Last Update : November 11, 2003

CTD General Questions and Answers

Date of Questions Answers
Approval
1 Sept. Format or Content?
2002 Will a dossier using the CTD format (Modules 2 to 5) be identical Not necessarily.
for all regions? The CTD provides a common format for the submission of
information to regulatory authorities in the three ICH regions.
However, the CTD does not address the content of submissions.
There are many regional requirements, as well as applicants’
preferences, that could affect the contents of dossiers submitted
in each region.

2 Sept. Expert Reports

2002 Are expert reports still required for submissions under the CTD No. Expert Reports are replaced by Module 2.
format? (N.B. For specific European requirements regarding experts’
signatures, please refer to the European Commission Web Site.)

3 Sept. Tables of Contents and Pagination

2002 For a paper CTD submission, the guideline states that, for the There are no specific guidelines for the page numbers of the
comprehensive Table of Contents in module 1, no page numbers TOC.
should be used. Does this apply only to the TOC in module 1, or for Module numbers, volume numbers, and tab dividers should be
all TOCs in every module? Also, besides the volume numbers and part of all TOC’s.
tab identifiers, should the module numbers also be included? For
modules 3, 4, and 5, should the volume number be part of the Table
of Contents?

4 Sept. How to paginate Literature References

2002 When provided, how should literature references be paginated in a Literature References should be paginated according to the page
paper CTD? Should each reference start with page 1, or should the numbering of the source (journal, abstract, etc).
page number from the source (journal, abstract, etc) be the only page
number included?

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 Last Update : November 11, 2003

CTD General Questions and Answers

Date of Questions Answers
Approval
5 Sept. Sub-Heading Numbering, or Numbering Within Sections
2002 How should sub-numbering within a document be organised? Some Within the document, the applicant can use section numbers at a
documents can be up to 50 pages in length with no defined CTD lower level than those specified in the CTD guideline. However,
guideline heading, and potentially therefore no TOC entries or there should be no other headings appearing in the overall TOC
bookmarks (in the electronic version). Some guidance would be going below the numbering given in the CTD guideline.
welcome to avoid regional interpretations on what is considered
acceptable. For example, for section 3.2.P.3.3 it would be possible to use
subsequent numbers (3.2.P.3.3.1, 3.2.P.3.3.2, etc.) to provide
further navigation within the document. These should not
appear in the overall TOC but can be included as bookmarks
within the PDF files.

6 Sept. Titles of Documents Within Sections (e.g. reports etc.)

2002 In the header or footer of each document in a dossier the appropriate It is recommended that a distinct identifier be put in
TOC title entry should be included. In case of e.g. a clinical report headers/footers on every page. However, it does not need to be
the TOC entry is the title of the report and this can be really long. the full title. An abbreviation would suffice.
Would the use of the report number (alone) be considered sufficient?
In other words, can the layout of the pages throughout the dossier be
different: one page layout for reports and another one for Quality
sections?
∗
7 Rev Cross references / Cross Strings (in Paper Submissions)
Nov. It is stated in the CTD that the section should be indicated in cross Providing the section header in addition to the section number
2003 strings. What is meant here: The section number, or the section improves the clarity of the reference, particularly for the
number and section name? (The section name is in many cases too uninitiated reader. To reduce the length of the cross string while
long to indicate in a cross string.) maintaining the ease of use, it is recommended to include only
the section number in the cross string and write the text so the

∗
Rev. = Revised

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 Last Update : November 11, 2003

CTD General Questions and Answers

Date of Questions Answers
Approval
reader will also know the section content. For example, “…as
seen in the population PK study 101 (5.3.3.5)” helps the reader
to find the referenced study report under the Population PK
Study Reports section. The text “…no safety problems were
noted in the uncontrolled pneumonia study 101A (5.3.5.2)” helps
the reader find the referenced study report under the section
Study Reports of Uncontrolled Clinical Studies for the
Pneumonia indication.

8 Sept. General Glossary of Terms

2002 Will there be a general glossary of recommended terminology for No glossary of terms is planned at this time.
use in the CTD?
9 Sept. Location of the Information on Biological Comparability
2002 A combined comparability section might be beneficial to the review No, for the moment the CTD does not foresee any separate
process. Is it possible to consider a modification to the CTD to section combining all the comparability data.
provide for such a section for Biological products?
N.B. Currently, comparability data should be included under
2.3.S.2/3; preclinically as proposed; and clinically under 2.5.2 and
2.5.6. Each part should summarise briefly the conclusions from the
other sections.
- in the clinical summary, antigenicity should go under either
2.7.4.3 or 2.7.4.4
- in the clinical summary, "AEs of special interest" and "Mortality
and Hospital Re-admission" should go under 2.7.4.2.1.4 (Other
significant AEs).

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 Last Update : November 11, 2003

CTD General Questions and Answers

Date of Questions Answers
Approval
10 Sept. Information for Generic Drug Applications The CTD provides a format for the submission of information to
2002 Should the preclinical and clinical summary sections of the CTD be regulatory authorities. It does not define content. Please refer to
included in applications for generic drug approvals? More region-specific requirements to determine content requirements
specifically, are Module 4 and 5 of the CTD applicable to for the specific submission type.
Abbreviated New Drug Applications (ANDA) in the US and
Abridged Marketing Authorization applications in the EU? Both
categories of applications apply to generic drug applications, which
ordinarily provide preclinical and clinical data based on available
literature.
11 June Font style
2003 On the basis of corporate identity we use the font style "Arial" for all “Times New Roman 12 point” is recommended for use in the
of our documents. CTD. This corresponds to MS Mincho, 10.5 point for the text
Can we use the font style "Arial" for CTD´s, or do we have to use written in Japanese.
"Times New Roman" style to match the recommendation for
narrative texts according to the Guidance for Industry "Organisation
of the CTD"?
12 June Language
2003 Can the CTD be in any language (e.g. Japanese, German, French, The CTD does not address this issue.
English)? Is it limited to a single language? Please refer to regional guidance.
13 June Changes of numbering and section headers
2003 With regard to the changes regarding numbering and section headers These changes in recommendation apply to all CTD/eCTD
submissions.
(September 11-12,2002), are the details in brackets (e.g. name,
manufacturer or name, dosage form) only for use in eCTD format or
for paper files also?

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 Last Update : November 11, 2003

CTD General Questions and Answers

Date of Questions Answers
Approval
Headers and page numbering
What is your guidance for externally produced documents e.g. Please refer to the CTD General Q&As No. 5 on the ICH Web
chromatograms, CTD format DMF, regarding page numbering and site.
appropriate headers? Are there allowances regarding these
documents with regard to pagination and headers i.e. are we allowed
to submit them in the relevant document without a header or page
number?
Tab
Do Tabs have to be printed? Do we have to use the full title with the Tabs should be printed for a paper submission.
number string on the tab? This is very difficult if the title is long. Tab abbreviations are acceptable.
14 July Is there a difference in the level of analysis in the non-clinical Please refer to the general guidance for both the non-clinical and
2003 overview and the clinical overview in Module 2? Is there a clinical overviews. The level of analysis does not differ between
difference between “critical analysis” (non-clinical overview) and these two overviews. The guidance describes the information
“critical assessment” (clinical overview). that should be included in the “critical and integral”
assessment/analysis in both overviews.
15 July Is the term, “section”, defined in the CTD? Is there a different use of Each section in the CTD is identified by a number and a heading
2003 the term in Module 2 and 3? Do the ICH regions define sections Please refer to the Granularity Document Annex for a
differently? description documents to be provided in each section. The
annex delineates when multiple documents per heading may be
provided. Also, refer to regional guidance as to when one or
multiple documents should be provided per heading.
16 July Does the deadline for mandatory submission of the CTD in Japan, The deadline does not refer to the eCTD although the regulatory
2003 the EU and the US (highly recommended in the US) also refer to the authorities are accepting eCTD submissions. Please refer to
eCTD? regional guidance for specific guidance on eCTD submissions.
Has ICH considered planning a seminar to help with CTD and eCTD Currently the ICH is not planning to conduct a CTD seminar.
submissions? However, the ICH6 Conference, November 2003 in Osaka
Japan, will focus on the CTD and eCTD.
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 Last Update : November 11, 2003

CTD General Questions and Answers

Date of Questions Answers
Approval
17 July Has the DTD reached its final stage of approval in the ICH process? The eCTD DTD has reached step 5 in the ICH process, which is
2003 the implementation step.
18 July Is there a definition of which attachments should be included in the It is not suggested that additional attachments be included in the
2003 CTD? CTD.
19 Nov. CTD training No, there are no general ICH recommendations for training on
2003 Does ICH recommend any particular comprehensive training course CTD implementation.
on the implementation of the CTD?
20 Nov. Applicant’s Logo
2003 Is it allowed to add the Applicant's Logo either on top of the CTD, or The applicant is free to put his logo on top of the CTD.
However, logos are not acceptable in CTD sections' titles. (The
in the titles of CTD sections.
latter have been harmonized internationally; therefore applicants
are not allowed to modify them.)
21 Nov. Herbal CTD ICH does not plan to issue any specific version of the CTD for
2003 Will a Herbal Products version of the CTD be published and how Herbal Products.
much will it vary from the pharmaceutical CTD.
22 Nov. Granularity: section headings and numbers, documents Please refer to the Annex of the Organisation of the Common
2003 location/hierarchy, documents pagination Technical Document: "Granularity Document".
The CTD specifies many section headings and numbers. Could
guidance be provided for all modules on headings in relation to
document location and the section headings within those documents?
Could guidance also be provided on where in the CTD and eCTD
multiple documents can be located in the hierarchy?
As a consequence of this definition could guidance be given on how
documents should be paginated and on what the module Table of
Contents should therefore include?

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 Last update : November 11, 2003

CTD-Safety Questions and Answers

Date of Questions Answers
Approval
1 May Kinetics in Pregnant Animals and Neonates
2001 Kinetics in pregnant animals and neonates are included in the The CTD-S guideline is not intended to indicate what studies are
PK section. Is it expected that these data will come from PK required. It merely indicates an appropriate format for the nonclinical
studies, or can they be from kinetics in the Segment 2 studies? data that have been acquired.

2 Sept Conduct/Non-Conduct of Specific Studies

2002 If a particular category of toxicology studies (e.g. Section headings should be maintained in the CTD document and a
carcinogenicity) is not conducted for a drug because of the brief explanation provided as to why these studies were not conducted.
nature of the drug (e.g. oncology agent), should the section
heading be maintained in the CTD document with an
explanation provided as to why these studies were not
conducted, or should the heading section be deleted and
subsequent sections renumbered?

3 Sept Pivotal Studies

2002 Would a 3-month toxicity study that was needed to support Yes. There should be one table for each of the repeat-dose toxicity
clinical studies of 3-month's duration, that was later replaced studies specified by ICH Guideline M3, as well as any other repeat-
with a 9-month toxicity study, be considered "pivotal" and dose toxicity studies that could be considered pivotal.
tabulated as in Table 2.6.7.7?

4 Sept Tabulated Summary

2002 Are only toxicologically significant changes, as considered by Only noteworthy findings should be tabulated in CTD. These might
applicants, to be tabulated in CTD? include statistically significant differences from controls, as well as
noteworthy findings that are not statistically significant.

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 Last update : November 11, 2003

CTD-Safety Questions and Answers

Date of Questions Answers
Approval
5 Sept Impurity Data Table in CTD-Safety – 1
2002 Generally speaking, it is unlikely to have the finalized One purpose of the "Drug Substance" table is to facilitate a review of
specification for related substances and their analytical method the qualification of the specified impurities. If the analytical methods
throughout drug development. Therefore, direct comparison of have changed, information on early batches may not be applicable for
related-substance data between different stages of development qualification of impurities. In this case, it is recommended to use
would be very difficult, because of analytical method changes. footnotes in the "Drug Substance" table to identify the batches that are
relevant to qualification of impurities.

6 Sept Impurity Data Table in CTD-Safety – 2

2002 Should impurity-specification test results of test articles used There is no requirement to analyze the drug substance used in non-
in early-stage toxicology studies be included in CTD tables? GLP studies. However, if such analyses have been conducted, the
Do test articles of non-GLP studies in the CTD need to have results should be included in the "Drug Substance" table.
specification test data?

7 Sept Nonclinical Tabulated Summaries Templates

2002 Are the templates for the nonclinical tabulated summaries It is recommended that summary tables for the nonclinical information
(module 2.6) a suggested or a required format? in the Common Technical Document be provided in the format
outlined. Applicants can modify the format if needed to provide the
best possible presentation of the information and to facilitate the
understanding and evaluation of the results.

8 Sept List of References

2002 A section for list of references of the nonclinical summary Applicants can place the list of references in the most appropriate
(2.6.8 or 2.6.2.8 plus 2.6.4.11 plus 2.6.6.11) is not covered in location and create new subsection numbers as far as it facilitates the
the guidance, unlike for the clinical summary and both best possible understanding by the regulatory reviewers.
nonclinical and clinical overview. Could you please provide
clarity where in these summaries lists of references should be
included?

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CTD-Safety Questions and Answers

Date of Questions Answers
Approval

9 Feb Nonclinical pharmacokinetics In such a case, the sponsor could either put that study report in the first
2003 place in the CTD module (i.e., Absorption section) and then cross
A number of studies in nonclinical pharmacokinetics could
reference to this study report in the remaining sections, or place the
appear more than one place in this section.
full study report in each adequate section.
Should we add nonclinical pharmacokinetic studies to all
Pharmacokinetics sections? If submitting an e-CTD, a sponsor needs not submit multiple files are
not required. References to the one file should be provided.
10 *Rev. Microbiology data The Microbiology data from both in vitro and in vivo studies should
Nov The microbiology data will include both in vitro and in vivo be included with the Efficacy information. The summary information
2003 studies. Where should the microbiology summary, overview should be provided in the appropriate section 2.7 Clinical Summary
and study reports be included? and the reports should be filed in section 5.3.5.4 Other Study Reports.
In addition, the microbiology information can be described in the
Nonclinical sections as appropriate.
11 July The template for local tolerances (2.6.7.16) in M4S does not The template for 2.6.7.16 is the same as the template for 2.6.7.17.
2003 provide an example of a tabulated summary of a local Therefore for an example of 2.6.7.16, please refer to the example of
tolerance. Is there one available? 2.6.7.17.

12 July In the development of human monoclonal antibodies, part of Applicants can place such studies in the most appropriate location in
2003 the nonclinical development is to perform 2 cross reactivity Module 4 in order to facilitate the best possible understanding by the
studies; 1) animal species cross reactivity study and 2) human regulatory reviewers. ( This can be the similar answer to the Question
tissue cross reactivity study. #8 )
The animal species cross reactivity test is not really a toxicity
study, and the human tissue cross reactivity study is not a
study generally performed. We are in doubt where to place
these in module 4. Where should these studies be placed in
module 4? Under 4.2.3.7 Other toxicity studies?

* Rev. = Revised 3
 Last update : November 11, 2003

CTD-Efficacy Questions and Answers

Date of Questions Answers
Approval
1 Feb Clinical study reports contained in Module 5 are cited in the Clinical We recommend that each study have a unique short identifier
2002 Overview and/or the Clinical Summary in Module 2. Each clinical that is used consistently throughout the application. The
study report may be given a unique short name when cited. Does applicant can select the identifier. The full title of the study is
the method of citing and naming have to be uniform throughout provided in the Tabular Listing of All Clinical Studies (Section
all modules? 5.2).

2 Sept Definitions/Terminology Guidance is provided by ICH E3 Guideline.

2002 What is the definition of 'Common Adverse Events' as used in the
CTD?

3 Sept Section Numbering/Title (in Module 5) See ICH Granularity document.

2002 In the module 5 of the CTD, is it necessary to have a section number
for each clinical study report in a certain section, or is it enough just
to mention the title:
5.3.5 Reports of Efficacy...
5.3.5.1 Study Reports....
5.3.5.1.1 Placebo Controlled....
Study XXX

4 Feb How many pages should a Clinical Summary be for an The estimated size of this document is 50-400 pages, assuming
2002 application that contains multiple indications? (Section 2.7) one indication. Applications that include multiple indications
will be larger, reflecting the submission of multiple efficacy
sections.

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 Last update : November 11, 2003

CTD-Efficacy Questions and Answers

Date of Questions Answers
Approval
5 Feb Section “2.7.3.3” Comparisons and Analyses of Results Across
2002 Studies
The Guideline provides “This section should also cross-reference Section 2.7.3.3 summarizes the data across all studies that
important evidence from Section 2, such as data that supports the characterize efficacy of the drug; Section 2.7.3.4 provides an
dosage and administration section of the labeling.” However, this integrated summary of the dose-response or blood concentration-
Guideline also provides a Section, “2.7.3.4. Analysis of Clinical response relationships of effectiveness. In both cases, supportive
Information Relevant to Recommended Dose.” Please specify how data from Section 2.7.2 can also be incorporated.
to differentiate the two sections “2.7.3.3” and “2.7.3.4”.
6 Feb Overall Extent of Exposure (Section 2.7)
2002 In the Guideline, a table is required to be generated to present the The table should refer to all subjects exposed to at least one dose
overall extent of drug exposure in all phases of the clinical of the drug product. Appropriate subsets of subjects relevant to
development. Should the table include “patients alone” or “patients the proposed indications should also be identified and
and healthy subjects”? considered.

7 Feb Summary of Clinical Safety (Section 2.7)

2002 Where should information be described concerning the validity of Summaries of any bridging studies using clinical endpoints (i.e.,
extrapolation of foreign clinical safety data to a new region? certain studies intended to evaluate the ability to extrapolate
certain types of foreign clinical data to the new region (see ICH
E5)) should be included in Section 2.7.3.2. Where appropriate,
such information should also be described in the summarization
of safety data as related to intrinsic and extrinsic ethnic factors
(ICH E5), in Sections 2.7.4.5.1 and 2.7.4.5.2. Finally, some
applications might include in Section 5.3.5.3 a detailed analysis
of bridging, considering formal bridging studies, other relevant
clinical studies, and other appropriate information. Such
information should be included in that detailed analysis of
bridging.

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 Last update : November 11, 2003

CTD-Efficacy Questions and Answers

Date of Questions Answers
Approval
8 Sept Bioavailability/Bioequivalence Study Data (Module 5)
2002 Where should the information on bioequivalence studies for a Bioavailability study reports should be included in Module 5
generic application be included? (Clinical documentation), under section 5.3.1 “Reports of
Biopharmaceutical Studies”. More specifically, reports of
comparative Bioavailability/Bioequivalence studies should go
under section 5.3.1.2.

9 Sept Tabular Listing of Clinical Studies in Paper CTD

2002 In module 5, 5.2 is denoted as the ‘Tabular Listing of all Clinical The tabular listing described in section 5.2 is a listing of all
Studies’. Is this section for a summary listing of all clinical studies clinical studies in the submission.
in the submission, or it is for the listings of the individual study
reports? In other words, should the listings from the appendices of An example of such a listing is given in Table 5.1.
the individual study reports be included here, rather than as an
appendix to the CSR, or are these only listings that summarize all
studies?

10 Feb ISS/ISE
2003 Does the CTD section on safety in Module 2 replace the section The ISS/ISE are critical components of the safety and
under 21 CFR 314.50(d)(5)(v, vi) calling for integrated summary of effectiveness submission and are expected to be submitted in the
safety and effectiveness (ISS/ISE)? application in accordance with the regulation. FDA’s Guideline
for the Format and Content of Clinical and Statistical Sections of
Application gives advice on how to construct these summaries.
Note that, despite the name, these are integrated analyses of all
relevant data, not summaries.
The Clinical Safety sections of the CTD follow approximately
the outline of the sections of the ISS/ISE, although they are
somewhat modified by experience with ICH E-3 (Structure and
Content of Clinical Study Reports). The CTD Clinical
Overview and Summary in Module 2 will not usually contain the
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 Last update : November 11, 2003

CTD-Efficacy Questions and Answers

Date of Questions Answers
Approval
level of detail expected for an ISS. It may contain the level of
detail needed for an ISE, but this would need to be determined
on a case-by-case basis.
If, the requirements of 21 CFR 314.50 can be met for a particular
application by what is in the CTD Module 2 summary, then the
CTD Module 2 section would fulfill the need for an ISS/ISE. In
some cases it will be convenient to write much of what is needed
in the CTD Module 2 with appropriate appendices in Module 5.
In other cases, the ISS/ISE would be summarized in Module 2,
with detailed reports in Module 5.
Any questions about these matters can be raised with the
reviewing division.
11 Nov. Microbiology data
2003 The microbiology data will include both in vitro and in vivo studies. The Microbiology data from both in vitro and in vivo studies
Where should the microbiology summary, overview and study should be included with the Efficacy information. The summary
reports be included? information should be provided in the appropriate section 2.7
Clinical Summary and the reports should be filed in section
5.3.5.4 Other Study Reports.
In addition, the microbiology information can be described in the
Nonclinical sections as appropriate.

12 Nov. Clinical variation

2003 For a clinical variation application, is it mandatory to submit a Since variation is a term from the EU regulations, the answer
clinical overview and a clinical summary, or is it acceptable to should be provided by the EMEA.
submit either only an overview or only a summary? What are the
parameters/conditions to be taken into account for choosing one or
the other approach?

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 Last update : November 11, 2003

CTD-Efficacy Questions and Answers

Date of Questions Answers
Approval
13 Nov. Integrated analysis of efficacy (ISE) - Section 2.7 Clinical
2003 Summary – Statistical Listings As stated in section Reports of Analyses From More Than One
What approach should applicants take for the formatting and Study 5.3.5.3, where the details of the analysis are too extensive
presentation of their integrated analyses when they have large to be reported in a summary document, for example, section
amounts of statistical output to present (several thousands of pages)? Clinical Summary 2.7, they should be presented in a separate
report. Such report should be placed in section 5.3.5.3.
14 Nov. Cross references / Cross Strings (in Paper Submissions)
2003 It is stated in the CTD that the section should be indicated in cross Providing the section header in addition to the section number
strings. What is meant here: The section number, or the section improves the clarity of the reference, particularly for the
number and section name? (The section name is in many cases too uninitiated reader. To reduce the length of the cross string while
long to indicate in a cross string.) maintaining the ease of use, it is recommended to include only
the section number in the cross string and write the text so the
reader will also know the section content. For example, “…as
seen in the population PK study 101 (5.3.3.5)” helps the reader
to find the referenced study report under the Population PK
Study Reports section. The text “…no safety problems were
noted in the uncontrolled pneumonia study 101A (5.3.5.2)” helps
the reader find the referenced study report under the section
Study Reports of Uncontrolled Clinical Studies for the
Pneumonia indication.
15 Nov. Limitations of the Safety Database and Potential Implications
2003 Section 2.5 Clinical Overview and section 2.5.5 Overview of Safety A fuller discussion of how to describe in the CTD the limitations
both refer to an assessment of the limitations of the safety database of the safety database and the potential implications for the
but give few details on how to describe them. How should these safety of the drug when marketed is as follows:
limitations be described? In addition, there is no specific reference to
• Nonclinical toxicology and safety pharmacology concerns,
any postmarketing steps the applicant can take to remedy those
such as those arising from reproductive / developmental
limitations. Where should a discussion of any postmarketing
toxicity, carcinogenicity, hepatic injury, central nervous
pharmacovigilance and other postmarketing study plans go?
system injury, or effects on cardiac repolarization that are not
fully resolved by available human data, or that arise from
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CTD-Efficacy Questions and Answers

Date of Questions Answers
Approval
incomplete testing.
• Limitations of human safety database, such as:
o Patient selection criteria that excluded people who are
likely to be candidates for treatment in medical practice.
o Evaluations that were deficient for certain purposes (e.g.,
many drugs with sedative properties are not evaluated for
effects on cognitive function in the elderly).
o Limited exposure of demographic or other subgroups,
such as children, women, the elderly, or patients with
abnormal hepatic or renal function.
• Identified adverse events and potential adverse events that
require further characterization or evaluation with respect to
frequency and/or seriousness in the general population or in
specific subgroups.
• Important potential risks (e.g., known risks of
pharmacologically related drugs) that require further
evaluation.
• Drug-drug interactions that have not been assessed
adequately.
Such information should be described and discussed in section
2.5.5 Overview of Safety, with appropriate cross references to
section 2.7.4 Summary of Clinical Safety and any other relevant
sections.
A discussion of any planned postmarketing activity or study to
address the limitations of the premarketing safety database,
should also be included in section 2.5.5 Overview of Safety,
with any protocols for specific studies provided in section
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CTD-Efficacy Questions and Answers

Date of Questions Answers
Approval
5.3.5.4 Other Clinical Study Reports or other sections as
appropriate (e.g., module 4 if the study is a nonclinical study).
An ICH guideline (E2E Pharmacovigilance Planning) is being
developed to further address the question of how to describe the
safety data and its limitations and how to describe planned
postmarketing activities and studies.
16 Nov. Multiple Indications
2003 When submitting one dossier for multiple indications, how should One section 2.5 Clinical Overview is recommended for multiple
the applicant present them in the clinical part of the registration indications to be registered along with development rationale
dossier, for example sections 2.5 Clinical Overview, 2.7.3 Summary and cross-referencing to the corresponding 2.7.3 and 5.3.5
of Clinical Efficacy and 5.3.5 Reports of Efficacy and Safety sections; the “benefit/risk” conclusions should support
Studies? corresponding claimed indications.
For section 2.7.3 Summary of Clinical Efficacy, in the case of
more than one indication, the following organization is
recommended as applicable. The current CTD numbering should
be retained with identification of the indication, for example:
2.7.3.UTI Summary of Clinical Efficacy
2.7.3.1.UTI Background
2.7.3.2. UTI Summary of Results of individual studies
2.7.3.3. UTI comparison and analysis
2.7.3.3.1. UTI study population
2.7.3.3.2. UTI Comparison of efficacy results
2.7.3. Pneumonia Summary of Clinical Efficacy
2.7.3.1. Pneumonia Background
Other sections follow the same organization where applicable.
For section 5.3.5 Reports of Efficacy and Safety Studies, in case
of more than one indication, the following organization is
recommended as applicable. The current CTD numbering should
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CTD-Efficacy Questions and Answers

Date of Questions Answers
Approval
be retained with identification of the indications, for example:
5.3.5.UTI
5.3.5.1. UTI Controlled studies
5.3.5.2. UTI Uncontrolled studies
5.3.5. Pneumonia
5.3.5.1. Pneumonia Controlled studies
5.3.5.2. Pneumonia Uncontrolled studies
Other sections follow the same organization, where applicable.
17 Nov. Narrative descriptions
2003 The CTD guidance for Section Overall Safety Evaluation Plan and In general, safety results should be described in section 2.7.4.1.1,
Narratives of Safety Studies 2.7.4.1.1 states that narrative because section Summary of Clinical Efficacy 2.7.3 is devoted
descriptions for studies that contributed both efficacy and safety to efficacy. To avoid the need to describe the same study twice,
should be included in Section Summary of Results of Individual section 2.7.3.2 asks for a reasonably complete description of
Studies 2.7.3.2 and only referenced in the safety section. Please studies pertinent to both safety and efficacy, including, in study
clarify whether the narrative to be included in 2.7.3.2 should include narratives, information about the extent of exposure of study
the safety results as well as “enough detail to allow the reviewer to subjects to the test drug and how safety data were collected.
understand the exposure… and how safety data were collected” or This approach is confirmed in section 2.7.4.1.1, which notes that
whether the results should be included in Section 2.7.4.1.1. narratives for studies contributing both safety and efficacy data
should be included in section 2.7.3.2. As noted in section
Background and Overview of Clinical Efficacy 2.7.3.1, however,
any results of these studies that are pertinent to evaluation of
safety should be discussed in section Summary of Clinical
Safety 2.7.4.