EU CTD

1
EU ??? ???? ??? CTD

• ? 2? QC/QA Workshop
• (2004? 4? 12? )
• ? ? ?
• MJ Pharma

2
Contents

• ? EU ??? ???? ??
• ? Common Technical Document (CTD)

3
Acronyms

• API Active Pharmaceutical Ingredient
• ASM Active Substance Manufacturer
• CEP Certificate of Suitability to the
  Monographs
• of the European Pharmacopoeia,
• called sometimes as COS
• CTD Common Technical Document
• EDMF European Drug Master File
• ICH International Conference on
  Harmonization
• MA Marketing Authorization
• MRP Mutual Recognition Procedures
• NCE New Chemical Entity
• NTA Notice To Applicants

4
EU ??? ???? ?? - focusing on API
5
EU ??? ? ????? ??

• ? EU ??? ? ????? ??? ?? ????? ?? ?????? ??????
  ? ????? ???? ?? ?? ????? ????(MA) ?? ? ??? ???
  ?? ?? ????? ?? ??? ??? ?? ???? ????? ?? ??.
• ?, ??????? ?? ? ????? ??.

6
EU ??? ? ????

• 1. National Authorization (Decentralized
  Procedure)
• - ???? ???? ??
• - EU ? ?? ??? ????
• - ??????(MRP)? ??? ?
• 2. Community Authorization (Centralized
  Procedure)
• - ?????? ? ???? ??? ??? ???? ??
• - EMEA (European Agency for the Evaluation of
  
• Medicinal Product)? ????? CPMP ?? ????
• - Single MA in EU

7

????? ??????(MRP)

• 1. 1998? 1? 1??? ??? ??
• 2. Centralized Procedure? ??? ?? ???? ???
• ?????? ??? ??
• 3. ???? EU? ?? ??? ????? ? ?? ?? ?
• ???? ? ??? ????? ???? EU?????
• ???? ?? ??
• 4. ??? 5?? ??

8

MA ????? ??

• 1. Centralized Procedure? ?? ???, Mutual
• Recognition? ??? National Procedure? ?? ???
• MA Application Dossier? ?? ??? ???.
• 2. MA ???? Format Change
• From 1st July 2003,
• All new applications should be made in accordance
• with the EU-CTD Format
• NTA Format ? CTD Format

9


MA ????? ??

• NTA Format
• Table of Contents 4 Parts
• Part 1. Summary of the Dossier
• Part 2. Chemical, Pharmaceutical and Biological
  
• Documentation
• Part 3. Pharmaco-Toxicological Documentation
• Part 4. Clinical Documentation

10


MA ????? ??

• CTD Format
• Table of Contents 5 Modules
• Module 1. Administrative Information and
  Prescribing
• Information
• Module 2. Common Technical Document Summaries
• Module 3. Quality
• Module 4. Non-clinical Study Reports
• Module 5. Clinical Study Reports

11

????? ???? ??? 3?? ??

• 1. CEP
• Module 3.2.S? ???? ??? CEP Copy ? ??,
• (CEP ??? ?? ??? Application ??)
• EP????? ??? ?????? ?? ???? ???.
• 2. EDMF
• Module 3.2.S? ???? ??? EDMF ??? ??,
• ????? ???? ????? ?????? ?? ??
• ??.
• 3. Full Details of Manufacture
• Module 3.2.S? ???? ??? MA??? ????,
• ????? ???? ????? ?????? ?? ??.

12

CEP

• 1. 1993?? ??? ??
• 2. ?????? ?????? ??? ? ??? ?? ???
• ?? ?????? ? ?? ? ??? ??? ?? ???
• Control ? ? ???? ???? ??
• 3. ????
• EDQM (European Directorate for the Quality of
  
• Medicines) Strasbourg, France

13

CEP
14

EDMF

• 1. Applicant Part (Open Part)
• ????? ???(ASM)? ?? ????? ?????
• (Applicant)?? ???? ???? MA??? ??? ?.
• Applicant? ??? ?????? ??? ????? ??
• ? ???? ?? ??.
• 2. ASM Restricted Part (Closed Part)
• ASM? ?? ??????? ???? ??.
• ????? ???? know-how? ?? ??.

15

EDMF
16

Scheduling for EU Registration
? CEP Procedure ?? ?
Product Launching (Patent Expiry)
???? ????? ??? ?? ?? ? ??? ???? ??? ? ??.
17

Scheduling for EU Registration
? EDMF Procedure ?? ?
???? ????? ??? ?? ?? ? ??? ???? ??? ? ??.
18
Common Technical Document (CTD) - based on EU CTD

19
What is the CTD?

The CTD is an internationally agreed upon
format for the preparation of a well structured
presentation for applications to be submitted to
regulatory authorities in the three ICH regions
of Europe, USA and Japan.
20
The Purpose of Format Change

? It is intended to save time and resources
and to facilitate regulatory review and
communication. ? Through the
harmonization, to avoid the need to generate and
compile different registration dossiers for all
three regions.
21
Scope

? All types of MA irrespective of the
procedure (Centralized, MR or
National). ? All types of products
(NCE, Radiopharmaceutical, Vaccines,
Hervals etc.).
22

CTD Format
Diagrammatic Representation of the Organization
of the CTD

23

CTD Format (Module 1)
Module 1. Administrative Information and
Prescribing Information Module 1.1
Comprehensive Table of Contents Module 1.2
Application Form Module 1.3 Summary of Product
Characteristics, Labeling
and Package Leaflet, etc Module 1.4 Information
about the Experts Module 1.5 Specific
Requirements for Different
Types of Application Annex
Environmental Risk Assessment
24

CTD Format (Module 2)
Module 2. Common Technical Document
Summaries Module 2.1 Overall CTD
Table of Contents Module 2.2 Introduction
Product profile Module 2.3 Quality Overall
Summary Expert report Module 2.4 Non clinical
Overview Expert report Module 2.5 Clinical
Overview Expert report Module 2.6 Nonclinical
Written and Tabulated
Summary Module 2.7 Clinical Summary
25

CTD Format (Module 3 4)
Module 3. Quality Module 3.1 Table of
Contents Module 3.2 Body of Data Module 3.3
Literature References Module 4 . Nonclinical
Study Reports Module 4.1 Table of
Contents Module 4.2 Study Reports Module 4.3
Literature References
26

CTD Format (Module 5)
Module 5. Clinical Study Reports Module
5.1 Table of Contents Module 5.2 Tabular
Listing of All Clinical Studies Module 5.3
Clinical Study Reports Module 5.4 Literature
References
27

Body of Data (Module 3.2)

• 3.2.S Drug Substance
• 3.2.S.1 General Information
• 3.2.S.2 Manufacture
• 3.2.S.3 Characterization
• 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

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Body of Data (Module 3.2)

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

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Organization of CTD (General)

• Applicants should not modify the overall
  organization of
• the CTD outlined in the relevant guidelines.
• ? Text and Tables
• - A4 Paper(8.5 x11 Paper for US),
• - Sufficient margin in the left-hand,
• - 12-Point font of Times New Roman
• ? Pagination
• Every page should be numbered
• ? Acronyms and Abbreviations
• Define in the first time they are used in
  each module

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Organization of CTD (Content)

• ? Module 1. Administrative Information and
• Prescribing Information
• Contains region specific information, content
  
• and format of this module is specified by the
  
• relevant regulatory authorities.

31

Organization of CTD (Content)
? Module 2. Common Technical Document
Summaries Introduction
should not exceed one page. Summary
information should be presented as
described in the following guidelines -
Quality Overall Summary ICH M4Q -
Non-clinical Summary ICH M4S -
Clinical Summary ICH M4E
32

Organization of CTD (Content)
? Module 3. Quality Information on
Quality should be presented in the
structured format described in Guideline ICH
M4Q. ? Module 4 . Non-clinical Study Reports
The non-clinical study reports should be
presented in the order described in
Guideline ICH M4S. ? Module 5. Clinical Study
Reports The human study reports and related
information should be presented in the
order described in Guideline ICH M4E.
33

Organization of CTD (Format)
? Definition of Document - CTD??? ??? ???
????? ?? ?? Section?? ??4. - ???
Section? ???? ?? ?? ??? ??? ??? ?????
???? ?. - Module 4? ?? ? Study Report? ???
??? ?? ?? ???? ?. - Module 5? ??
?? ? Study Report? ?? ?? ??(Core document
and Appendices)? ??? ? ?. -
Literature Reference? ?? ? Reference? ?? ?
??? ???.
34

Organization of CTD (Format)
? Document Pagination and Segregation - ???
???? Page 1?? ???? ??? ???. (Literature
Reference? ?? ??) - ??? ?? Page?? ? ??? ???
??? ? ? ?? ??? ?? ???? ???
?(Identifier).
35

Organization of CTD (Format)
? Section Numbering within Documents - CTD
Guideline??? 5?? ??(5th level Heading) ???
Section Number? ???? ??. - Applicant?
Section?? Sub-heading number? ??? ? ??.
Use of full numbering system (e.g.,
3.2.S.2.2.1) Use of shortened numbering
system under the defined section
number (e.g., under the section number
3.2.S.2.2 1, 1.1, 1.1.1 etc.)
36

Organization of CTD (Format)
? Table of Contents(TOC) Formatting -
Module 2 2.1 CTD TOC third(e.g.,
2.3.S) or fourth level(e.g.,
2.3.S.1) - Module 3
3.1 CTD TOC fifth level only(e.g., 3.2.P.2.1).
TOC title entries should correspond to
as defined in the M4Q Guidelines.
TOC should not specify any page numbers.

37

Organization of CTD (Format)
? Table of Contents(TOC) Formatting -
Module 4 4.1 CTD TOC include all of the
numerical items listed in the CTD
guideline and should continue down to
at least the level of the study
report. Each study report should be
identified in the TOC.
38

Organization of CTD (Format)
? Table of Contents(TOC) Formatting -
Module 5 5.1 CTD TOC include all of
the numerical items listed in the CTD
guideline and should continue down to
at least the level of the study
report. Each study report should be
identified in the TOC.
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CTD for EDMF
? ASM - Module 3.2.S? ?? Guideline (ICH
M4Q) ? ?? CTD Format?? ??. -
Complete EDMF(Open Part? Closed Part)? ??
Authority? MA ?? ????? ?? ??. - Letter of
Access ??. ? MA Applicant - MA?? Section
3.2.S? Open Part(Applicant Part) ??.
- Module 1.2 Application Form Annex 6.10?
Letter of Access ??.
40

CTD for CEP
? ASM - Module 3.2.S? ?? Guideline (ICH M4Q)
? ?? CTD Format?? ??. -
Complete CEP Dossier EDQM? ??. - CEP ??. ?
MA Applicant - Module 1.2 Application Form?
Annex 6.10? CEP Complete Copy ??.
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References

• (1) Notice to Applicants, Volume 2B
  incorporating the Common Technical Document (CTD)
  (July 2003)
• (2) Certification of suitability of the
  monographs of the European Pharmacopoeia
  Resolution AP-CSP (99)4
• (3) Guideline on Active Substance Master File
  Procedure
• (CPMP/QWP/227/02)
• (4) ICH M4, Organization of Common Technical
  Document (CPMP/ICH/2887/99 Rev 1 Organization
  CTD)
• (5) ICH M4Q, Quality Overall Summary of Module 2
  and Module 3 Quality (CPMP/ICH/2887/99 Rev 1
  Quality)
• (6) ICH M4S, Nonclinical Overview and
  Nonclinical Summaries of Module 2 and
  Organization of Module 4
• (CPMP/ICH/2887/99 Rev 1 Safety)
• (7) ICH M4E, Clinical Overview and Clinical
  Summary of Module 2 and Module 5 Clinical Study
  Reports(CPMP/ICH/2887/99 Rev 1 Efficacy)

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Questions?

• MJ Pharma, ?? ???
• ????? ??? ??? 837-17 ????? 713?
• Tel. [phone]
• Fax [phone]
• E-Mail kscho_at_mjpharma.pe.kr