Transcript Guidelines - World Health Organization

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.
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 Multisource (Generic) Finished Pharmaceutical Products (FPPs) Used in the
Treatment of HIV/AIDs, Malaria and Tuberculosis
2|
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
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.
3|
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Overview of Dossier Requirements and
Guidelines (1)
Common Technical Document
(CTD)
An initiative under the ICH: Europe, Japan and
USA.
http://www.ich.org
4|
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
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.
5|
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
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.
6|
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
CTD format (3)
 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)
7|
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
CTD format (4)

Module 2. Common Technical Document Summaries
–
–
8|
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
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
CTD format (5)
 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
9|
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
CTD format: Numbering System: Module 3
Module 3
3.1
3.2
3.2.S
3.2.S.1
3.2.S.2
3.2.S.3
3.2.S.4
3.2.S.5
3.2.S.6
3.2.S.7
3.2.P
3.2.P.1
MODULE 3 TABLE OF CONTENTS
BODY OF DATA
DRUG SUBSTANCE
General Information
Manufacture
Characterisation
Control of Drug Substance
Reference Standards or Materials
Container Closure System
Stability
DRUG PRODUCT
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.7Artemisinin
Container
based Closure
combinedSystem
medicines
| February 23-27, 2009, Kampala, Uganda
10
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
Overview of Dossier Requirements and
Guidelines (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
 http://mednet3.who.int/prequal
11 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Generic 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/
12 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Generic 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
13 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Generic Guide:
 Quality dossier / Section 2
Active Pharmaceutical Ingredient (API)
14 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Generic 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
15 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Generic Guide: Quality/Section 2: API
Complete 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
16 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
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.
17 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
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
18 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
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
19 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Generic Guide:
Quality dossier / Section 3
Finished Pharmaceutical Product
(FPP)
20 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Generic 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
21 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Generic 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)
22 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
THANK YOU
23 |
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda