TB medicines a Quality Assurance perspective

1. TB medicines a Quality Assurance perspective

2. Unit Objectives 1. Specify what is meant by quality assurance in managing the supply of tuberculosis medicines 2. Identify factors affecting pharmaceutical quality 3. Describe the components of a quality assurance system 4. Identify practical technical and managerial procedures to assure pharmaceutical quality 5. Identify resources for assistance in quality assurance activities

3. QA & QC 1. What is your definition of Quality Assurance? 2. What is Quality Control?

4. QA & QC Quality Assurance….. a constant awareness! Quality Control….. are specific actions you take!

5. QA & QC Power to the buyer !! Demand what YOU want/need! Accept only what you demanded!

6. Manufacturing: Medicine formulation Equipment and maintenance in factory Plant environment Manufacturing process Quality control Active ingredients Inactive ingredients Packaging of immediate and external containers Determinants of Pharmaceutical Product Quality (1)

7. Determinants of Pharmaceutical Product Quality (2) • Handling and storage conditions, (humidity, light, temperature, rain, dropping) • Shipment / transport • (Air) port handling • Transport to CMS • Storage conditions • Distribution within your health system

8. Product selection Supplier qualification for medicine selection Product certification Batch certification Contract specifications Inspection of shipments Laboratory testing Appropriate storage, transport, dispensing, and use procedures Product monitoring system Critical Elements of QA for Pharmaceutical Procurement

9. Actions to Obtain Good-Quality (TB) Products (1) • Careful Product Selection • Safe, effective, quality medicines as evidenced by clinical trials, reference literature • Dosage forms that have longer shelf life • Properly packaged products • Specify what YOU want!

10. Actions to Obtain Good-Quality (TB) Products (2) Careful Supplier Qualification for Selected Medicines • Select competitively by restricted tender, =prequalification • Request samples before purchase • Analyze information on supplier reliability and product quality • Select suppliers who can provide drug certifications • Verify quality of medicines with known bioavailability and stability problems by lab tests

11. Actions to Obtain Good-Quality Tuberculosis Products (3) • Bidding Document stipulate Specifications for Fixed-Dose Combinations • Comparative rifampicin bioavailability results equivalent to rifampicin single-drug standard methods • Comparative dissolution tests for all components • Declaration of consistency between the starting and subsequent batches • Specify what YOU want!

12. Actions to Obtain Good-Quality Tuberculosis Products (4) • Bidding Document Specifications for Fixed-Dose Combinations • Correlation over time between dissolution tests of different batches • Statement that raw materials are in accordance with reference specifications • Follow-up lab analysis data for each batch • Specify what YOU want/need!

13. 4-FDC (RHZE) R: molecular size & structure of API R: degrades in daylight R+H: interact (humidity!) HPLC peak of impurities can be hidden by R peak E: is highly hygroscopic: --- Coated tablets Dark coloured blisters, good quality alu foil. Too compact: ………. Disintegration & Dissolution! But High Quality 4-FDCs exist, if you insist!

14. Actions to Obtain Good-Quality (TB) Products (5) • Product Certification • Obtain (WHO-)GMP certificate from drug regulatory authority, PIC/s, ICH or other stringent regulatory authority • Obtain WHO-type certificates (CPP) from NDRA agency of exporting country

15. Actions to Obtain Good-Quality Products (6) • Batch Certificates • Obtain certificate of batch analysis from manufacturer or international quality control organization (for every batch!?) • Drug Regulatory Authorities • Verify registration of selected drugs

16. Actions to Obtain Good-Quality (TB) Products (7) • Contract Specifications • Pharmacopeia + year reference standard • Local language for product label • Minimum information to provide on label…….! • Any other additional information required • Standards for packaging to meet specific storage and transport conditions • Specify what YOU need/want!

17. Actions to verify the Quality of Shipped Medicines • Physical inspection of each shipment: • packing list / quantities, batch numbers, • Packing intact: stains, cracks or folds, pinholes in blisters, • Presentation of drugs: colour, smell etc • Laboratory testing: • standardized or random sampling • Pharmacopoeia • Sterility for injectables

18. Actions to Monitor Product Quality (1) Product problem reporting system indicates: — • Who should report quality problem • How to fill out reporting form, where to send, and to whom • Follow-up information to be provided • Criteria for retesting product

19. Actions to Monitor Product Quality (2) Product recall system allows quick response • Inventory system tracks batch to facility level, classifies type of recall, monitors the recall

20. Summary • If Quality Assurance for TB drugs or other medicines insufficient: (see worksheet hand-out) • Please make provision in your submission to GFAMT to improve the same. • Identify gaps, select items to address short term / medium term • Consider procuring from Quality Assured sources only: MSF, UNICEF, IDA, GLC, GDF

21. Management Challenge 1. Hand-out: 15 minutes to fill-out Include necessary actions in your PMS plan! 2. Sample Quality requirements in tender letter

22. Management Challenge Buyer Be AWARE!