Table of Contents

ICH E2B Expert Working Group Implementation Guide for Electronic Transmission of Individual Case Safety Reports (ICSRs)
E2B(R3) Data Elements and Message Specification
Version 5.01, 12 April 2013

INTRODUCTION
1.0 Purpose..................................................................................................................................................................................... 13
1.1 Scope..........................................................................................................................................................................................13
1.2 Business Case..............................................................................................................................................................................13
2.0 Background.............................................................................................................................................................................. 14
2.1 General Background and History of ICH...................................................................................................................................14
2.2 Development of ICSR Standard under Joint Initiative................................................................................................................16
2.3 Background of Message Standard................................................................................................................................................16
2.4 Representation of the Electronic ICSR........................................................................................................................................17
3.0 Essential Components.............................................................................................................................................................. 20
3.1 ICH ICSR Relational Diagrams..................................................................................................................................................20
3.2 Code Sets, Terminologies and Vocabularies for E2B(R3).............................................................................................................22
3.3 ICH E2B(R3) Specifications for the Transmission of ICSRs........................................................................................................31
3.4 ICH E2B(R3)DATA ELEMENTS............................................................................................................................................. 40
N.1 ICH ICSR Transmission Identification (batch wrapper).......................................................................................................... 40
N.1.1 Type of Messages in Batch.......................................................................................................................................................40
N.1.2 Batch Number........................................................................................................................................................................41
N.1.3 Batch Sender Identifier...........................................................................................................................................................41
N.1.4 Batch Receiver Identifier.........................................................................................................................................................42
N.1.5 Date of Batch Transmission.....................................................................................................................................................42
N.2.r ICH ICSR Message Header (message wrapper) (repeat as necessary)..................................................................................... 42
N.2.r.1 Message Identifier.................................................................................................................................................................42
N.2.r.2 Message Sender Identifier......................................................................................................................................................43
N.2.r.3 Message Receiver Identifier...................................................................................................................................................43
N.2.r.4 Date of Message Creation.....................................................................................................................................................43
C.1 Identification of the Case Safety Report................................................................................................................................... 44
C.1.1 Sender’s (case) Safety Report Unique Identifier........................................................................................................................45
C.1.2 Date of Creation.....................................................................................................................................................................46
C.1.3 Type of Report........................................................................................................................................................................47
C.1.4 Date Report Was First Received from Source..........................................................................................................................47
C.1.5 Date of Most Recent Information for This Report...................................................................................................................48
C.1.6 Additional Available Documents Held by Sender....................................................................................................................48
C.1.7 Does This Case Fulfil the Local Criteria for an Expedited Report?...........................................................................................49
C.1.8 Worldwide Unique Case Identification....................................................................................................................................50
C.1.9 Other Case Identifiers.............................................................................................................................................................51
C.1.10.r Identification Number of the Report Linked to This Report (repeat as necessary)...............................................................53
C.1.11 Report Nullification/Amendment.........................................................................................................................................53
C.2.r Primary Source(s) of Information (repeat as necessary)......................................................................................................... 55
C.2.r.1 Reporter’s Name....................................................................................................................................................................56
C.2.r.2 Reporter’s Address and Telephone.........................................................................................................................................57
C.2.r.3 Reporter’s Country Code......................................................................................................................................................59
C.2.r.4 Qualification.........................................................................................................................................................................60
C.2.r.5 Primary Source for Regulatory Purposes................................................................................................................................60
C.3 Information on Sender of Case Safety Report.......................................................................................................................... 61
C.3.1 Sender Type.............................................................................................................................................................................61
C.3.2 Sender’s Organisation..............................................................................................................................................................62
C.3.3 Person Responsible for Sending the Report.............................................................................................................................62
C.3.4 Sender’s Address, Fax, Telephone and E-mail Address..............................................................................................................64
C.4.r Literature Reference(s) (repeat as necessary).......................................................................................................................... 67
C.4.r.1 Literature Reference(s)..........................................................................................................................................................67
C.4.r.2 Included Documents.............................................................................................................................................................67
C.5 Study Identification.................................................................................................................................................................. 68
C.5.1.r Study Registration (repeat as necessary).................................................................................................................................68

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 C.5.2 Study Name............................................................................................................................................................................69
C.5.3 Sponsor Study Number...........................................................................................................................................................69
C.5.4 Study Type Where Reaction(s)/Event(s) Were Observed..........................................................................................................70
D Patient Characteristics................................................................................................................................................................ 71
D.1 Patient (name or initials)............................................................................................................................................................75
D.2 Age Information........................................................................................................................................................................77
D.3 Body Weight (kg).......................................................................................................................................................................79
D.4 Height (cm)...............................................................................................................................................................................80
D.5 Sex.............................................................................................................................................................................................80
D.6 Last Menstrual Period Date........................................................................................................................................................80
D.7 Relevant Medical History and Concurrent Conditions (not including reaction/event)...............................................................81
D.8.r Relevant Past Drug History (repeat as necessary).....................................................................................................................84
D.9 In Case of Death........................................................................................................................................................................89
D.10 For a Parent-child/Foetus Report, Information Concerning the Parent................................................................................. 92
D.10.1 Parent Identification.............................................................................................................................................................92
D.10.2 Parent Age Information.........................................................................................................................................................92
D.10.3 Last Menstrual Period Date of Parent....................................................................................................................................93
D.10.4 Body Weight (kg) of Parent...................................................................................................................................................93
D.10.5 Height (cm) of Parent...........................................................................................................................................................94
D.10.6 Sex of Parent.........................................................................................................................................................................94
D.10.7 Relevant Medical History and Concurrent Conditions of Parent..........................................................................................94
D.10.8.r Relevant Past Drug History of Parent (repeat as necessary).................................................................................................96
E.i REACTION(S)/EVENT(S) (REPEAT AS NECESSARY)......................................................................................................... 100
E.i.1 Reaction/Event as Reported by the Primary Source.................................................................................................................101
E.i.2.1 Reaction/Event (MedDRA code).........................................................................................................................................101
E.i.3.1 Term Highlighted by the Reporter.......................................................................................................................................102
E.i.3.2 Seriousness Criteria at Event Level (more than one can be chosen)......................................................................................102
E.i.4 Date of Start of Reaction/Event..............................................................................................................................................104
E.i.5 Date of End of Reaction/Event...............................................................................................................................................105
E.i.6 Duration of Reaction/Event....................................................................................................................................................105
E.i.7 Outcome of Reaction/Event at the Time of Last Observation.................................................................................................106
E.i.8 Medical Confirmation by Healthcare Professional..................................................................................................................106
E.i.9 Identification of the Country Where the Reaction/Event Occurred........................................................................................107
F.r Results of Tests and Procedures Relevant to the Investigation of the Patient (repeat as necessary)........................................... 107
F.r.1 Test Date.................................................................................................................................................................................108
F.r.2 Test Name...............................................................................................................................................................................108
F.r.3 Test Result...............................................................................................................................................................................109
F.r.4 Normal Low Value..................................................................................................................................................................111
F.r.5 Normal High Value.................................................................................................................................................................111
F.r.6 Comments (free text)..............................................................................................................................................................111
F.r.7 More Information Available.....................................................................................................................................................112
G.k DRUG(S) INFORMATION (REPEAT AS NECESSARY)...................................................................................................... 113
G.k.1 Characterisation of Drug Role...............................................................................................................................................115
G.k.2 Drug Identification...............................................................................................................................................................116
G.k.3 Holder and Authorisation / Application Number of Drug.....................................................................................................121
G.k.4.r Dosage and Relevant Information (repeat as necessary).......................................................................................................122
G.k.5 Cumulative Dose to First Reaction........................................................................................................................................129
G.k.6 Gestation Period at Time of Exposure...................................................................................................................................129
G.k.7.r Indication for Use in Case (repeat as necessary)..................................................................................................................130
G.k.8 Action(s) Taken with Drug....................................................................................................................................................131
G.k.9.i Drug-reaction(s)/Event(s) Matrix (repeat as necessary)........................................................................................................131
G.k.10.r Additional Information on Drug (coded) (repeat as necessary)..........................................................................................135
G.k.11 Additional Information on Drug (free text).........................................................................................................................136
H NARRATIVE CASE SUMMARY AND FURTHER INFORMATION...................................................................................... 137
H.1 Case Narrative Including Clinical Course, Therapeutic Measures, Outcome and Additional Relevant Information..................137
H.2 Reporter’s Comments..............................................................................................................................................................138
H.3.r Sender’s Diagnosis (MedDRA code) (repeat as necessary)......................................................................................................138
H.4 Sender’s Comments.................................................................................................................................................................139
H.5.r Case Summary and Reporter’s Comments in Native Language (repeat as necessary)..............................................................139
3.5 DOCUMENT ATTACHMENTS............................................................................................................................................ 140

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 3.5.1 User Guidance.......................................................................................................................................................................140
3.5.2 Technical specification............................................................................................................................................................140
3.5.3 Examples of XML instances...................................................................................................................................................141
4.0 THE ICSR ACKNOWLEDGEMENT TRANSACTION......................................................................................................... 142
4.1 Acknowledgement Message in HL7..........................................................................................................................................142
4.2 ICH ICSR Acknowledgement Message.....................................................................................................................................142
ACK.M / A ICH ICSR Batch Acknowledgement.......................................................................................................................... 144
ACK.M.1 Acknowledgement Batch Number..................................................................................................................................144
ACK.M.2 Acknowledgement Batch Sender Identifier.....................................................................................................................144
ACK.M.3 Acknowledgement Batch Receiver Identifier...................................................................................................................145
ACK.M.4 Acknowledgement Date of Batch Transmission..............................................................................................................145
ACK.A.1 ICSR Batch Number.......................................................................................................................................................146
ACK.A.2 Acknowledgement Local Message Number......................................................................................................................146
ACK.A.3 Date of ICSR Batch Transmission....................................................................................................................................146
ACK.A.4 Transmission Acknowledgement Code.............................................................................................................................147
ACK.A.5 Batch Validation Error.....................................................................................................................................................147
ACK.B ICH ICSR Message Acknowledgement............................................................................................................................. 147
ACK B.r.1 ICSR Message Number.................................................................................................................................................147
ACK.B.r.2 Local Report Number....................................................................................................................................................147
ACK.B.r.3 ICSR Message ACK Receiver.........................................................................................................................................148
ACK.B.r.4 ICSR Message ACK Sender...........................................................................................................................................148
ACK.B.r.5 Date of ICSR Message Creation....................................................................................................................................148
ACK.B.r.6 Acknowledgement Code for a ICSR MessageACK.B.r.7 Error/Warning Message or Comment.....................................149
APPENDICES.............................................................................................................................................................................. 150
APPENDIX I—PREPARING AND SENDING ICH ICSRS:....................................................................................................... 150
Appendix I (A)—ICH ICSR SCHEMAs........................................................................................................................................150
Appendix I (B) – Backwards & Forwards Compatibility.................................................................................................................155
Appendix I (C) – Schema files.........................................................................................................................................................155
Appendix I (D) – Reference Instances for ICH ICSR message and ICSR Acknowledgement message.............................................155
Appendix I (E) – Example Instances of report cases.........................................................................................................................155
Appendix I (F) – ICH E2B code lists..............................................................................................................................................156
Appendix I (G) – Technical Information.........................................................................................................................................156
Appendix I (H) – SGML & XML conversion\................................................................................................................................156
APPENDIX II – DATE/TIME...................................................................................................................................................... 157
Appendix II (A) Date/Time............................................................................................................................................................157
Appendix II (B) Time Zone............................................................................................................................................................158
Appendix II (C) ISO 8601 Compliant XML Examples...................................................................................................................158
APPENDIX III - ABBREVIATIONS and GLOSSARY OF TERMS.............................................................................................. 159
Appendix III (A)ABBREVIATIONS..............................................................................................................................................159
Appendix III (B) GLOSSARY of TERMS.......................................................................................................................................161

ICH M2 EWG Electronic Common Technical Document Specification....................................................................................... 165

ICH eCTD Specification.............................................................................................................................................................. 167
Introduction...................................................................................................................................................................................167
Background.....................................................................................................................................................................................167
Scope..............................................................................................................................................................................................167
Technical Requirements..................................................................................................................................................................167
Change Control..............................................................................................................................................................................167
Appendix 1: Overall Architecture.................................................................................................................................................. 169
Guiding Design Principles..............................................................................................................................................................169
Business Model...............................................................................................................................................................................169
Modular Structure of the eCTD.....................................................................................................................................................169
XML Based eCTD..........................................................................................................................................................................169
Multiple Region Support................................................................................................................................................................170
Life Cycle Management..................................................................................................................................................................170
Appendix 2: The eCTD Submission.............................................................................................................................................. 171
Introduction...................................................................................................................................................................................171
The eCTD Submission....................................................................................................................................................................171
eCTD Template..............................................................................................................................................................................171

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 Formats...........................................................................................................................................................................................171
Common Formats...........................................................................................................................................................................172
Regional Use of Other Formats.......................................................................................................................................................172
Links...............................................................................................................................................................................................172
Presentation....................................................................................................................................................................................172
Checksums......................................................................................................................................................................................172
Element to File Directory Mapping.................................................................................................................................................172
File Extension.................................................................................................................................................................................173
Name..............................................................................................................................................................................................173
Character encoding.........................................................................................................................................................................174
References.......................................................................................................................................................................................174
Appendix 3: General Considerations for the CTD Modules......................................................................................................... 176
Introduction...................................................................................................................................................................................176
Folder and File Naming Conventions..............................................................................................................................................176
Screenshots and Folder Hierarchy...................................................................................................................................................177
Module 1 Administrative Information and Prescribing Information................................................................................................177
Module 2 Summaries......................................................................................................................................................................177
Module 3 Quality...........................................................................................................................................................................179
Module 4 Nonclinical Study Reports..............................................................................................................................................182
Module 5 Clinical Study Reports....................................................................................................................................................185
Appendix 4: File Organization for the eCTD................................................................................................................................ 192
Appendix 5: Region Specific Information Including Transmission and Receipt............................................................................ 257
Introduction...................................................................................................................................................................................257
Region Specific Information: Module 1..........................................................................................................................................257
Submission Addresses......................................................................................................................................................................257
Media.............................................................................................................................................................................................258
Cover Letter....................................................................................................................................................................................258
Transport........................................................................................................................................................................................258
Security...........................................................................................................................................................................................258
Receipt............................................................................................................................................................................................259
Acknowledgment............................................................................................................................................................................259
Appendix 6: The eCTD XML Submission..................................................................................................................................... 260
Background.....................................................................................................................................................................................260
File Names and Directory Structure................................................................................................................................................260
Lifecycle Management....................................................................................................................................................................261
Operation Attribute........................................................................................................................................................................262
File Reuse........................................................................................................................................................................................264
DTD Content Model.....................................................................................................................................................................265
eCTD Element/Attribute Instructions............................................................................................................................................267
Example 6-1: Instructions for a Simple New Submission................................................................................................................270
Example 6-2: Instructions for an Amendment, Supplement, or Variation.......................................................................................271
Example 6-3: Instructions for Multiple Indications.........................................................................................................................271
Example 6-4: Instructions for Multiple Drug Substances, Manufacturers, and Products..................................................................272
Example 6-5: Instructions for Extending XML eCTD DTD Elements...........................................................................................274
Example 6-6: Instructions for Submitting Sections as Paper............................................................................................................274
Appendix 7: Specification for Submission Formats....................................................................................................................... 276
Introduction...................................................................................................................................................................................276
PDF................................................................................................................................................................................................276
XML Files.......................................................................................................................................................................................280
SVG Files........................................................................................................................................................................................280
Appendix 8: XML eCTD DTD..................................................................................................................................................... 282

ICH M8 Expert Working Group 16 17 18 19 20 21 22 ICH Electronic Common Technical Document (eCTD) v4.0 23
DRAFT ICH Implementation Guide v1.0 24 .....................................................................................................................................296
Notice to Readers.......................................................................................................................................................................... 298
Instructions to Reader.................................................................................................................................................................. 299
Document Content.........................................................................................................................................................................299
Common Terms ‐ TBD...................................................................................................................................................................300
XML Snippets.................................................................................................................................................................................301

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 XML Elements Tables.....................................................................................................................................................................302
1. Purpose..................................................................................................................................................................................... 303
1.1 Scope........................................................................................................................................................................................303
1.2 Business Case............................................................................................................................................................................303
2. Background.............................................................................................................................................................................. 304
2.1 General Background and History..............................................................................................................................................304
2.2 The Framework for the ICH eCTD v4.0..................................................................................................................................305
2.3 Advantages of eCTD v4.0.........................................................................................................................................................305
2.4 Change Control........................................................................................................................................................................306
3. Essential Components of the eCTD v4.0.................................................................................................................................. 307
3.1 Files and Folder.........................................................................................................................................................................308
3.2 Controlled Vocabularies............................................................................................................................................................308
3.3 ICH eCTD v4.0 XML Schema.................................................................................................................................................309
3.4 The eCTD 4.0 XML Message...................................................................................................................................................311
3.5 OIDS and UUIDS....................................................................................................................................................................311
3.6 Data Types................................................................................................................................................................................312
3.7 Regional/Module 1 Implementation Guides.............................................................................................................................312
4. Submission Contents, Folder and File Structure....................................................................................................................... 314
4.1 Submission Unit Contents........................................................................................................................................................315
4.2 Naming Conventions................................................................................................................................................................315
4.3 Pathname Conventions and Best Practices.................................................................................................................................317
4.4 Folder Hierarchy.......................................................................................................................................................................317
4.5 File Formats..............................................................................................................................................................................318
4.6 Checksums................................................................................................................................................................................318
4.7 Compressed Archive..................................................................................................................................................................318
5. Controlled Vocabularies............................................................................................................................................................ 318
5.1 Controlled Vocabularies specified by ICH.................................................................................................................................318
5.2 Controlled Vocabularies specified Regionally.............................................................................................................................319
5.3 Controlled Vocabulary specified by HL7...................................................................................................................................321
5.4 Controlled Vocabulary specified by Others................................................................................................................................321
6. ICH eCTD v4.0 XML Schema.................................................................................................................................................. 322
6.1 Core Schema.............................................................................................................................................................................322
6.2 eCTD v 4.0 Schema.................................................................................................................................................................322
7. eCTD 4.0 XML Message........................................................................................................................................................... 324
7.1 Message Header........................................................................................................................................................................324
7.2 Payload Message........................................................................................................................................................................325
8. Implementation Scenarios........................................................................................................................................................ 383
8.1 Dossier Management................................................................................................................................................................384
8.2 Documents...............................................................................................................................................................................384
8.3 Context of Uses/Context of Use Keywords................................................................................................................................386
8.4 Managing Context of Uses........................................................................................................................................................387
8.5 Other Considerations................................................................................................................................................................392
8.6 Approaches to Changes in Document Granularity....................................................................................................................395
9. Validation of the eCTD v4.0 Message....................................................................................................................................... 401
10. Compatibility and Reference to eCTD V3.2.2........................................................................................................................ 402
11. Appendix 1 Sample Files and Folders for Modules 2‐5........................................................................................................... 403
11.1 Module 2 Summaries..............................................................................................................................................................403
11.2 Module 3 Quality...................................................................................................................................................................403
11.3 Module 4 Nonclinical Study Reports......................................................................................................................................407
11.4 Module 5 Clinical Study Reports............................................................................................................................................410
12. Appendix 2 Sample eCTD Messages....................................................................................................................................... 417
13. Appendix 3 Abbreviations, Terms and Definitions.................................................................................................................. 417
14. Appendix 4 References............................................................................................................................................................ 417
15. Appendix 5 eCTD v4.0 Schema.............................................................................................................................................. 417

LIST OF FIGURES
Figure 1: Allowable Special Characters...................................................................................................................................................316
Figure 2: Sample Folder Hierarchy of Module 2.....................................................................................................................................317
Figure 3: Module 2 Folder Structure......................................................................................................................................................403
Figure 4: Module 3 Folder Structure......................................................................................................................................................406

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Figure 5: Module 4 Folder Structure......................................................................................................................................................409
Figure 6: Module 5 Folder Structure......................................................................................................................................................414

LIST OF TABLES
Table 1: Legend of Symbols used in Document......................................................................................................................................299
Table 2: Legend for XML Snippets.........................................................................................................................................................301
Table 3: Sample XML Element Table.....................................................................................................................................................302
Table 4: XML Structure.........................................................................................................................................................................326

Guidance for Industry Providing Regulatory Submissions in Electronic Format—Certain Human Pharmaceutical Product
Applications and Related Submissions Using the eCTD Specifications (DRAFT GUIDANCE).................................................... 408
I. INTRODUCTION.................................................................................................................................................................... 421
II. REQUIREMENT TO SUBMIT ELECTRONICALLY............................................................................................................. 423
A. For what submission types is an electronic submission required?..............................................................................................423
B. Are there other submission types not subject to the electronic submission requirement for which electronic submission is
recommended?.........................................................................................................................................................................423
C. What types of submissions are exempted from the electronic submission requirement?............................................................423
D. Will FDA issue waivers of Electronic Submission Requirements?.............................................................................................424
E. What are the requirements that I must follow?.........................................................................................................................424
III.GENERAL CONSIDERATIONS............................................................................................................................................ 426
A. Document Granularity and Table of Contents Headings.........................................................................................................426
B. Resubmission of Previous Submissions....................................................................................................................................427
C. Referencing Previously Submitted Documents........................................................................................................................427
D. File Formats and Versions........................................................................................................................................................427
E. Leaf Titles................................................................................................................................................................................428
F. Transmission of Electronic Submissions...................................................................................................................................428
G. Receipt Date of Electronic Submissions...................................................................................................................................428
H. Submission of Paper Copies.....................................................................................................................................................428
I. The FDA District Office Copy................................................................................................................................................429
IV. ORGANIZATION OF THE eCTD................................................................................................................................ 430
A. Module 1 Administrative Information and Prescribing Information Folder.............................................................................430
B. Module 2 Summary Folder......................................................................................................................................................432
C. Module 3 Quality Folder.........................................................................................................................................................433
D. Module 4 Nonclinical Folder...................................................................................................................................................434
E. Module 5 Clinical Folder.........................................................................................................................................................435
CONTACT INFORMATION....................................................................................................................................................... 438
REFERENCE LIST....................................................................................................................................................................... 439

CMDh BEST PRACTICE GUIDE ON THE USE OF THE ELECTRONIC COMMON TECHNICAL DOCUMENT (eCTD) IN THE
MUTUAL RECOGNITION AND DECENTRALISED PROCEDURES Doc. Ref.:CMDh/084/2008/Rev3 November 2011 .................578
1. INTRODUCTION.......................................................................................................................................................................579
2. GENERAL CONCEPTS...............................................................................................................................................................579
2.1. Comprehensive Model...........................................................................................................................................................579
2.2 Tracking Table.......................................................................................................................................................................580
2.3. Transition from Parallel National Model to Comprehensive Model........................................................................................580
3. DECENTRALISED PROCEDURE (DCP)..................................................................................................................................581
3.1 Validation and Assessment.....................................................................................................................................................581
3.2 Submission of National Translations of Product Information.................................................................................................582
3.3 Subsequent Lifecycle Submissions..........................................................................................................................................582
4. MUTUAL RECOGNITION PROCEDURE (MRP)....................................................................................................................582
4.1 National Phase.......................................................................................................................................................................582
4.2 Start of MRP.........................................................................................................................................................................583
4.3 Validation and assessment......................................................................................................................................................584
4.4 Submission of National Translations of Product Information.................................................................................................586
4.5 Variations and Other Procedures that Affect the RMS and all CMSs (Generally-Applicable Lifecycle Submissions)...............586
4.6 Procedures that Affect Only a Single CMS (Country-Specific Lifecycle Submissions)............................................................587
4.7 Repeat Use Procedures...........................................................................................................................................................588
4.8 Change of RMS.....................................................................................................................................................................589

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 4.9 Switch from paper or NeeS to eCTD.....................................................................................................................................590
4.10 Use of the eCTD format for “Mixed Format Applications”....................................................................................................590
5. SUMMARY.......................................................................................................................................................................................590
TABLES.................................................................................................................................................................................................591

Practical Guidance For the Paper Submission of Regulatory Information in Support of a Marketing Authorisation Application
When Using an eCTD or NeeS as the Source Submission (v2.0 March 2010)....................................................................................599
1 Background.....................................................................................................................................................................................602
2 Rationale.........................................................................................................................................................................................602
3 Purpose of this document................................................................................................................................................................602
4 Scope..............................................................................................................................................................................................602
5 Printing by Agency or Applicant.....................................................................................................................................................602
6 Number of Printed Paper Copies Required.....................................................................................................................................603
7 Structure of the Printed eCTD or NeeS..........................................................................................................................................603
8 Provision of Tabs for the Printed eCTD or NeeS.............................................................................................................................603
9 Printed Table of Contents (ToC).....................................................................................................................................................603
9.1 eCTD.......................................................................................................................................................................................603
9.2 NeeS.........................................................................................................................................................................................604
10 Headers and Footers........................................................................................................................................................................604
11 Printed Application Form...............................................................................................................................................................604
12 Reference to Previous Submissions & Lifecycle Attributes...............................................................................................................604
13 Labelling of Individual Volumes—Covers and Spines......................................................................................................................604
Appendix 1—Example Tables of Contents.............................................................................................................................................605
Example ToC for paper accompanying an eCTD, based on index.xml viewed through Internet Explorer and converted to PDF.......605
Example ToC for paper accompanying a NeeS, based on printing the mx-toc.pdf files ......................................................................606

Guidance for Industry—Submitting Marketing Applications According to the ICH-CTD Format—General Considerations
(DRAFT GUIDANCE).................................................................................................................................................................. 615

I. INTRODUCTION.................................................................................................................................................................... 617
II. BACKGROUND...................................................................................................................................................................... 618
III. CTD FORMAT FOR EACH SUBMISSION.......................................................................................................................... 619
A. Module 1—Administrative and Prescribing Information.........................................................................................................619
B. Module 2—Common Technical Document Summaries...........................................................................................................621
C. Module 3—Quality.................................................................................................................................................................622
D. Module 4—Nonclinical Study Reports....................................................................................................................................622
E. Module 5—Clinical Study Reports..........................................................................................................................................623
IV. GENERAL ISSUES FOR SUBMISSIONS.............................................................................................................................. 624
A. Amendments and Supplements................................................................................................................................................624
B. Organizing Documents............................................................................................................................................................624
C. Number of copies....................................................................................................................................................................624
D. Paper size.................................................................................................................................................................................625
E. Paper margins..........................................................................................................................................................................626
F. Fonts........................................................................................................................................................................................626
G. Binding volumes......................................................................................................................................................................626
H. Volume size..............................................................................................................................................................................627
I. Volume numbering..................................................................................................................................................................627
J. Volume identification..............................................................................................................................................................627
K. Pagination................................................................................................................................................................................628
L. Cross referencing documents...................................................................................................................................................628
M. Packing carton.........................................................................................................................................................................628
N. Sending the Submission...........................................................................................................................................................628
V. ELECTRONIC SUBMISSION................................................................................................................................................. 629
VI. QUESTIONS ABOUT PREPARING AND SENDING SUBMISSIONS................................................................................ 629
A. CBER......................................................................................................................................................................................629
B. CDER.....................................................................................................................................................................................629
APPENDIX A: GUIDANCE ON CONTENT OF THE CTD....................................................................................................... 630
APPENDIX B: REGULATORY REQUIREMENTS AND THE CTD.......................................................................................... 631