CTD & ECTD format

Present by [Link]
Dadhaniya Hit J 14
Vekariya Yash 15
Department: pharmaceutics
Subject: regulatory affairs

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 Index
 What is a regulatory dossier
 Problem before CTD
 Introducing the CTD
 Origin of CTD
 Significant of CTD
 Structure of CTD pyramid
 Sequence of M4 CTD for registration
 limitation of CTD
 What is eCTD
 Characteristics of eCTD
 Nomenclature for files and eCTD submission
 Benefits of eCTD
 Comparison: CTD vs eCTD
 Summary
 Reference

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  what is regulatory dossier ?

 A regulatory dossier is a comprehensive collection of information about a new

pharmaceutical product. It is submitted to a Health Authority (like CDSCO, FDA,
or EMA) to seek approval for marketed the drug.

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 Problem before CTD
1. Different Formats
Each country had its own submission format and requirements.
No global standard, leading to confusion and frequent formatting errors.

2. Duplication of Work
Companies had to rewrite and reformat dossiers for every region.
Same data had to be presented multiple times in different styles.

3. Slow Review Process

Reviewers struggled with different dossier structures.
Led to delays, misinterpretation, and inefficient reviews.

4. Resource-Intensive
Submissions required huge amounts of paper and time.
High use of manpower and money for preparing and reviewing documents.

5. Delayed Drug Availability

Different requirements caused slow global approvals.
Patients in some countries received new drugs much later.

6. Higher Costs
Multiple dossier versions increased industry costs.
Regulators also spent more time and resources reviewing non-standard documents.
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 Introduction of CTD

The Solution: ICH

 The creation of a single, unified format for regulatory submissions—the
Common Technical Document (CTD).

What is the CTD?

 The Common Technical Document (CTD) is a standardized format for a new drug
application dossier.
 It defines the structure, content, and organization of the information to be
submitted to regulatory agencies.

The Core Principle

 "One Dossier, Multiple Regions."

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 Origine of CTD

The Common Technical Document (CTD) was officially signed off in November 2000
during the 5th ICH Conference held in San Diego, California.
Q S
E M M4: The Common Technical Document (CTD)

It is template for presenting data in the dossier

CTD is Joint Effort of Three Major Regulatory Agencies

1. European Medicines Agency (EMA/EMEA), Europe
2. Food and Drug Administration (FDA), USA
3. Ministry of Health, Labour and Welfare (MHLW), Japan

CTD has since been adopted worldwide, including by regulatory authorities in

Canada, Switzerland, Australia and WHO.
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 Significance of CTD
1
Avoids preparing multiple regional dossiers
2
Common standardized format saves time and resources
3
Simplifies review and approval processes
4
Enables faster availability of new medicines
5
Improves information exchange among regulatory authorities
6
Supports electronic submissions (eCTD)
7
Enhances lifecycle management and product updates
8
Promotes global harmonization

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 Structure of CTD pyramid

The Five Modules

The CTD is organized into a five-module pyramid.

Module 1: Regional Administrative Info

Module 2: CTD Summaries
Module 3: Quality (CMC)
Module 4: Non-Clinical Study Reports
Module 5: Clinical Study Reports
Modules 2-5 are common across all regions. Only
Module 1 is region-specific.

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 Modul 1: regional administrative information

Contains region-specific documents. (e.g., Form 44 for India, FDA Form 356h for
USA).

Includes:
 Application forms and cover letters
 Product labelling and packaging information
 Patent details, fees, and legal documents
 Information required by the local authority (e.g., FDA Form 356h, EMA
application form).
Note: Module 1 according to the region.

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  Modul 2: CTD summary

2.2 Introduction 2.3 Overall Quality Summary (OQS)

2.1 Table of Contents
Drug name, Dosage form, Route Drug substance summary, Drug product
Provides a complete list
of administration, summary, Manufacturing process
of all sections included in
Pharmacological category, overview, Quality controls and
Module 2.
Proposed clinical use specifications, Stability summary

2.4 Non-Clinical Overview 2.5 Clinical Overview

Pharmacology studies, Clinical pharmacology,
Pharmacokinetics (ADME), Clinical efficacy, Clinical
Toxicology studies safety

2.6 Non-Clinical Written and Tabulated 2.7 Clinical Summary

Summaries Clinical pharmacology, Clinical
Written summaries (pharmacology, efficacy, Clinical safety, Study
pharmacokinetics, toxicology), reports summarized in structured
Tabulated summaries (tables of all format
study data)
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  Modul 3: quality (CMC)

3.1 Module 3 – Table of Contents

Complete list of all subsections within Module 3.

3.2 Body of Data (Quality Information)

3.2.S – Drug Substance 3.2.P – Drug Product

• General information about the API • Description and composition of the finished dosage form
• Manufacture details • Pharmaceutical development
• Characterization • Manufacturing process and process controls
• Quality control tests and specifications • Excipients information
• Reference standards • Control of drug product (specifications, methods)
• Container–closure system • Packaging information
• Stability data • Stability data

3.3 Literature References

Published scientific literature cited in Module 3.
Includes research papers, pharmacopeial references, monographs, and supporting data.

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 Module 4: non-clinical study report

4.1 Module 4 – Table of Contents

Complete index of all nonclinical study reports included in this module.

4.2 Nonclinical Study Reports

4.2.1 Pharmacology 4.2.2 Pharmacokinetics (ADME) 4.2.3 Toxicology

Primary pharmacodynamics Absorption Single-dose toxicity
Secondary pharmacodynamics Distribution Repeat-dose toxicity
Safety pharmacology Metabolism Genotoxicity
Pharmacodynamic drug interactions Excretion Carcinogenicity
Toxicokinetic studies Reproductive and developmental
Drug interaction studies toxicity
4.3 Literature References Local tolerance
Scientific literature and publications supporting the nonclinical data.

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 Module 5: Clinical study report
5.1 Module 5 – Table of Contents
Complete index of all clinical study reports included in this module.

5.2 Tabular List of All Clinical Studies

Study titles
Study types
Study codes
Study populations

5.3 Clinical Study Reports

5.3.1 Biopharmaceutical Study Reports
5.3.2 Human Biomaterials & Pharmacokinetic Studies
5.3.3 Human Pharmacokinetic (PK) Study Reports
5.3.4 Human Pharmacodynamic (PD) Study Reports
5.3.5 Efficacy and Safety Study Reports
5.3.6 Post-Marketing Experience Reports
5.3.7 Individual Patient Listings & Case Report Forms (CRFs)

5.4 Literature References

Scientific publications supporting clinical findings
Research articles, reviews, and previously published clinical evidence

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 Sequence of M4 CTD for registration new drug
Module /
Sr. No. ICH Guideline Code Description / Focus Area
Section

Provides the overall structure and organization

1 M4 General CTD guideline
of the CTD (modules, format, headings, etc.)

Covers Quality information — Chemistry,

2 M4Q Quality Manufacturing, and Controls (CMC) for drug
substance and product.
Covers Nonclinical / Preclinical studies —
3 M4S Safety pharmacology, pharmacokinetics, and
toxicology data.
Covers Clinical studies — human
4 M4E Efficacy pharmacokinetics, pharmacodynamics, clinical
efficacy, and safety.

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 Limitation of CTD

 Originally designed for paper-based submissions, requiring large volumes.

 Difficult to update or modify after submission.
 Requires physical logistics for submission and archiving.
 Time-consuming for both applicant and regulator.
 Environmental concerns due to heavy paper usage.
 Limited flexibility for real-time updates
 Risk of loss or damage to documents
 Difficult to track versions and maintain consistency across multiple copies.
 Increases overall cost of submission due to printing, binding, and shipping.

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 What is eCTD

Electronic Common Technical Document

• Common format for Quality, Safety, and Efficacy information
• The eCTD is the electronic equivalent to the CTD. [CTD=eCTD]
• An interface for industry to agency transfer of regulatory
information

eCTD in simple words:

The eCTD backbone is an XML file representing the structure of the
submission, it includes links to files and other metadata such as
check sum.

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eCTD Changes
• In eCTD, XML replaces the pdf table of contents. It works as an electronic
index that arranges and links all the files.
• Manage meta-data for the entire submission.
• It creates a clear table of content and helps you easily find and open the
correct document.
• Information is divided into smaller parts that it is easier to manage and
follow the ICH eCTD rules.
• Life Cycle Management:
- First you submit the main application.
- Later you can send small updates whenever something changes.
- You only need to resubmit the parts that were updated not the whole
file again
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 Characteristics of eCTD

[Link] Referenced in the XMLBackbone(s)

(Extensible Markup Language)

REASONS:
[Link] manages the large data for the entire submission and for each document within the
submission.
[Link] XML backbone allows the eCTD submission to be viewed via a web browser and
can be loaded on a Web server.

[Link] file formats that can be included in the eCTD are Portable Document Format
[PDF] and Extensible Markup Language XML.
However other formats can be used for graphs and images
JPEG
PNG
GIF
- may be used for higher resolution.
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 Characteristics of eCTD

3. All eCTD Submissions Include Module 1

Module 1 Identifies following important information:

• Company Name
• Drug Name
• Submission Type
• Submission Date
• Application Number
• Sequence Number

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  Nomenclature for files and eCTD submission

EXAMPLE:- MODULE 2 FILE NOMENCLATURE AND eCTD submission

Description File Name

2.2 introduction 22-intro
2.3 Quality overall 23-qos
summary
2.4 Non clinical overview 24-noncling-over
2.5 Clinical overview 25-clin-over
2.6 Non clinical written 26-noncling-sum
and tabulated
summaries
2.7 Clinical summary 27-clin-sum

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 eCTD format of CANADA

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 Screenshot of Complied eCTD

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 Benefits of eCTD

• Improved handling and archiving of submissions

• Better information management support of Life Cycle Management
• Immediate access to complete and up-to-date information
• Search functionality for assessors and increased tracking ability
• Facilitated evaluation and better visibility of the process
• Reduced workload and reuse of information for assessment reports.
• Controlled communication with external experts
• Better use of resources
• Simplified business process
• Better communication with industry
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 Comparison: CTD vs eCTD

Aspects CTD eCTD

Format Paper/static pdf Fully electronic

Navigation Manual Hyperlinked & searchable

Lifecycle Not supported Fully supported

Submission Physical pdf Through electronic

gateways

Validation None Required technical checks

Acceptance Limited Mandatory in major

regions

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 Summary

 CTD is a globally harmonized format created by ICH to standardize drug regulatory submissions.
 Organized into 5 modules, where Modules 2–5 are common for all regions and Module 1 is
region-specific.
 Solves problems of earlier submissions like multiple formats, duplication of work, and long review
timelines.
 ECTD is The electronic version of CTD using an XML backbone for structure, navigation, and
lifecycle management.
 Allows easy updates, version tracking, faster review, and improved data organization.
 Both CTD and eCTD support efficient review, reduce workload, improve global harmonization, and
help bring medicines to market faster.

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 Question

1. What does the Chemistry Manufacturing Control (CMC) section of a regulatory submission
typically include?
2. What is the role of the ICH guidelines in harmonizing regulatory requirements across different
regions ?
3. Write full form of following abbreviations: CTD, ICH, ANVISA
4. Differentiate CTD & ECTD ?
5. Analyze how the regulatory requirements for combination products differ from those for
traditional drug products.

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 Reference

1. Virkar, K. A., Ghige, T., Velhal, A. B., & Redasani, V. (2022).

A Review of the Preparation of Regulatory Dossiers in CTD Format and eCTD Submissions
. International Journal of Pharmaceutical Research and Applications, 7(4), 808–818. [Link]
g/10.35629/7781-0704808818
2. [Link]
3. [Link]
4. [Link]
5. [Link]

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Thank
You !!
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