WHO Prequalification – Medicines Finished Pharmaceutical Products

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

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 Shanghai CPHi ,June 2014

3. 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. 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

5. What requirements and standards do your products have to meet?

6. 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. Prequalification process Expression of Interest Product dossier + Site Master File Inspections Assessment Additional information and data Corrective actions Acceptable Compliance Prequalification Maintenance and monitoring

8. 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. 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. 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. http://www.who.int/prequal/

12. 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. Copenhagen training January 2012 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.

14. Prequalification activities FPP Prequalification API Prequalification API information 3.2.S APIMF Procedure PQ API EDQM CEP

15. Copenhagen training January 2012 Options for submitting API information • Technical requirementsfor 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

16. 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. Biopharmaceutics Classification System (BCS) Classification system for drug substances Aqueous solubility Intestinal permeability Drug substance classification according to BCS BCS-based Biowaiver

18. 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 products • http://apps.who.int/prequal/info_applicants/info_for_applicants_BE_implementation.htm

19. Pre-review of BE protocol Dr. Matthias Stahl stahlm@who.int or prequalassessment@who.int

20. How to Submit an application WHO Geneva: World Health OrganizationWHO Prequalification Team - MedicinesHIS/EMP/RHT  Room 61320 Avenue Appia1211 Geneva 27Switzerland UNICEF- Cophenhagen : CONFIDENTIALAttention: WHO Prequalification Team - MedicinesProduct Name:UNICEF Supply DivisionOceanvej 10 - 122150 Nordhavn Copenhagen Denmark

21. 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

22. Contact with PQP • Email to: prequalassessment@who.intprequalinspection@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. 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. Thank you for your attention!