WHO Prequalification – Medicines Finished Pharmaceutical Products
Shanghai CPHi ,June 20142
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
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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
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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, [email protected]
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What requirements and standards do your products have to meet?
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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)
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Prequalification process
Expression of Interest
Acceptable
Additional informationand data
Corrective actions
Compliance
Assessment Inspections
Prequalification
Maintenance and monitoring
Product dossier+ Site Master File
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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.
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BE GuidanceBE 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
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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/
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http://www.who.int/prequal/
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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
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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.
13Copenhagen trainingJanuary 2012
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Prequalification activities
FPP Prequalification API Prequalification
API information
PQ API EDQM
CEP APIMF
Procedure3.2.S
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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
15Copenhagen trainingJanuary 2012
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BE may not necessaryBE 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
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BCS-based BiowaiverBCS-based Biowaiver
BCS Classification Solubility Permeability
BCS class I high high
BCS class II low high
BCS class III high low
BCS class IV low low
• Biopharmaceutics Classification System (BCS)– Classification system for drug substances
• Aqueous solubility• Intestinal permeability
• Drug substance classification according to BCS
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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
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Pre-review of BE protocol
Dr. Matthias Stahl
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How to Submit an application
WHO Geneva: World Health OrganizationWHO Prequalification Team - MedicinesHIS/EMP/RHT Room 61320 Avenue Appia1211 Geneva 27Switzerland
UNICEF- Cophenhagen : CONFIDENTIAL
Attention: WHO Prequalification Team - MedicinesProduct Name:UNICEF Supply DivisionOceanvej 10 - 122150 Nordhavn Copenhagen Denmark
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How to Submit an application
Step 1: Dossier CD/DVDs (API +FPP +BE) → GenevaAfter 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
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Contact with PQP
• Email to: [email protected] [email protected]
• 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)
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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
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Thank you for your attention!