Common Technical Document

(CTD)

Dr Pravina
ICRI
 What is the CTD?

The CTD refers to an application format

and not to an application type

• The CTD is a prescribed organization of

the information required to be submitted.

• CTD is a DOSSIER/RESEARCH BINDER

for regulatory submission for marketing
approval of a drug
 CTD helps in
CTD does not indicate the studies
required to support the application; it
merely indicates an appropriate format for
the representation of chemical-
pharmaceutical, nonclinical and clinical
data that have been acquired.
 CTD Objectives
1) To provide a common format for the
preparation of technical documentation to
support a Marketing Authorization Application
(i.e. a new drug application) that will be
submitted to the regulatory authorities.
2) Possibility of simultaneous filings in the ICH
regions
• Reduce the time and resources needed to
compile i.e. Eliminates the extensive work of
rewriting/converting a dossier for different regulatory
submissions
 CTD Objectives
4) Regulatory reviews and communication
with the applicant will be facilitated by a
standard document of common elements.
5) Exchange of regulatory information
between Regulatory Authorities will be
simplified.
 What is the current status
of the CTD?
Nov 2000 meeting of the ICH Steering
Committee in San Diego – Step 4 status of CTD
guideline
Deficiency of formatting and integration of the components
(modules) of the CTD

May 2001 ICH meeting in Tokyo, agreement

was reached on a set of principles for the
uniform formatting of the CTD.

Sept 2002 - Inclusion of the Granularity

Document as Annex.
 What is the current status
of the CTD?
Current Step 4 version M4 (R3)

January 2004

Applications for all new pharmaceuticals

(including biotechnology-derived products)
 Functionality of CTD
The CTD does not harmonise the
technical content of the submission it
simply provides a common format in which
the data must be submitted. Therefore it is
necessary to complete development
programs that address regional
requirements and include those within the
CTD format.
 Is CTD format mandatory?
Implementation within the three ICH
regions
Yes : Europe
Japan

(July 2003)
 USFDA & CTD
On October 16, 2001, FDA electronically
published the CTD as formatted in May (Notice
of Availability published in FR), after having
been reviewed for compliance with GGPs.

FDA publishes the document as a guidance in

the Federal Register per Good Guidance
Practices (GGPs) and thereby formally adopts
the ICH guideline as an FDA guidance
 USFDA
CDER --------- NDA

CBER ---------BLA

• Form 356h
 BLA
No final CTD format

• no regulatory impediment to accepting a

BLA that follows the CTD format, as long
as the content meets CBER's
requirements.
 CTD guidance document

No of documents:

M4O - Organization
M4Q - Quality
M4S - Safety
M4E - Efficacy

eCTD – electronic version of CTD

Total pages 200

 CTD Modules
No. of modules : 5

* Module 1 - Regional Information

* Module 2 – Quality overall summary
Nonclinical overview
Clinical overview
Nonclinical written summaries
Clinical summaries
* Module 3 - Quality
* Module 4 – Safety (Nonclinical)
* Module 5 – Efficacy (Clinical)
 Module 1

Module 1 contains the administrative and

prescribing information documents specific to each
regional regulatory agency.

application form,
application fees
Need to do the study
labelling and package leaflet details
Summary of product characteristics (SPC)
Foreign clinical data
 Module 2

2.1 Table of Contents

2.2 Introduction
2.3 Quality overall summary
2.4 Nonclinical overview
2.5 Clinical overview
2.6 Nonclinical written summaries
2.7 Clinical summary.

A one-page introduction of the pharmaceutical

description should be provided

Comment on GMP
 2.3 Quality overall summary
an overview of Module 3
emphasize the critical key parameters of the
product
provide justification in cases where guidelines
are not followed.
discussion of key issues that integrate
information from other modules (e.g.
qualification of impurities via toxicological
studies) with cross reference to the other
modules in CTD
Max pages: 40; The summary may be longer for biotechnology
products and should not exceed 80 pages (excluding tables and
figures).
 2.4 Non-clinical overview
Comprehensive factual synopsis of the non-clinical data
with interpretation of the data,
the clinical relevance of the findings
cross-linking with the quality aspects of the
pharmaceutical and the implications of the nonclinical
findings for the safe use of the product (i.e. as applicable
to the labelling).

Integrated and critical assessment of

*pharmacological
*pharmacokinetic
*toxicological information

Max pages: 30
A comment on the GLP status of the studies
 2.5 clinical overview
A high-level summary and analysis of the clinical data in
the CTD.
critical assessment of the clinical development and
clinical efficacy with regard to the safety data, supporting
the SPC and the benefit/risk assessment.
Assess the quality of the design and performance of all
the studies and include a statement regarding GCP
compliance.
a brief overview of the clinical findings including
important limitations e.g. lack of comparisons with an especially
relevant active comparator, absence of information on some patient
populations.
evaluation of benefits and risks based on the conclusions
of the relevant clinical studies.
Max pages: 30
 2.6 Non-clinical summary
Document as written (text) and tabulated summaries
a summary of the pharmacological, pharmacokinetic
and toxicology studies performed ordered by in vitro,
in vivo, species, route and then duration
age and gender related effects (if applicable)
Integrated information - across studies and across
species
exposure in the test animals should be related to
exposure in humans given the maximum tolerated
dose.
Max pages : 100 -150
 2.7 clinical summary
Document as written (text) and tabulated
summaries
detailed, factual summarization of the clinical
information in Module 5 and any post marketing
data for products that have been marketed in
other regions.
The comparison and analyses of results across
studies should focus on factual observations
Pages : 50 – 400 (excluding tables).
 Module 3
Chemical-pharmaceutical and biological
information for both chemically active
substances and biological medicinal
products.
Table of contents to direct the reviewer
around the document
Body of text on information

Adherence to the principle of GMP

All analytical test procedures must be described in
sufficient detail for reproducibility
All procedures need to be validated and the results of the
validation studies must be provided.
 Module 3 sections :SPARC
Section S - drug substance
• Section P - drug product
• Section A - appendices which includes
information referenced in the core dossier and
adventitious agents safety evaluation i.e.
transmissible spongiform encephalopathy
agents.
• Section R - any regional information
e.g. executed batch records (USA only) and the process
validation scheme for the drug product (EU only).
• Section C - key literature references, if
applicable.
 Module 4
nonclinical study reports
ToC
Detailed reports of each study
appendices containing information
referenced in the module
key references
 Module 5
clinical study reports
ToC
Detailed reports of each study
appendices containing information
referenced in the module
key references
 Electronic Common Technical
Document (eCTD)
ICH Multidisciplinary 2 Expert Working Group
(M2 EWG)

In May 2001, step 2 of the eCTD process

was agreed by ICH
 eCTD
Role of the eCTD: to provide the ability to
transfer the CTD from industry to a
regulatory authority.

The eCTD is an XML (Extensible Markup

Language) catalogue with links to the
actual files in the CTD submission.
The elements defined in the specification of
the "Step 2 eCTD for testing"
1. XML based backbone
- defines the overall structure of the submission.
2. Directory Structure
- defines the physical folder of the files and follows the
hierarchy of CTD.
3. File formats
- Portable Document Format (PDF) and XML.
- JPEG, PNG or GIF may be used for higher resolution
eCTD: XML based backbone
- defines the overall structure
- manages the metadata for the entire
submission and for each document within the
submission.
- provides the logical structure for the entire
eCTD
- allows the eCTD submission to be viewed via a
web browser and can be loaded on a Web
server.

(Metadata is descriptive data about the submission or

file)
 ANNEX : Granularity Document
Ganularity of the paper and electronic
submissions should be equivalent
 Document as per CTD
Document – paper submission

File -----------Electronic submission

 Display of information
Scientific aspects
Text format
Margins
Paper size
Numbering of pages
Acronyms & Abbreviations in each modules
References
 Display of information
Clarity in scientific information
No ambiguity
Transparency
Flow of information in order
- to facilitate the review of the basic data
- to help a reviewer become quickly oriented to the application contents
margins that allow the document to be printed on both A4
paper (E.U. and Japan) and 8.5 x 11” paper (U.S.)
Left hand margin – gutter for binding
Font: Times New Roman, 12-point for narrative text.
Reference citation - in accordance with the current edition
of the Uniform Requirements for Manuscripts Submitted
to Biomedical Journals, International Committee of
Medical Journal Editors (ICMJE)