1 tg dekker – who, ukraineoctober 2005 introduction to dossier requirements and guidelines within...

1 TG Dekker – WHO, UkraineOctober 2005

Introduction to Dossier Requirements and Guidelines within the

Prequalification Project (quality part)

World Health OrganizationTraining Workshop on Pharmaceutical

Quality, GMP and BioequivalenceKiev - Ukraine

3 to 7 October 2005

Theo Dekker, D.Sc., consultant to WHOResearch Institute for Industrial Pharmacy

North-West University, Potchefstroom, South [email protected]


Some abbreviations used in all presentationsAPI Active pharmaceutical ingredientBP British PharmacopoeiaCEP EU certificate of suitabilityCPP WHO-type Certificate of a Pharmaceutical Product EOI Expression of interestFDC Fixed-dose combinationFPP Finished pharmaceutical productICH International Conference on HarmonizationInt.Ph. International PharmacopoeiaIR InfraredPh.Eur. European PharmacopoeiaSmPC Summary of product characteristicsTB TuberculosisUSP United States PharmacopeiaXRPD X-ray powder diffractogram


Prequalification website http://mednet3.who.int/prequal/


PQ Website – menu

Bio group

GMP group

publication on QC testing Jan 06


PQ Website – product dossiers

Frequently asked questions Which products do we prequalify? What data and information needs to be submitted in a

dossier for a generic product? What data and information needs to be submitted in a

dossier for an innovator product? What does a manufacturer have to submit to prove

efficacy of a multi-source generic product? How often are dossiers assessed?

Click on question to get to answer


PQ Website – menu

Bio group

GMP group


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Guidelines for submission (from web)

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2


Guideline (“Main”)FPPs not approved by ICH/associated DRA

Guideline on Submission of Documentationfor Prequalification of Multisource (Generic) Finished Pharmaceutical Products (FPPs)

used in the Treatment of HIV/AIDS, Malaria and Tuberculosis (“main guideline”, hand-out)

Based onMarketing Authorization of Pharmaceutical

Products with special Reference to Multisource (Generic) Products: a Manual for a Drug

Regulatory Authority(WHO Blue Book, current edition)


Multisource products: Blue Book

Multisource products are pharmaceutically equivalent

Pharmaceutically equivalent products Contain the same API(s)

• in the same amount(s) • in the same dosage form

Meet similar quality standards Are intended for the same route of administration

Multisource products that are therapeutically equivalent are interchangeable


Main guidelineAdministrative 1/50

A: Covering letter by responsible person Statement: information is true and correct

B: Application (Product dossier) Four main sections (with subsections) Keep to the sections/subsections as prescribed Sections/subsections should be clearly marked

• preferably with securely fixed tags

Number all pages (essential) Table of contents

• List sections, subsections – with page numbers


Main GuidelineDossier requirements – main sections

Section 1 Characteristics of the FPP (3/50)

Section 2Active Pharmaceutical Ingredients (APIs) (4/50)

Section 3Finished Pharmaceutical Products (FPPs) (10/50)

Section 4Interchangeability (Bioequivalence) (25/50)


Main guidelineAnnexes

Annex 1: Model Certificate of a Pharmaceutical Product 27/50

Annex 2: Model Batch Certificate of a Pharmaceutical Product 31/50

Annex 3: Model Stability Report of Active Pharmaceutical Ingredient (API) 33/50

Annex 4: Model Stability Report of Capsules/Tablets 36/50

Annex 5: Suggested Structure of the Summary of Product Characteristics (SmPC) 40/50

Annex 6: Suggested structure of the Package Information Leaflet (PIL) 43/50

Annex 7: Recommended presentation of bioequivalence trial information 45/50


Main guideline: Supplements

Supplement 1Guideline on Submission of Documentation for

Prequalification of Multi-source (Generic) Finished Pharmaceutical Products (FPPs)

Used in the Treatment of HIV/AIDS, Malaria and Tuberculosis

Dissolution Testing

for use from July 2005 (CPH25)


Main guideline: Supplements

Supplement 2

Guideline on Submission of Documentation for Prequalification of Multi-source (Generic) Finished Pharmaceutical Products (FPPs)

Used in the Treatment of HIV/AIDS, Malaria and Tuberculosis

Extension of the WHO List of Stable(not easily degradable ARV) APIs

(for stability testing)

for use from July 2005 (CPH25)


GuidelineFPPs approved by ICH & associated DRAs

Guide on Submission of Documentation for Prequalification of Finished Pharmaceutical Products (FPPs) used in the treatment of HIV/AIDS, malaria and tuberculosis and approved by Drug Regulatory Authorities (DRAs) in the International Conference on

Harmonization (ICH) region and associated countries, including inter alia the EU, Japan

and USA


PQ Website – menu

Bio group

GMP group


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Guidelines: FDCsFixed-Dose Combinations (FDCs)

Draft guidelines for registration of fixed-dose combination medicinal products

(WHO, 2005)comprehensive on all aspects of safety, efficacy and quality

Scientific and Technical Principles for Fixed Dose Combination Drug Products for Treatment of HIV/AIDS, Malaria, and

Tuberculosis(HHS, UNAIDS, WHO & SADC, 2004)

(“Botswana Principles”)


ICH guidelines

ICH guidelines are used when a quality aspect cannot be (fully) assessed by the WHO guidelines, for instance: Q3A(R). Impurities in new drug substances Q3B(R). Impurities in new drug products Q3C. Impurities: Guideline for residual solvents Q6A. Specifications: Test procedures and

acceptance criteria for new drug substances and new drug products: chemical substances (with decision trees)


Prequalification projectVariation Guideline

To be published soon on PQ website The prequalification process is dynamic, taking

into account that changes to the original dossier may become necessary during the lifetime of the product

Any changes or variations may involve administrative and/or more substantial changes and are subject to approval within the prequalification program


Prequalification projectVariation Guideline (2)

ANNEX I List of minor changes

• The conditions which must apply is stipulated• The relevant part of the dossier to be resubmitted or

updated, with the documentation required, is listed

ANNEX II Lists major changes in general

ANNEX III Lists types of changes which may require a

new application


Closing remarks

1. The dossier submitted must conform to the requirements set out in the current WHO guidelines, as posted on web

2. The assessment of quality and safety/efficacy data presented is based on the current WHO guidelines

3. ICH guidelines are used when a quality aspect cannot be assessed by the WHO guidelines

4. The quality assessment includes variations or changes to already prequalified products

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