Quality Assurance Processes for TB Drugs

1. Quality Assurance Processes for TB Drugs

2. GDF Quality Assurance Processes

3. The products GDF procures are subject to the following Quality Assurance criteria: • Manufacturers' compliance with WHO/GMP standards as assessed under the TB Prequalification Project. GMP

4. Product compliance with either: • Option (I): WHO-recommended standards for medicines as assessed under the aforementioned WHO/PSM Procurement, Quality and Sourcing Project: Access to Anti-Tuberculosis Drugs of Acceptable Quality i.e. Product is Prequalified Product Compliance: Option I

5. Option (II): compliance with the assessment criteria as determined by WHO/PSM & product dossiers are assessed against these criteria by an ad hoc transparent, independent expert committee convened by WHO/PSM at the request of GDF. • The ad hoc committee is drawn from the same team of evaluators who assess product dossiers for quality aspects and for efficacy and safety (or bio-equivalence) under the TB Prequalification Project. • Where a product which complies with Option I has at least 3 manufacturers whocomply with GDF tender criteriaGDF limits procurement of that product to those manufacturers. Product Compliance: Option II

6. All batches of all products procured by GDF, irrespective of whether product compliance falls under option I or option II, are subject to independent quality control testing by a laboratory that: • (a) is from a country that is a member of the Pharmaceutical Inspection Cooperation Scheme (PIC/S) • (b) from a country that is party to the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) or • (c) has been assessed by WHO PSM/QSM and found to meet recommended international norms and standards for the analysis of products Quality Control

7. GDF adheres to GFATM compliance list where products are included there • GDF adheres to its own QA criteria where product is not on GFATM compliance list • After next GDF tender in Q2/Q3, for GDF QA criteria GDF will limit procurement to suppliers under Option I where there 2 or more suppliers under this option Implications for GFATM PRs

8. For more information on TB Prequalification, please refer to the Global Drug Facility web-site: www.stoptb.org/GDF or the WHO website at www.who.int /medicines Or contact, via electronic mail: GDF.PRS@stoptb.org doucelinc@who.int griffing@who.int Contact Information

9. General QA Information for TB

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

11. 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 Actions to Obtain Good-Quality (TB) Products (2)

12. 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 Actions to Obtain Good-Quality Tuberculosis Products (3)

13. 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 Actions to Obtain Good-Quality Tuberculosis Products (4)

14. Product Certification • Obtain GMP certificate from drug regulatory authority, UNIPAC, or other international agency • Obtain WHO-type certificate from drug control agency of exporting country Actions to Obtain Good-Quality (TB) Products (5)

15. 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 • Request GMP or WHO-type certificates for imported drugs Actions to Obtain Good-Quality Products (6)

16. Contract Specifications • Pharmacopeia 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 Actions to Obtain Good-Quality (TB) Products (7)

17. Physical inspection of each shipment: • packing list / quantities, batch numbers, • Packing intact • Presentation of drugs: color, smell etc • Shelf life • Laboratory testing: • standardized or random sampling • Pharmacopoeia • Sterility for injectables Actions to Verify the Quality of Shipped Medicines

18. 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 Actions to Monitor Product Quality (1)

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

20. Please make provision in proposals to GFATM or reprogramming of approved proposals to improve quality assurance: • Identify gaps, select items to address short term / medium term • Ensure PRs adhere to GFATM compliance list • In general advise procurement from Quality Assured sources only: • WHO List, GDF, GLC, GFATM List, MSF, UNICEF, IDA Summary