1 TBS Oct 2007 WHO - HTP

Strengthening national drug regulatory capacity

Valerio Reggi11 October 2007

2 TBS Oct 2007 WHO - HTP

The three key statements on DRAs:

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

3 TBS Oct 2007 WHO - HTP

Drug regulation is a multi- faceted activity at the centre of complex interactions

Regulatory authority

Manufacturers

Prescribers

Importers/Wholesalers/Retailers

Patients/Consumers

Products

ExpertsGovernment

Medicines

4 TBS Oct 2007 WHO - HTP

Drug regulation is a multi- faceted activity at the centre of complex interactions

Regulatory authority

Manufacturers

Prescribers

Importers/Wholesalers/Retailers

Patients/Consumers

Products

ExpertsGovernment

Medicines

5 TBS Oct 2007 WHO - HTP

Drug regulation is a multi- faceted activity at the centre of complex interactions

Regulatory authority

Manufacturers

Prescribers

Importers/Wholesalers/Retailers

Patients/Consumers

Products

ExpertsGovernment

Medicines

6 TBS Oct 2007 WHO - HTP

Drug regulation is a multi- faceted activity at the centre of complex interactions

Regulatory authority

Manufacturers

Prescribers

Importers/Wholesalers/Retailers

Patients/Consumers

Products

ExpertsGovernment

Medicines

7 TBS Oct 2007 WHO - HTP

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

Drug regulation comprises all the legal, administrative & technical arrangements meant to ensure that:

8 TBS Oct 2007 WHO - HTP

What is quality?

9 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

10 TBS Oct 2007 WHO - HTP

Wrong sample?

Wrong results?

Wrong test?

Wrong children?

Wrong worms?

Questions

11 TBS Oct 2007 WHO - HTP

Answer

12 TBS Oct 2007 WHO - HTP

The studyTwo locally-manufactured generic albendazole (ABZ)

products (Curex and Royal Drug) used for de-worming children in Nepal since 1999

tested against originator product (GlaxoSmithKline-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

13 TBS Oct 2007 WHO - HTP

Results

DrugAlbendazole 400 mg

Batch N Quantity (mg/tablet)

% Active Ingredient

Disintegration time (minutes)

% Dissolution

Dissolution

Zentel 400(GSK)

48907G100

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

14 TBS Oct 2007 WHO - HTP

ResultsDrugAlbendazole 400 mg

N Day 0% Pos EPG a

Day 21% Pos EPG

CR ERR (95%CI)

Ascaris 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)

Trichuris 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

Hookworms 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

15 TBS Oct 2007 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

Curex 81,600

Royal Drug 115,600 34,000

GSK 136,000 54,400

COST (US$) Extra COST

16 TBS Oct 2007 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.

17 TBS Oct 2007 WHO - HTP

What is quality?Quality is suitability for purpose!

All three products are of acceptable quality then?

Let's discuss