The WHO Prequalification of Medicines Programme Dossier Assessment Update

1. The WHO Prequalification of Medicines ProgrammeDossier Assessment Update Rutendo Kuwana Technical Officer Prequalification of Medicines Program WHO

2. 5 Key Assessment Stages EMP TBS, 3 November 2011

3. Invitation for Expression of interest (EOI) • A list of medicines invited for prequalification • Priority public health medicines • We can only accept product dossiers for medicines included in this list • List prepared by WHO clinical experts (HIV, TB, Malaria, RH, Influenza, Zinc, NTD) • Based on inclusion in treatment guidelines and/or WHO model list of essential medicines • Revised as needed to capture new developments EMP TBS, 3 November 2011

4. Expressions of Interest Currently 8 EoIs • Active Pharmaceutical Ingredients (API) – 2nd • HIV/AIDS – 10th • Influenza – 2nd • Malaria – 9th • Neglected Tropical Diseases (NTD) – 1st • Reproductive Health – 5th • Tuberculosis – 10th • Diarrhoea (Zinc) – 1st EMP TBS, 3 November 2011

5. Paths for inclusion of a product in the list of prequalified products • Prequalification of multisource generic products • Full review and inspection by PQP • Prequalification of innovators • Approval based on marketing authorization issued by an NMRA in ICH region and associated countries • Prequalification of generic products approved by SRA • Approval based on SRA marketing authorization • For established generic products • Recognition of temporary approvals / scientific opinions • USFDA PEPFAR approval/tentative approval • EMA article 58 • Health Canada Access programme EMP TBS, 3 November 2011

6. Screening • Review data in the Application Form and Dossier • Mainly qualitative review i.e. is the data there or not • Some selected quantitative assessments done e.g. completeness of formulation tables, duration of studies • Administrative and Technical Completeness EMP TBS, 3 November 2011

7. Product dossiers accepted for assessment: 2005 – 2011 (as at 1st November 2011) 20052006200720082009 20102011 HIV 67 42 25 42 24 21* 26(19) TB 17 9 17 12 11 16 17 (11) Malaria 3 5 7 9 3 6 8 (5) Repr Health - - 10 4 7 7 3 (0) Influenza - - - 1 7 0 0 (0) Diarrhoea - - - - 1 1 2 (1) NTD - - - - - - 1(1) Total Accptd 87 56 59 68 53 35 37 Total Submitted 90 92 83 51 57 * Includes 2 products (Water for Injection) not included in any of the EoIs (…) dossiers accepted for assessment EMP TBS, 3 November 2011

8. Administration of assessments • Coordinator with a team of, • Quality assessors • BE assessors • Clinical assessors • Six full time (in-house) • More than 50 temporary advisors (pool of external assessors) • Six sessions per annum (every other month) in CPH. Details of meeting dates published on website • More than 30 assessors per session. EMP TBS, 3 November 2011

9. 2005 – 2011 Prequalification Stats EMP TBS, 3 November 2011

10. International standards for prequalification • Primarily WHO guidance documents and standards • PQ main generic and variation guidelines • The WHO Bioequivalence and bio waiver guidelines • The WHO Stability guideline • International Pharmacopoeia • WHO GMP and GCP Guidelines • ICH guidelines • Other guides issued by SRAs such as USFDA and EMA • Other recognized pharmacopoeias • BP, EP, JP, USP EMP TBS, 3 November 2011

11. New guidelines EMP TBS, 3 November 2011 “Preparation” guideline: 10.375: Guideline on submission of documentation for a multisource (generic) finished pharmaceutical product (FPP): Preparation of product dossiers (PDs) in Common Technical Document (CTD) Format; “Quality” guideline: 10.373: Guideline on submission of documentation for a multisource (generic) finished pharmaceutical product (FPP): Quality part

12. Key changes from the previous guideline EMP TBS, 3 November 2011 Reductions in requirements: - fewer batches required to establish the FPP shelf-life - process validation report for pilot batches no longer required (replaced by uniformity demonstration for the biolot) - reduced process validation/pharmaceutical development requirements for “established” generics

13. Application of BCS in PQP • PQP has reviewed existing information on the bioavailability and dissolution data of the invited medicines • Identified some drug substances as eligible for a BCS-based biowaiver application - either monocomponent or fixed-dose combination (FDC) products • Monocomponent or FDC products containing other drug substances must be supported with in vivo BE data EMP TBS, 3 November 2011

14. PQ Dossier Variation Guidance Three main categories of variations, according to potential impact to quality of product and current timelines we aim to achieve (achieved already) • Notification - no or minimal impact: 30 days • Minor change - potential minor impact: 60 days • Major change - potential major impact: 60 days EMP TBS, 3 November 2011

15. Requalification Procedure for prequalification of pharmaceutical products requires holders of WHO-prequalified products to submit a quality review after five years from the date of prequalification of the product, or when requested to do so by PQP (whichever date is earlier) EMP TBS, 3 November 2011

16. Status of RQ Applications – Oct 2011 EMP TBS, 3 November 2011

17. Current Affairs • Revision of the Variation Guidelines • Published list of prequalified APIs and their specific attributes (5) • Part 2(b) of WHOPAR including pictures of product • Part 8 of WHOPAR – variations now included • Publish prevailing timelines for key processes • New internal centralised and enhanced database • Information to applicants on how we prioritise assessments and inspections • BCS biowaiver – to include Emtricitabine and Abacavir EMP TBS, 3 November 2011