Structure of Dossier of Medicinal Product- Q part Gabriel K. Kaddu Head, Drug Assessment and Registration National Drug Authority Training workshop: Training

Structure of Dossier of Medicinal Product- Q part

Gabriel K. Kaddu

Head, Drug Assessment and Registration

National Drug Authority

Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda.

Artemisinin based combined medicinesFebruary 23-27, 2009, Kampala, Uganda 2 |

Structure of Dossier of Medicinal product Q part

Structure of Dossier of Medicinal product Q part

Outline of presentation

Objective of the presentation

The Common Technical Document (CTD) for the Registration of Pharmaceuticals for Human Use: Quality – M4Q MODULE 3: QUALITY

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


Overview of Dossier Requirements and Guidelines

Overview of Dossier Requirements and Guidelines

Objective of the presentation:– To provide an overview of the dossier requirements and

Guidelines used or referenced under the WHO Prequalification Program

– To demonstrate how the requirements and guidelines can be applied or used as reference.


Overview of Dossier Requirements and Guidelines (1)


Common Technical Document

(CTD)

An initiative under the ICH: Europe, Japan and USA.

http://www.ich.org


Structure of dossier of medicinal products, information on the CTD format (1)

Structure of dossier of medicinal products, information on the CTD format (1)

A common format for the technical documentation:– significantly reduces the time and resources needed to compile

applications for registration of human pharmaceuticals– eases the preparation of electronic submissions– Facilitates regulatory reviews and communication with the

applicant by a standard document of common elements– Simplifies exchange of regulatory information between

Regulatory Authorities

This guideline is not intended to indicate what studies are required. It merely indicates an appropriate format for the data that have been acquired.


CTD format (2)CTD format (2)

GENERAL PRINCIPLES – Text and tables should be prepared using margins that allow the document

to be printed on A4 paper.– The left-hand margin should be sufficiently large that information is not

obscured by the method of binding.– Font sizes for text and tables should be easily legible, even after

photocopying. Times New Roman, 12-point font, is recommended for narrative text.

– Every page should be numbered.– Acronyms and abbreviations should be defined the first time they are used

in each module.– References should be cited in accordance with the current edition of the

Uniform Requirements for Manuscripts Submitted to Biomedical Journals, International Committee of Medical Journal Editors (ICMJE)1.



The CTD is organized into five modules:– Module 1 is region specific.– Modules 2, 3, 4, and 5 are intended to be common for all regions.

Module 1. Administrative Information and Prescribing Information

– Should contain documents specific to each region; e.g. application forms or the proposed label for use in the region. The content and format of this module can be specified by the relevant regulatory authorities.

Module 1: Administrative Information and Prescribing Information – 1.1 Table of Contents of the Submission Including Module 1 – 1.2 Documents Specific to Each Region (for example, application forms,

prescribing information)



Module 2. Common Technical Document Summaries – Should begin with a general introduction to the pharmaceutical, including its pharmacological class, mode of

action, and proposed clinical use. In general, the Introduction should not exceed one page.– Should contain 7 sections in the following order :

• 2.1 Common Technical Document Table of Contents (Modules 2-5) • 2.2 CTD Introduction • 2.3 Quality Overall Summary • 2.4 Non-clinical Overview • 2.5 Clinical Overview • 2.6 Non-clinical Written and Tabulated Summaries

– Pharmacology – Pharmacokinetics – Toxicology

• 2.7 Clinical Summary – Biopharmaceutical Studies and Associated Analytical Methods – Clinical Pharmacology Studies – Clinical Efficacy – Clinical Safety – Literature References – Synopses of Individual Studies



Module 3. Quality – Information on Quality should be presented in the structured

format described in Guideline M4Q.

Module 3: Quality – 3.1 Table of Contents of Module 3 – 3.2 Body of Data

– 3.3 Literature References


CTD format: Numbering System: Module 3CTD format: Numbering System: Module 3Module 3

3.1 MODULE 3 TABLE OF CONTENTS

3.2 BODY OF DATA

3.2.S DRUG SUBSTANCE

3.2.S.1 General Information

3.2.S.2 Manufacture

3.2.S.3 Characterisation

3.2.S.4 Control of Drug Substance

3.2.S.5 Reference Standards or Materials

3.2.S.6 Container Closure System

3.2.S.7 Stability

3.2.P DRUG PRODUCT

3.2.P.1 Description and Composition of the Drug Product

3.2.P.2 Pharmaceutical Development

3.2.P.3 Manufacture

3.2.P.4 Control of Excipients 3.2.P.5 Control of Drug Product 3.2.P.6 Reference Standards or Materials 3.2.P.7 Container Closure System 3.2.P.8 Stability

Module 3 (Cont.)

3.2.A APPENDICES

3.2.A.1 Facilities and Equipment

3.2.A.2 Adventitious Agents Safety Evaluation

3.2.A.3 Novel Excipients

3.2.R REGIONAL INFORMATION

3.3 LITERATURE REFERENCES




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

http://mednet3.who.int/prequal


Generic Guide: Documentation on Quality Part to be submitted to the WHO PQ teamGeneric Guide: Documentation on Quality Part to be submitted to the WHO PQ team

Covering letter

Product dossier on Quality part

PQIF (annex 8 to the main generic guide): properly filled out in WinWord format, www.who.int/prequal/


Generic Guide: Quality dossier / Section 1Generic Guide: Quality dossier / Section 1

Information on the Finished Pharmaceutical Product (FPP)

1.1. Details of the Product- Name, dosage form and strength of the product- Approved generic name (INN)- Visual description of the FPP- Visual description of the packaging

1.2. Samples (visual examination and comparison with the SPC and PIL

1.3. Regulatory situation in Member States / list countries- Countries where a MA has been issued- Countries where a MA has been withdrawn- Countries where a Marketing Application has been rejected, deferred


Generic Guide:Generic Guide:

Quality dossier / Section 2

Active Pharmaceutical Ingredient (API)


Generic Guide: Quality/Section 2: APIGeneric Guide: Quality/Section 2: API

Scientific data on the API can be submitted in the following order of preference

A valid Certificate of Suitability (CoS) or CEP, latest version, with all its annexes issued by EDQM

An APIMF (Active Pharmaceutical Ingredient Master File) submitted by the API manufacturer, containing the whole information requested in section 2

Complete submission of data requested in Section 2


Generic Guide: Quality/Section 2: APIComplete submission option

Generic Guide: Quality/Section 2: APIComplete submission option

2.1. Nomenclature (INN, chemical name, CAS No.)

2.2. Properties of the API**

2.3. Site(s) of manufacture

2.4. Route(s) of synthesis**

2.5. Specifications**

2.6. Container- closure system

2.7. Stability testing

** The requirements may differ depending on if the API is pharmacopoeial or non-pharmacopoeial


Generic Guide: Quality/Section 2: API, Certification of Suitability (CoS) / CEP Option

Generic Guide: Quality/Section 2: API, Certification of Suitability (CoS) / CEP Option Issued by EDQM for substances described in the Ph. Eur. www.edqm.eu

2 types of CEPs: quality CEP and TSE CEP

Information which can be found on a quality CEP CEP reference, CEP holder, site of manufacture of the substance, monograph according to which the dossier is evaluated, additional impurities and residual solvents not mentioned in the monograph, additional methods to those of the monograph are appended, re-test period with packaging system and storage condition (if applicable), date of validity of the CEP

A quality CEP certifies that the quality of the substance can be checked according to the Ph. Eur. by applying the analytical methods described in the Ph. Eur. monograph supplemented by those

appended to the CEP.


Generic Guide: Quality/Section 2: API, APIMF Option

Generic Guide: Quality/Section 2: API, APIMF Option

Procedure implemented since January 2007, www.who.int/prequal

To protect the "know-how" of the manufacturer of the API – While giving the whole information on manufacture of the API to the

WHO PQ team of assessors– While giving a part of the information to the applicant to

Prequalification/ manufacturer of the finished product

An APIMF is composed of: Applicant's /Open part + Restricted / Closed part

Manufacturer of the API should make available to the applicant to Prequalification the Applicant's part + Letter of access


Generic Guide: Quality/Section 2: API. APIMF Option

Generic Guide: Quality/Section 2: API. APIMF Option

Manufacturer of the API should submit on the other hand the Applicant's part + Restricted + Letter of access to WHO team An APIMF is to be submitted only in support of a FPP dossier

An APIMF is not an independent dossier of API

Scope open to pharmacopoeial and non-pharmacopoeial APIs

Scope of APIMF only open to APIs

See annex 1 of the APIMF guide for the content of an APIMF

Content of APIMF corresponds to data required in section 2 of the prequalification quality dossier without difference between pharmacopoeial and non-pharmacopoeial APIs


Generic Guide:Generic Guide:

Quality dossier / Section 3

Finished Pharmaceutical Product

(FPP)


Generic Guide: Quality/Section 3: FPPGeneric Guide: Quality/Section 3: FPP

3.1. Manufacturing and marketing authorization

3.2. Pharmaceutical development

3.3. Formulation

3.4. Sites of manufacture

3.5. Manufacturing process

3.6. Manufacturing process controls of Critical steps and intermediates

3.7. Process validation and Evaluation

3.8. Specifications for excipients

3.9. Control of the FPP

3.10. Container/closure system (s) and other packaging

3.11. Stability testing


Generic Guide: Quality/Section 3: FPPGeneric Guide: Quality/Section 3: FPP

3.12. Container labelling

3.13. Product information for health professionals

3.14. Patient information and package leaflet

3.15. Justification for any differences to the product in the country or countries issuing the submitted WHO-type certificate(s)


THANK YOU