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DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only.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publication of the Federal Register notice announcing the availability of the draft guidance.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
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

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.

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.
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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:

• Applicant’s 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

Information

on the

content of a

submission

See FDA Form 356h

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
Draft — Not for Implementation

1

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

(unless otherwise

indicated)

BLA: 601.2

(unless otherwise

indicated)

Module 1 (a) application form (a)(1)application

form

(a) application form

(c)(2)(i) annotated

text of proposed

labeling

(a)(2) table of

contents

(d)(1)(v) statement

of field copy

(a)(3) basis for

ANDA submission

(e) samples and

labeling

(a)(4) conditions of

use

(a) Labels,

enclosures and

medication guides

(h) patent

information

(a)(5) active

ingredients

306(k)(1) and (2)

debarment certification/list of convictions (FDC Act)

(i) patent

certification

Section 306(k)(1)

and (2) debarment

certification/list of

convictions (FDC

Act)

(j) claimed

exclusivity

(a)(6) route of

administration,

dosage form and

strength

(k) financial

certification or

disclosure

(a)(8) labeling

requirements

(a)(12) patent

certification

(a)(13) financial

certifications or

disclosure statement

(a) financial

certification or

disclosure statement

(d)(5) certification

of field copy

(a) claim of

categorical

exclusion or

environmental

assessment
Draft — Not for Implementation

2

Module 2 (b) comprehensive

table of contents

N/A

(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

pharmtox

N/A (a) data from nonclinical studies

Module 5 (d)(3) human

pharmacokinetics

(a)(7)bioequivalenc

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