CTD and eCTD

CTD and eCTD

Sri Harsha Gonnuru

Student of online Professional degree in pharmaceutical regulatory affairs (PDPRA), James Lind
Institute, India

The objective of this paper is to outline CTD, eCTD and their various modules

CTD and eCTD:

To increase international harmonisation of technical requirements to ensure that safe, effective,

and high-quality medicines are developed and registered there is a joint initiative involving both
regulators and research‐based industry representatives of the European Union, Japan and the
USA in scientific and technical discussions of the testing procedures1. The purpose of Common
technical document (CTD)is to provide a harmonized structure and format for new drug
applications. The CTD was agreed upon in November 2000 in San Diego USA and the use of
CTD is mandatory as from July 2003 in European Union and Japan. The CTD is not intended to
indicate what studies are required but the focus of the CTD is to provide a common format for
the preparation of a well-structured submission according to the modular framework described in
the ICH guidelines3. The interface and international specification for the pharmaceutical industry
to agency transfer of regulatory information is electronic common technical document (eCTD).
This is based on the Common Technical Document (CTD) format and was developed by the
International Council for Harmonisation (ICH) Multidisciplinary Group 2 Expert Working
Group3. ICH‐eCTD is an internationally driven standard designed to reduce cost in the
administration, assessment and archiving of applications for marketing authorization of
medicinal products for human use, to reduce the use of paper and streamline the assessment
process making the system more efficient.

On May 5, 2015, the U.S. Food & Drug Administration published a final, binding guidance
document requiring certain submissions in electronic (eCTD) format within 24 months. The
projected date for mandatory electronic submissions is May 5, 2017 for New Drug Applications
(NDAs), Biologic License Applications (BLAs), Abbreviated New Drug Applications (ANDAs)
and Drug Master Files (DMFs)4.

The E.U. and its European Medicines Agency began accepting eCTD submissions in
2003.However, in February 2015, the "EMA announced it would no longer accept paper
application forms for products applying to the centralized procedure beginning 1 July 2015."The
EMA verified on that date that it would no longer accept "human and veterinary centralized
procedure applications" and that all electronic application forms would have to be eCTD by
January 20165.
 CTD and eCTD

Common Technical Document (CTD):

The CTD is categorized into 5 modules as given below6.

 Module 1: Regional Administrative Information.

 Module 2: Introduction, Quality Overall Summary, Nonclinical overview, Clinical
overview, nonclinical written and tabulated summaries, clinical summary
 Module 3: Quality
 Module 4: Nonclinical Study Reports
 Module 5: Clinical Study Reports

The CTD triangle is as shown below6

 CTD and eCTD

Module 1: Regional Administrative Information

Module 1 of the CTD describes the administrative information and prescribing information (for
example, the application form, the proposed product information and labelling). Module 1 is not
strictly included in the CTD since it contains documents that are specific to each region, e.g.
application forms or the proposed label7.

Module 2: Introduction, Quality Overall Summary, Nonclinical overview, Clinical

overview, nonclinical written and tabulated summaries, clinical summary

There are seven sections in Module 2 that should be maintained in the following order8:
 2.1 Table of contents
 2.2 Introduction
 2.3 Quality Overall Summary
 2.4 Non-clinical Overview
 2.5 Clinical Overview
 2.6 Non-clinical Written and Tabulated Summaries
 2.7 Clinical Summary

Module 3: Quality

Chemistry, Manufacturing, and Controls reports for the product are included in Module 3 of the
registration dossier. Sections on both drug substance and drug product are included in this
module. The main headings in this section (that must not be altered) are as follows:
 3.1 Table of contents of Module 3
 3.2 Body of data
 3.2.S Drug Substance
 3.2. P+ Drug Product
 3.3 Literature references used in Module 3

Module 4: Non-clinical study reports

Non-clinical reports included in Module 4 of the dossier. The main headings in this section (that
must not be altered) are as follows8:
 4.1 Table of contents of Module 4
 4.2 Study reports
 4.2.1 Pharmacology
 4.2.2 Pharmacokinetics
 4.2.3 Toxicology
 4.3 Literature references used in Module 4
 CTD and eCTD

Module 5: Clinical study reports

Clinical reports included in Module 5 of the dossier. The main headings in this section (that
must not be altered) are as follows8:
 5.1 Table of contents of Module 5
 5.2 Tabular listing of all clinical studies
 5.3 Clinical study reports
 5.3.1 Reports of biopharmaceutic studies
 5.3.2 Reports of studies pertinent to pharmacokinetics using human biomaterials
 5.3.3 Reports of human pharmacokinetic (PK) studies
 5.3.4 Reports of human pharmacodynamic (PD) studies
 5.3.5 Reports of efficacy and safety studies
 5.3.6 Reports of post-marketing experience
 5.3.7 Case report forms and individual patient listings
 5.4 Literature references.


Electronic Common technical Document (eCTD):

The eCTD has five modules as given below:

1. Administrative information and prescribing information

2. Common technical document summaries
3. Quality
4. Nonclinical study reports
5. Clinical study reports

Data Structure of eCTD9:

The eCTD is a message specification for the transfer of files and metadata from a submitter to a
receiver. The primary technical components are:

 A high-level folder structure (required)

 An XML "backbone" file that provides metadata about content files and lifecycle
instructions for the receiving system
 An optional lower level folder structure (recommended folder names are provided in
Appendix 4 of the eCTD specification)
 Associated document type definitions (DTDs) and stylesheets.

For quick referencing of information, the XML backbone allows agencies to automatically
upload the sequence into their systems and hyper-linking. Since all files are submitted
electronically there is no need for agencies to scan documents or industry to print, transport and
 CTD and eCTD

store masses of paper. Changes and updates to the dossier are easy for reviewers to identify, and,
with electronic submission portals, can be presented to the authorities within minutes of
completion, drastically reducing processing time10.

References:

1. "Guidance for Industry, ICH M4: Organization of the CTD" 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
2. CTD AND ECTD. (n.d.). Retrieved from
http://www.authorstream.com/Presentation/manohar.kasturi-1570061-ctd-ectd/
3. Common Technical Document. (2019, August 14). Retrieved from
https://en.wikipedia.org/wiki/Common_Technical_Document
4. Guidance for Industry: Providing Regulatory Submissions in Electronic Format—Human
Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications.
(2006). Biotechnology Law Report, 25(1), 35-45. doi:10.1089/blr.2006.25.35
5. “Electronic Application Forms Mandatory for EU Centralized Procedure.” Regulatory Affairs
Professionals Society (RAPS), www.raps.org/regulatory-focus%E2%84%A2/news-
articles/2015/7/electronic-application-forms-mandatory-for-eu-centralized-procedure.
6. “CTD.” ICH, www.ich.org/products/ctd.html.
7. Jordan, Debbie. “An Overview of the Common Technical Document (CTD) Regulatory
Dossier.” Medical Writing, vol. 23, no. 2, 2014, pp. 101–105.,
doi:10.1179/2047480614z.000000000207.
8. Australian Government Department of Health. “CTD Module 1.” Therapeutic Goods
Administration (TGA), Australian Government Department of Health, 10 July 2019,
www.tga.gov.au/ctd-module-1.
9. “Electronic Common Technical Document.” Wikipedia, Wikimedia Foundation, 7 Jan. 2019,
en.wikipedia.org/wiki/Electronic_common_technical_document.
10. “What Is Regulatory Affairs?” Trac Services, www.tracservices.co.uk/what-is-regulatory-
affairs/.