1. WHO Prequalification – Medicines Finished Pharmaceutical Products Hua YIN yinh@who.int

2. Shanghai CPHi,June 2014 2 Outline Who can participate? What requirements and standards do your products have to meet to become prequalified? API options BE biowaivers How to submit an application ? Contact with WHO PQP

3. 3 Shanghai CPHi,June 2014 Who can participate? Therapeutic areas invited are: –HIV/AIDS –Malaria –Tuberculosis –Reproductive Health (RH) –Influenza –Acute diarrhoea in children (zinc) –Neglected Tropical Diseases (NTDs) EOIs containing list of invited products published on PQP web site

4. 4 Shanghai CPHi,June 2014 Who can participate? Only the products listed in the current EOIs are invited The strength, dosage forms should be the same as indicated in EOI EOIs are updated as per treatment requirement—PQ website Ask if you are not sure, prequalassessment@who.int prequalassessment@who.int

5. 5 Shanghai CPHi,June 2014 What requirements and standards do your products have to meet?

6. 6 Shanghai CPHi,June 2014 Prequalification of FPPs Assessment of Quality, Safety and Efficacy (Quality and BE) Inspection of manufacturing sites, FPP, API and CROs Monitoring of the products after prequalification (variations, requalification, inspections, random QC sampling, investigation of complaints)

7. 7 Shanghai CPHi,June 2014 Prequalification process Expression of Interest Acceptable Additional information and data Corrective actions Compliance Assessment Inspections Prequalification Maintenance and monitoring Product dossier + Site Master File

8. 8 Shanghai CPHi,June 2014 Quality Guidance WHO PQP guidelines are applied: –Guideline on submission of documentation for a multisource (generic) finished pharmaceutical product for the WHO Prequalification of Medicines Programme: Quality part –Specific guidance, e.g: Guidance for zinc products; magnesium sulfate injection; guidance on BE studies for RH medicines When WHO guidelines silence: ICH guidance If needed, other agencies' requirements, such as EMA, USFDA.

9. 9 Shanghai CPHi,June 2014 BE Guidance  WHO – Technical Report Series No. 937, May 2006 Annex 7: Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability Annex 8: Proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate release, solid oral dosage forms

10. 10 Shanghai CPHi,June 2014 Inspections (GMP) Inspection of FPP and API manufacturing sites, and CROs Inspections conducted by an SRA are taken into account when planning inspections The need for inspections of API sites and CROs are decided on a case by case risk basis. WHO GMP, GCP and GLP http://www.who.int/prequal/

11. 11 Shanghai CPHi,June 2014 http://www.who.int/prequal/

12. 12 Shanghai CPHi,June 2014 Documents to be submitted Covering letter Product dossier (Quality and Bioequivalent), in CTD format A product sample A site master file, for each manufacturing site In English

13. 13 Shanghai CPHi,June 2014 Options for submitting API information Option 1:Confirmation of API Prequalification document (CPQ); Option 2: Certificate of suitability of the European Pharmacopoeia (CEP); Option 3: Active pharmaceutical ingredient master file (APIMF) procedure; Option 4: Full API details in the product dossier. 13 C o p e n h ag e n tr ai ni n g Ja n u ar y 2 0 1 2

14. 14 Shanghai CPHi,June 2014 Prequalification activities FPP Prequalification API Prequalification API information PQ API EDQM CEP APIMF Procedure 3.2.S

15. 15 Shanghai CPHi,June 2014 Options for submitting API information Technical requirements for all options are same, the various processes ensure that ultimately all sections of the module 3.2.S are assessed. Documentation to be submitted in an FPP dossier are different for the four API options: CPQ < CEP < APIMF < Full information The four options for submitting API-related information also affects the manner in which API changes are handled after prequalification of the FPP—refer to PQP Variation guidance 15 C o p e n h ag e n tr ai ni n g Ja n u ar y 2 0 1 2

16. 16 Shanghai CPHi,June 2014 BE may not necessary Aqueous solutions –Intravenous solutions –Intramuscular, subcutaneous solutions –Oral solutions –Otic or ophthalmic solutions –Solutions for nasal administration Powders for reconstitution as solution

17. 17 Shanghai CPHi,June 2014 BCS-based Biowaiver PermeabilitySolubilityBCS Classification high BCS class I highlowBCS class II lowhighBCS class III low BCS class IV Biopharmaceutics Classification System (BCS) –Classification system for drug substances Aqueous solubility Intestinal permeability Drug substance classification according to BCS

18. 18 Shanghai CPHi,June 2014 BCS-based Biowaiver Requirements for BCS-based Biowaiver –General Notes on BCS-based Biowaiver Applications –Biowaiver Application Form: Biopharmaceutics Classification System (BCS) –BCS-based biowaiver applications for RH productsBCS-based biowaiver applications for RH products http://apps.who.int/prequal/info_applicants/info_for_applic ants_BE_implementation.htm

19. 19 Shanghai CPHi,June 2014 Pre-review of BE protocol Dr. Matthias Stahl stahlm@who.intstahlm@who.int or prequalassessment@who.intprequalassessment@who.int

20. 20 Shanghai CPHi,June 2014 How to Submit an application WHO Geneva: World Health Organization WHO Prequalification Team - Medicines HIS/EMP/RHT Room 613 20 Avenue Appia 1211 Geneva 27 Switzerland UNICEF- Cophenhagen : CONFIDENTIAL Attention: WHO Prequalification Team - Medicines Product Name: UNICEF Supply Division Oceanvej 10 - 12 2150 Nordhavn Copenhagen Denmark

21. 21 Shanghai CPHi,June 2014 How to Submit an application Step 1: Dossier CD/DVDs (API +FPP +BE) → Geneva After has been accepted for assessment and has been allocated a WHO reference number Step 2: Dossier (paper copies +CD/DVDs )+ samples → Copenhagen Site Master File & Contract Research Organization Master File (CROMF) (hard copies +CD/DVDs) → Geneva 21

22. 22 Shanghai CPHi,June 2014 Contact with PQP Email to: prequalassessment@who.int prequalinspection@who.intprequalassessment@who.int prequalinspection@who.int Technical Meetings with PQP assessors/inspectors –Pre-submission meeting –Any stage following submission –Teleconference, videoconference or face to face meeting –Meeting request form to be filled (PQ website)

23. 23 Abbreviations PQP: Prequalificaiton of Medicines Programme API: Active Pharmaceutical Ingredient FPP: Finished Pharmaceutical Product APIMF: Active Pharmaceutical Ingredient Master File (DMF) SRA: Stringent Regulatory Authorities CEP: Certificate of Suitability (CoS) QOS-PD: Quality Overall Summary - Product Dossier QIS: Quality Information Summary FDC: Fixed dose combination CTD: Common technical document BE: Bioequivalent BCS : Biopharmaceutics Classification System

24. 24 Shanghai CPHi,June 2014 Thank you for your attention!