IP) 0. 27 (USP) Failed 13 TBS Oct 2007 Dissolution WHO - HTP

Results Drug Albendazole 400 mg Ascaris Trichuris Hookworms 14 TBS Oct 2007 N Day 0 % Pos EPG a Day 21 % Pos EPG CR ERR (95%CI) GSK 429 31. 5 13 0. 9 0. 0 97. 0 92. 6 (89. 2, 95. 0) Royal Drug 419 33. 9 17 1. 7 0. 1 95. 0 93. 8 (90. 9, 95. 8) Curex 429 36. 1 19 6. 3 0. 6 82. 6 b c 91. 9 (88. 0, 94. 4) GSK 429 80. 7 79 62. 2 22 28. 6 71. 7 (64. 4, 77. 5) Royal Drug 419 80. 0 75 61. 6 21 26. 6 71. 4 (64. 6, 77. 1) Curex 429 78. 3 60 60. 6 21 28. 0 63. 2 (53. 7, 70. 8) d e GSK 429 49. 0 13 14. 2 0. 9 74. 3 87. 1 (83. 3, 90. 1) Royal Drug 419 50. 1 15 24. 6 2. 0 53. 3 b 80. 8 (75. 6, 84. 9) d Curex 429 47. 8 12 25. 9 2. 4 50. 7 b 73. 1 (66. 2, 78. 6) b c WHO - HTP

Results • goal of mass treatment campaigns is to reduce the overall burden of infection within a population • 6. 8 million tablets of ABZ are procured every year in Nepal COST (US$) 15 TBS Oct 2007 Extra COST Curex 81, 600 Royal Drug 115, 600 34, 000 GSK 136, 000 54, 400 WHO - HTP

Results … questions on the importance of certain criteria used for planning mass treatment campaigns with anthelminthic drugs. The extremely poor performance of Curex's ABZ in quality tests would lead to the conclusion that it is unsuitable for use in a campaign. Yet, it has shown a good degree of effectiveness that, although inferior to the other two drugs, challenges the relevance or reliability of quality testing, as currently done, as a major decision criterion for inclusion of a specific product in de-worming campaigns. 16 TBS Oct 2007 WHO - HTP

What is quality? Quality is suitability for purpose! All three products are of acceptable quality then? Let's discuss 17 TBS Oct 2007 WHO - HTP