who prequalification – medicines finished pharmaceutical products

WHO Prequalification – Medicines Finished Pharmaceutical Products

Hua [email protected]

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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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

[email protected] or [email protected]

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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!