Guidance for Industry
 
Submitting Marketing Applications 

According to the ICH-CTD Format  

General Considerations 

DRAFT GUIDANCE 
This guidance document is being distributed for comment purposes only. 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication of the Federal Register notice announcing the availability of the draft guidance. 
Submit comments to Dockets Management Branch (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1601, Rockville, MD 20857.  All comments should be identified with the 
docket number listed in the notice of availability that published in the Federal Register. 
For questions on the draft document contact Randy Levin (CDER) 301-594-5400 or Robert 
Yetter (CBER) 301-827-0373. 
U.S. Department of Health and Human Services
 
Food and Drug Administration
 
Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

August 2001 
Procedural 
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08/20/01  Guidance for Industry
 
Submitting Marketing Applications 

According to the ICH-CTD Format  

General Considerations 

Additional copies are available from: 

Office of Training and Communications 

Division of Drug Information HFD-240 

Center for Drug Evaluation and Research 

Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857 

(Tel) 301-827-4573 

http://www.fda.gov/cder/guidance/index.htm 

or

 Office of Communication, Training and 

Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research

 Food and Drug Administration 

1401 Rockville Pike, Rockville, MD 20852-1448

 http://www.fda.gov/cber/guidelines.htm 

Fax: 1-888-CBERFAX or 301-827-3844 

Phone: the Voice Information System at 800-835-4709 or 301-827-1800 

U.S. Department of Health and Human Services
 
Food and Drug Administration
 
Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

August 2001 
Procedural 
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TABLE OF CONTENTS
 
I.  INTRODUCTION................................................................................................................. 1
 
II.  BACKGROUND ................................................................................................................... 2
 
III.  CTD FORMAT FOR EACH SUBMISSION ..................................................................... 3
 
A.  Module 1 - Administrative and Prescribing Information ......................................................3
 
1. FDA form 356h.......................................................................................................................4
 
2. Comprehensive table of contents..............................................................................................4
 
3. Administrative documents........................................................................................................4
 
B.  Module 2  Common Technical Document Summaries.........................................................5
 
1. Overall CTD table of contents .................................................................................................5
 
2. Introduction to the summary documents ...................................................................................5
 
3. Overviews and summaries.......................................................................................................6
 
C.  Module 3 - Quality................................................................................................................6
 
1. Module 3 table of contents.......................................................................................................6
 
2. Body of data...........................................................................................................................6
 
3. Literature References..............................................................................................................6
 
D.  Module 4 - Nonclinical Study Reports...................................................................................6
 
1. Module 4 table of contents.......................................................................................................7
 
2. Study reports and related information......................................................................................7
 
3. Literature References..............................................................................................................7
 
E.  Module 5 - Clinical Study Reports ........................................................................................7
 
1. Module 5 table of contents.......................................................................................................7
 
2. Study reports and related information......................................................................................7
 
3. Literature References..............................................................................................................8
 
IV.  GENERAL ISSUES FOR SUBMISSIONS ........................................................................ 8
 
A.  Amendments and Supplements .............................................................................................8
 
B.  Organizing Documents..........................................................................................................8
 
C.  Number of copies..................................................................................................................8
 
1. Archival copy .........................................................................................................................9
 
2. Review copy ...........................................................................................................................9
 
3. Field copy..............................................................................................................................9
 
D.  Paper size..............................................................................................................................9
 
E.  Paper margins.....................................................................................................................10
 
F.  Fonts...................................................................................................................................10
 
G.  Binding volumes..................................................................................................................10
 
H.  Volume size.........................................................................................................................11
 
I.  Volume numbering .............................................................................................................11
 
J.  Volume identification..........................................................................................................11
 
K.  Pagination...........................................................................................................................12
 
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L.  Cross referencing documents..............................................................................................12
 
M.  Packing carton....................................................................................................................12
 
N.  Sending the Submission......................................................................................................12
 
1. CBER...................................................................................................................................12
 
2. CDER..................................................................................................................................12
 
V.  ELECTRONIC SUBMISSION.......................................................................................... 13
 
VI.  QUESTIONS ABOUT PREPARING AND SENDING SUBMISSIONS ...................... 13
 
A.  CBER..................................................................................................................................13
 
B.  CDER .................................................................................................................................13
 
APPENDIX A:  GUIDANCE ON CONTENT OF THE CTD.................................................. 1
 
APPENDIX B:  REGULATORY REQUIREMENTS AND THE CTD.................................. 1
 
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Guidance for Industry1
 
Submitting Marketing Applications According to the ICH-CTD 

Format  General Considerations 

This draft guidance, when finalized, will represent the Food and Drug Administration's  (FDA's) 
current thinking on this topic.  It does not create or confer any rights for or on any person and does 
not operate to bind FDA or the public.  An alternative approach may be used if such approach 
satisfies the requirements of the applicable statutes and regulations. 
I.  INTRODUCTION 
This is one in a series of guidance documents that provide recommendations for applicants 
preparing a Common Technical Document for the Registration of Pharmaceuticals for Human 
Use (CTD) for submission to the U.S. Food and Drug Administration (FDA).  This guidance 
document is intended to describe how to organize new drug applications (NDAs), abbreviated 
new drug applications (ANDAs), and biological license applications (BLAs) based on the 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) guidelines on the CTD.  This guidance document is 
intended to be used together with the CTD guidances, described below, and when finalized, it 
will supercede Guidelines on Formatting, Assembling, and Submitting of New Drug and 
Antibiotic Applications (February 1987) and the  guidance for industry, Organization of an ANDA 
(February 1998). 
Through the ICH process, considerable harmonization has been achieved among the three 
regions (Japan, Europe, and the United States) in the organization of a submission for the 
registration of pharmaceuticals for human use.   The CTD format and organization are presented 
in a series of four documents, known as the CTD guidances.  The four guidances, which will be 
issued in summer 2001, are titled: 
   M4: Organization of the CTD 
   M4E:  The CTD  Efficacy 
   M4Q:  The CTD  Quality 
   M4S:  The CTD  Safety 
These CTD guidance documents apply to applications for drug and biological pharmaceuticals 
(including biotechnology-derived products) and all related presubmissions, supplements, and 
amendments.  The CTD guidance documents are not intended to indicate what data or studies are 
                                                
1 This guidance was developed by the Center for Drug Evaluation and Research (CDER) in cooperation with the 
Center for Biologics Evaluation and Research (CBER), Food and Drug Administration. 
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required; they merely indicate an appropriate format for the data that have been acquired.  The 
CTD guidance documents are intended to be used together with other ICH and Agency guidance 
documents that provide detailed information about the contents of an application.  Applicants 
should not modify the overall organization of the CTD.   
This guidance document presents general considerations for the overall organization and format 
of the marketing application based on the table of contents described in the CTD guidances.  The 
marketing application is organized into five modules. This guidance describes the format (e.g., 
table of contents) of the region-specific administrative  and prescribing information required by 
the United States in Module 1.  The CTD guidances describe the format and organization of the 
Summaries, Quality, Nonclinical, and Clinical modules (Modules 2 to 5). 
This guidance addresses the organization of an application provided entirely in paper, but we 
also accept NDAs and BLAs in electronic format.  In the United States, regulations are in place 
that allow you to provide marketing applications in electronic format without a paper copy.  In 
addition, for electronic submissions, applicants can provide documents as structured data, rather 
than traditional documents.  We have considered these issues generally in this guidance 
document.  The ICH M2 expert working group is developing ICH guidelines for providing the 
CTD in electronic format. 
II.  BACKGROUND 
To market a drug or biological product in the United States, you must provide adequate 
information to the FDA demonstrating that the product is safe and effective for the conditions 
prescribed, recommended, or suggested in the proposed labeling for the product.  The regulations 
under 21 CFR 314.50, 314.94, and 601.2 describe the information required for the NDA and 
ANDA for drug products and the BLA for biological products, respectively. 
Substantial documentation and data are required in NDA, ANDA, and BLA submissions, 
resulting in large, complex applications.  It is not a simple matter to compile the information or 
to review it.  Applicants have used many different approaches to organizing the information, but 
differences in the organization of each application make reviewing more difficult and may lead 
to omission of critical data or analyses.  Such omissions can result in a decision to refuse to file 
(RTF) an application.  Previous guidance has been provided on how to organize various parts of 
a submission, but because of differing regional requirements, applicants who wanted to make 
submissions to more than one region had to prepare multiple, region-specific submissions. 
Through the ICH process, the CTD guidances have been  developed.   These  guidances  describe 
a  common format  for  the  organization  of applications  that can be used to support registration of 
pharmaceuticals for human use in Japan, the European Union, and the United States. 
Although the content of the application is not significantly changed by the CTD guidances, the 
organization of the information described in the CTD guidances represents a change from the 
way applications are currently arranged in the three regions.  We believe having a standard 
document with common elements will facilitate the development of applications and the 
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regulatory review process and will improve communication among applicants and the three 
regions. 
We are now able to accept and review applications organized as described in the CTD guidances. 
You can submit a BLA for a specified biotechnological product, and an NDA or an ANDA for 
all drug products, in the CTD format.  You can submit BLAs in CTD format for other categories 
of biological products as guidance documents become available for those product categories.  If 
you wish to submit BLAs in the CTD format for those products prior to the availability of 
guidance, you should contact the CBER office with review responsibility prior to developing the 
submission.  The Agency highly recommends that, by 2003, sponsors regularly submit BLAs for 
specified biotechnological products, NDAs, and ANDAs to the Agency in the CTD format. 
An application organized as described in this guidance will fulfill the regulatory format 
requirements for 21 CFR 314.50, 314.94, and 601.2. 
III.  CTD FORMAT FOR EACH SUBMISSION 
According to the CTD format, each submission of a marketing application is a collection of 
documents, grouped into 5 modules as listed in table 1.  This guidance provides information on 
the contents of Module 1:  Administrative and Prescribing Information, which is region specific. 
This guidance also discusses the general organization of Modules 2 to 5, which make up the 
CTD part of the application. The content of the documents contained in the CTD modules is 
outside the scope of this guidance.  Appendix A lists some ICH and FDA documents that discuss 
content and other organizational issues related to each module. 
No changes in regulations are needed to implement the CTD guidance for submission of an 
NDA, ANDA, or BLA.  Appendix B lists the location of regulatory requirements for NDAs, 
ANDAs, and BLAs  in relationship to the modules. 
Table 1: Documents in each Module 
Module  Information 
1  Administrative and prescribing information (region specific) 
2  Summaries and overview 
3  Information on product quality 
4  Nonclinical study reports 
5  Clinical study reports 
A.  Module 1 - Administrative and Prescribing Information 
Module 1 should contain all administrative documents (e.g., application forms, claims of 
categorical exclusion and certifications), and labeling, including the documents described 
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below, as needed.2 Documents should be organized in the order listed below. Generally, 
all of the documents in Module 1 can be provided in a single volume. Environmental 
assessments should be submitted separately. 
1.  FDA form 356h 
The first document in Module 1 should be FDA form 356h. 
2.  Comprehensive table of contents 
The next document in Module 1 should be the comprehensive table of contents for the 
entire submission.  Each NDA and ANDA submission is required to have a 
comprehensive table of contents or index for the entire submission as described in 21 
CFR 314.50 and 314.94.  The comprehensive table of contents significantly enhances the 
usefulness of the document.  It should include a complete list of all documents provided 
in the submission by module. 
In the table of contents, you should identify the location of each document by referring to 
the volume numbers that contain the relevant documents and any tab identifiers.  In 
general, the name for the tab identifier should be the name of the document (e.g., patent 
certification, financial disclosure) or section heading according to the CTD format (e.g., 
3.2.P.4.2).  If the full name of the document is too long for the tab identifiers, you should 
substitute an alternative name that adequately identifies the document.  You should not 
use page numbers in the table of contents to refer to documents, but use tab identifiers as 
described above. 
3.  Administrative documents 
a.  Administrative documents 
You should provide the appropriate administrative documents with the 
submission. Examples of administrative documents are listed below. See 21 CFR 
314.50, 314.94, and 601.2 for details on the administrative documents needed for 
specific submissions.  FDA form 356h lists most of the administrative documents 
to be included in Module 1. The order of such documents should be consistent 
with that in FDA Form 356h. 
   Patent information on any patent that claims the drug, if applicable 
   Patent certifications (not for BLA) 
   Debarment certification 
   Field copy certification (not for BLA) 
   User fee cover sheet 
   Financial disclosure information 
                                                
2 Applicants often choose to submit a cover letter with their submissions. If you plan to include a cover letter, it 
should be placed at the beginning of Module 1. 
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   Letters of authorization for reference to other applications or drug master files 
   Waiver requests 
   Environmental assessment or request for categorical exclusion 
   Statements of claimed exclusivity and associated certifications 
Since these documents are small, you should place them in the same volume, 
separated by tab identifiers.  If you submit an environmental assessment, you 
should provide it as a separate volume. 
b.  Prescribing information 
You should include all copies of the labels and all labeling for the product in 
Module 1.  The type of labeling provided depends on the submission.  Examples 
of prescribing information include container and package labels as well as 
package inserts, draft labeling, patient leaflets, information sheets, and required 
Medication Guides.  You should separate each sample of labeling by tab 
identifiers. 
c.  Annotated labeling text 
For the NDA, you should provide a copy of the proposed labeling text with 
annotations directing reviewers to the information in the summaries and other 
modules that support each statement in the labeling, as described in 21 CFR 
314.50(c)(2)(i).  The annotated labeling text should include the content of the 
labeling described under 21 CFR 201.57 and all text, tables, and figures used in 
the package insert. 
d.  Labeling comparison 
For the ANDA, you should provide the comparison of labeling that is described in 
21 CFR 314.94(a)(8). 
B.  Module 2  Common Technical Document Summaries 
Module 2 should include the summary documents.  You should provide the documents 
for this module in the order described below. 
1.  Overall CTD table of contents 
For the first document in this module, you should provide a comprehensive table of 
contents listing all of the documents provided in the submission for modules 2 through 5. 
2.  Introduction to the summary documents 
You should provide the introduction to the summary described in the guidance document 
M4: Organization of the CTD as a one page document. 
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3.  Overviews and summaries 
Module 2 should contain the following additional documents as described in the 
appropriate guidance documents (M4Q: The CTD -Quality, M4S: The CTD - Safety, 
M4E: The CTD  Efficacy): 
   Quality overall summary (2.3, Module 2, section 3) 
   Non clinical overview (2.4) 
   Clinical overview (2.5) 
   Nonclinical summary (2.6) 
   Clinical summary (2.7) 
The nonclinical summary and the clinical summary should be provided in separate 
volumes for ease of use by reviewers. 
C.  Module 3 - Quality 
Module 3 should include information on the drug or biological substance and product that 
should be provided in the order described below. See Appendix A for additional 
recommendations on the content and organization of module 3. 
1.  Module 3 table of contents 
The first document in this module should be a table of contents listing all of the 
documents provided for module 3.  See the guidance document M4Q: The CTD Quality 
for the headings and order to be used in the table of contents, including numbering of 
section headings. 
2.  Body of data 
Each individual subsection related to the drug or biological substance and product should 
be provided as an individual document either bound separately or divided by tab 
identifiers, depending on the size of the subsection.  The documents should be presented 
in the order in which they are listed in the table of contents. 
3.  Literature References 
Each literature reference should be provided as an individual document, separated from 
the others by tab identifiers. 
D.  Module 4 - Nonclinical Study Reports 
Module 4 should contain the nonclinical study reports and related information.  You 
should provide the documents for this module in the order described below. 
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1.  Module 4 table of contents 
The first document in this module should be a table of contents listing all of the 
documents provided for module 4.  See the guidance to industry M4S: The CTD  Safety 
for the headings and order to be used in the table of contents, including numbering of 
section headings. 
2.  Study reports and related information 
You should provide each study report and each related document as an individual 
document, separated from the other documents by binders or tab identifiers. These 
documents should be presented in the order in which they are listed in the table of 
contents. 
3.  Literature References 
Each literature reference should be provided as an individual document, separated from 
the others by tab dividers. 
E.  Module 5 - Clinical Study Reports 
Module 5 should contain clinical study reports and related information. You should 
provide the documents for this module in the order described below. 
1.  Module 5 table of contents 
The first document in this module should be a table of contents listing all of the 
documents provided in Module 5. See the guidance to industry M4E: The CTD - Efficacy 
for the headings and order to be used in the table of contents, including numbering of 
section headings. 
2.  Study reports and related information 
You should provide each study report and each related document, such as tabular listings 
of all clinical studies, as an individual document separated from the other documents by 
binders or tab dividers.  We recommend that tab identifiers be provided for each 
appendix in a study report.  These documents should be presented in the order in which 
they are listed in the table of contents. 
The submission of a separate ISE and/or ISS is not required when the information 
provided can be incorporated into the CTD summaries and overview.  When the ISS or 
ISE is submitted, it should be included in Module 5.3.5.3, Meta-Analyses.  The applicant 
should raise any questions concerning the ISS and ISE with FDA staff prior to 
submission of the application. 
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You should include any case report forms (CRF) as separate documents. The case report 
forms should be organized by study. 
The individual patient listings or case report tabulations (CRT) should include all of the 
clinical data collected in each study, organized by domain of data (e.g., adverse event, 
laboratory, physical examination). Each domain of data should be provided as a separate 
document. As with the CRFs, the CRTs should be organized by study. 
3.  Literature References 
Each literature reference should be provided as an individual document separated from 
the others by tab identifiers. 
IV.  GENERAL ISSUES FOR SUBMISSIONS 
Regulations in 21 CFR 314.50, 314.94, and 601.2 provide general requirements for submitting 
NDAs, ANDAs, and BLAs, respectively.  This section addresses briefly some general issues 
related to providing marketing applications in paper format.    
A.  Amendments and Supplements 
Although the CTD describes the agreed to common format for the preparation of the 
original application, you can use it for supplements to an original application or 
amendments to either the original application or subsequent supplements.  General 
correspondence should be included in Module 1. 
You can use the CTD format for submissions whether or not the previous submission was 
in the CTD format.  You should not mix the CTD and older formats in the same module. 
We will consider, on a case-by-case basis, accepting submissions where some modules 
are provided in the CTD format and the rest of the submission is not in the CTD format. 
You should discuss this possibility at the pre NDA/BLA meeting or earlier. 
B.  Organizing Documents 
You should bind all documents in separate volumes, or documents can be combined in 
volumes as long as they are separated by appropriately named tab identifiers. For 
example, the user fee cover sheet for a submission should be separated from the other 
documents by a tab identifier named user fee cover sheet. In general, documents from 
different CTD modules should not be included in the same volume.  You may want to 
combine documents from different modules in the same volume for amendments 
consisting of a small number of short documents. 
C.  Number of copies 
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The regulations require archival, review, and field copies of NDAs and ANDAs.  For 
BLAs, archival and review copies are generally submitted. The archival copy includes 
the entire submission.  The review and field copies require only a portion of the 
application (see below). 
1.  Archival copy 
The archival copy is a complete copy of the application.  It serves as the official archive 
of the application and may be used during the review of the application. 
2.  Review copy 
Review copies are in addition to the archival copy and include the information needed by 
each review discipline for its evaluation. These copies facilitate the concurrent review of 
the application by the different review disciplines.  Review copies that may be necessary 
according to 21 CFR 314.50 for an individual submission include: 
 	  Quality (Module 3), 
 	  Nonclinical (Module 4), 
 	  Clinical (Module 5) - safety and efficacy documents for clinical reviewer 
 	  Clinical (Module 5) - safety and efficacy documents for the statistical reviewer, 
 	  Clinical (Module 5) - clinical pharmacology and pharmacokinetics documents (or 
bioequivalence documents for ANDAs) , and 
 	  Clinical (Module 5)  clinical microbiology documents. 
You should include a copy of Modules 1 and 2 in each review copy.  Each review copy 
should be labeled and bound separately. 
It is recommended that you contact the office with the responsibility for the review of 
your product to determine how many copies of each module or sections of modules 
should be submitted. 
3.  Field copy 
The field copy should be a separately bound copy of the Quality section (Module 3) for 
the NDA and ANDA. You should send this copy directly to the appropriate field office. 
A field copy is not required for the BLA. 
D.  Paper size 
You should use standard U.S. letter size paper (8.5 x 11 inches) for all submissions. 
Occasionally, you may want to use individual pages larger than standard paper size to 
present a floor plan, synthesis diagram, batch formula, or manufacturing instructions. 
These pages should be folded and mounted so they may be opened for review without 
disassembling the jacket and refolded without damage when the volume is shelved. 
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E.  Paper margins 
We have found that a margin of at least 0.75 inches from the bound edge of the printed 
page prevents information from being obscured when the paper is placed in a binder. 
Other margins can be as small as 0.25 inches from the edge of the page.  You can submit 
documents printed on both sides of a page, provided legibility is not impaired and margin 
space is sufficient on both the left and right side, so that information is not obscured 
when the page is placed in a binder. 
F.  Fonts 
Font size for text and tables should be of a style and size that is large enough to be easily 
legible, even after photocopying or when provided electronically. We recommend that 
narrative text be submitted in Times New Roman 12 point font.  Generally, font sizes 9 to 
10 points are considered acceptable in tables, but you should avoid fonts smaller than 12 
points whenever possible.  When choosing a font size for tables, it is important to balance 
the desirability of providing sufficient information on a single page to facilitate data 
comparisons with that of maintaining a font size that remains readable.  If the font size is 
too large, data comparisons may be complicated because data may be presented in 
multiple tables. Ten point font is recommended for footnotes. 
G.  Binding volumes 
All pages should be submitted with three holes punched on the left side of the page and 
bound with fasteners, rather than placed in ring binders. 
We recommend using polyvinyl type binders (0.23 to 0.25 gauge) for the archival copies 
and extra heavy paper binders for the review and field copies.  A limited number of 
binders can be obtained by calling the number below.  The quantity that can be ordered at 
any one time is determined by the U.S. Government Printing Office (GPO). Additional 
information regarding binders may be obtained by accessing the FDA Internet site: 
http://www.fda.gov/cder/ddms/binders.htm. 
U. S. Government Printing Office 
Washington, D.C. 20404-0001 
(202) 512-1800 
Program #B511-S 
Additional binders can be purchased from commercial sources. 
The front cover of the binder should be 9 by 11.5 inches, and the back cover should be 9 
by 12 inches.  You should use colored binders to distinguish the different copies of the 
applications.  The archival copy should be blue.  For ANDAs, the review copy should be 
red.  For ANDAs and NDAs, the field copy should be green. The color for the NDA or 
BLA review copy binders depends on the type of information in the copy.  See Table 2 
for details. 
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Table 2: Binder Colors for NDA and BLA Review Copies 
Review copy for:  Binder color 
Quality  Red 
Nonclinical  Yellow 
Clinical- pharmacokinetics and bioavailability  Orange 
Clinical  microbiology  White 
Clinical - safety and efficacy - clinical  Tan 
Clinical - safety and efficacy  statistical  Green 
H.  Volume size 
Volumes should not be more than 2 inches thick.  Volumes thicker than 2 inches are 
difficult for both the document room personnel and reviewers to handle. 
I.  Volume numbering 
You should number the volumes by module, resulting in a separate set of numbers for 
each module. 
J.  Volume identification 
You should print the following information prominently in the central portion of the front 
cover of each volume: 
   Name of applicant 
   Name of product 
   Application number, if available 
   Module number and name 
On the front, lower right hand corner of each binder, you should print the volume number 
in the following format: x of y volumes where x is the number for the specific volume and 
y is the total number of volumes submitted for the respective module.  For example, 
volume 6 for the Safety module with a total of 50 volumes for the module would have 6 
of 50 volumes in the lower right hand corner.  The volumes in the module copy should be 
numbered sequentially. 
On the front, upper right hand corner, you should print Module __Volume ___.  You 
should fill in this blank for the initial submission of the application using the format 
Module m  Volume s.x, where m is the module number, s is the sequence number of the 
submission and x is the number of the specific volume in each module.  For example, if 
the first submission for an application is a chemistry presubmission, volume 15 of the 
presubmission would be named Module 3, Volume 1.15. 
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All copies of the submission, including the review copies, should use the same volume 
numbers.  However, the volume numbers may not be consecutive in the review copy 
since the review copy may only include a portion of the information in the archival copy. 
K.  Pagination 
Page numbering should be at the document level and not at the volume or module level. 
(The entire submission should never be numbered consecutively by page.)  In general, all 
documents should have page numbers.  Since the page numbering is at the document 
level, there should only be one set of page numbers for each document. 
If you include a document within a document, such as a protocol within a study report, 
the document to be included (in this case, the protocol) should be attached as an 
appendix.  You should demarcate each appendix with an appropriately named tab 
identifier.  For example, if the protocol is the first appendix, the tab should be named 
Appendix A or Protocol or some equivalent. 
L.  Cross referencing documents 
You should reference documents by volume, CTD module, tab identifier, and page 
number. 
M.  Packing carton 
To help us in storing submission volumes, we ask that you ship the volumes in boxes 
measuring 14 x 12 x 9.5 inches. On the outside of the carton, you should include the 
following information: 
 	  Applicants name 
 	  Drug/biologic name 
 	  Volume numbers included in the box 
 	  Boxes should be numbered 1 of n, 2 of n, 3 of n, and so on. 
 	  Type of copy included in the box (e.g., archival, clinical, safety, and efficacy review 
copy) 
N.  Sending the Submission 
1.  CBER 
Send all submissions to the Document Control Center (DCC). The address for the DCC 
can be found at the CBER web site at www.fda.gov/cber. 
2.  CDER 
For the NDA, you should send the initial paper submission to the central document room. 
You should send all other submissions to the appropriate division document room for 
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NDAs or, for ANDAs, to the Office of Generic Drugs. The addresses for the document 
rooms can be found at the CDER web site at www.fda.gov/cder. All submissions with 
electronic components should be sent to the central document room. 
V.  ELECTRONIC SUBMISSION 
We currently accept marketing applications in electronic format.  See the guidance Providing 
Regulatory Submissions in Electronic Format - General Considerations (January 1999), 
Providing Regulatory Submissions in Electronic Format  NDA (January 1999) and Providing 
Regulatory Submissions to the Center for Biologics Evaluation and Research (CBER) in 
Electronic Format - Biologics Marketing Applications (November 1999) for details on how to 
organize the documents for an electronic submission.  We will continue to accept marketing 
applications in this electronic format. 
ICH is working on guidance on providing an electronic CTD.  When we are ready to accept 
electronic CTDs, we will publish guidance on that process.  You can adapt the CTD to our 
current process for electronic submissions as described below. The table of contents files in the 
electronic submission should be the same as in a paper submission.  However, you should divide 
the table of contents as described in the Providing Regulatory Submissions in Electronic Format 
guidance documents so each folder in the electronic submission has a table of contents as 
follows: 
 	  Summary table of contents - you can place all of the Module 2 summary documents in the 
summary folder and use the Module 2 table of contents 
 	  Quality table of contents - you can use the Module 3 table of contents in place of the CMC 
table of contents 
 	  Clinical table of contents - you can divide the table of contents for the clinical study reports 
into one for the human pharmacology and bioavailability/ bioequivalence studies; one for 
microbiology study reports, if applicable; one for the efficacy and safety studies; one for 
CRTs; and one for CRFs. The tabular listing for all clinical studies should be included in 
table of contents for all study reports. 
VI.  QUESTIONS ABOUT PREPARING AND SENDING SUBMISSIONS
 A.  CBER 
Send an email to cber@fda.gov with questions concerning paper submissions and 
esubprep@cber.fda.gov with questions concerning electronic submissions. 
B.  CDER 
Send an email to cder@fda.gov with questions concerning paper submissions and 
esub@cder.fda.gov with questions concerning electronic submissions. 
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APPENDIX A:  CONTENT OF THE CTD 
The following table lists guidances and other publications relevant to the content of the modules 
in the CTD.  All FDA and ICH guidance documents are available on the Internet at 
www.fda.gov/cder/regulatory/guidance/index.htm and www.fda.gov/cber/guidelines.htm, for 
CDER and CBER, respectively. 
Module  Refer to Other Guidance Documents 
General  See FDA Form 356h 
Information 
on the 
content of a 
submission 
Module 1  Submitting Applications According to the ICH/CTD Format -
General Considerations (this guidance) 
Module 2  See ICH guidances. 
Module 3  Drug or biological substance and product guidance documents 
- Drug Product: Format and Content for Submission of New Drug 
Applications (NDAs) and Abbreviated New Drug Applications 
(ANDAs) Drug Substance 
- Refer also to the regulations at  21 CFR 314.94 
Specific subjects like botanicals, metered dose inhalers and nasal 
products, packaging, and stability are addressed in topic specific 
guidances 
Module 4  See M2 ICH guidances. 
See also ICH guidances S1A and S4. 
Module 5  Integrated summary of safety section 
- Guideline for the Format and Content of the Clinical and 
Statistical Sections of an Application, July 1988, page 32 to 46 
Integrated summary of efficacy section 
- Guideline for the Format and Content of the Clinical and 
Statistical Sections of an Application, July 1988, page 28 to 32 
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APPENDIX B:  REGULATORY REQUIREMENTS AND THE CTD 
No changes in regulations are needed to implement the CTD guidelines. The following table lists 
the location of regulatory requirements in relationship to the CTD modules. 
CTD  NDA: 314.50  ANDA: 314.94  BLA: 601.2 
(unless otherwise  (unless otherwise 
indicated)  indicated) 
Module 1  (a) application form  (a)(1)application  (a) application form 
form 
(c)(2)(i) annotated  (a)(2) table of 
text  of proposed  contents 
labeling 
(d)(1)(v) statement  (a)(3) basis for 
of field copy  ANDA submission 
(e) samples and  (a)(4) conditions of  (a) Labels, 
labeling  use  enclosures and 
medication guides 
(h) patent  (a)(5) active  306(k)(1) and (2) 
information  ingredients  debarment certifica-
tion/list of convict-
ions (FDC Act) 
(i) patent  Section 306(k)(1) 
certification  and (2) debarment 
certification/list of 
convictions (FDC 
Act) 
(j) claimed  (a)(6) route of 
exclusivity  administration, 
dosage form and 
strength 
(k) financial  (a)(8) labeling 
certification or  requirements 
disclosure 
(a)(12) patent 
certification 
(a)(13) financial  (a) financial 
certifications or  certification or 
disclosure statement  disclosure statement 
(d)(5) certification  (a) claim of 
of field copy  categorical 
exclusion or 
environmental 
assessment 
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Module 2  (b) comprehensive  N/A 
table of contents 
(c) summaries  (a) summaries 
(d)(5)(vii) abuse 
potential 
Module 3  (d)(1) cmc  (a)(9) cmc  (a) full description 
of manufacturing 
methods 
(a)(10) samples  (a) samples 
Module 4  (d)(2) nonclinical  N/A  (a) data from non-
pharmtox  clinical studies 
Module 5  (d)(3) human  (a)(7)bioequivalenc 
pharmacokinetics  e/bioavailability 
information 
(d)(4) microbiology  320.22(d)(2)(i) 
waiver of in vivo 
BA/BE 
(d)(5) clinical data  (a) data from 
clinical studies 
(d)(6) statistical 
section 
(d)(7) pediatric use 
(f) CRF and CRT 
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