This document provides an overview of the electronic Common Technical Document (eCTD) format used for regulatory drug submissions. It discusses the history and goals of the ICH and eCTD, the components and structure of an eCTD, best practices for preparing documents, and software options. Key points covered include the folder structure, use of XML and metadata, concept of reuse and granularity, and comparing the benefits of eCTD to traditional paper submissions. The conclusion emphasizes that adopting eCTD is essential to joining the electronic bandwagon, while also needing intermediate steps to fully transition from paper CTD formats.

1. Presented by Md. Zakaria Faruki
Asst. Manager, Quality Assurance
OPL
Training on
Electronic Common Technical
Document (eCTD)

2. The ICH
 The International Conference on Harmonisation (ICH) was formed in
April 1990 hosted by EFPIA (European Federation of Pharmaceutical
Industries and Associations) in Brussels as a joint regulatory
consortium to bring together the technical requirements of respective
regulatory agencies and standardize the common portions of drug
applications.
Observers
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3. Common Technical Document (CTD)
Representatives of the regulatory agencies and industry
associations of EU, Japan and the US.
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4. eSubmissions History
 Began in late 80’s but insufficient IT capabilities
 1995 – FDA used PDF files with hyperlinks
 1997 – CTD topic of ICH4
 2001 – first eCTD guideline
 2003 – CTD mandatory in EU and first eCTDs submitted
 2006 – lifecycle management a challenge
 In 2007,eCTDs represented 10% of total submissions to CDER.
 2008 – only electronic submissions accepted (either eCTD or non-eCTD)
 2009 – strongly recommend only eCTD format electronic submissions to be
accepted. Paper and other electronic formats to be exception in the EMEA
 It is expected that by the end of 2012, eCTD submissions may represent 40 or 50%
of total submissions to CDER (Center for Drug Evaluation and Research).
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5. What does eCTD consist of?
 Folder or tree structure
 XML backbone file is Table of Contents
 Additional information (Document type definition – rule book
for tags and attributes)
 Regional information and files
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6. Folder Structure
Sections with specific
information in folder names
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7. Preparing documents
Templates should be used where possible
Documents to be:
 technically correct
 have the right granularity
 conform to external regulations/guidelines
 consistent with internal standards and styles – naming
conventions, etc.
 ‘intelligent’ PDF files
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8. Concept of Reuse
 Submit a document once, never submit again.
Concept of Granularity
 Authoring in smaller pieces (granules), allows for greater
flexibility and reuse in the context of submissions.
 If documents are formatted according to ICH granularity and
content needs to change, only those documents that contain new
content will need to be replaced (or appended) and submitted
not the entire section or study report.
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9. What is XML?
 Extensible Markup Language (XML) is an electronic
document and data exchange standard.
XML vs. HTML?
 XML describes and focuses on data. It is information
wrapped in tags that requires another piece of software to
send, receive or display it. The tags are not predefined. XML
is a complement to HTML.
 HTML displays data and focuses on the appearance of data.
Tags are predefined.
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10. DTD
 The purpose of the DTD is to define the building blocks that
can be used in an XML document. It defines the names to be
used for the different types of elements, as well as where they
may occur and how they all fit together.
XSL
 Style sheets, or Extensible Style Sheet Language (XSL),
are files that define the look of the content, including font sizes,
colors, margins, etc.
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11. Metadata
Regional Information
Company Name
Application Number
Date of Submission
Product Name and Type
Application Type
Submission Type
ICH Information
Product, Dosage Form,
Manufacturer, Excipient
Substance & Manufacturer
Indication
Novel Excipient
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12. 012345
util
style
ich-ectd-3-2.dtd
dtd
0000
M1
M2
M3
M4
M5
ich-stf.dtd
us-regional-v2-01.dtd
ectd-1-0.xsl
ich-stf-stylesheet.xsl
us-regional.xsl
index.xml
index-md5.txt
eCTD Folder
Structure
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13. M1M1 M1
M2
M3
M4
M5
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14. Each Section/Tab represents a PDF File
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15. X
M
L
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16. OPL

17. OPL

18. eCTD Software Vendors
1) Extedo / IABG Life Sciences-:
eCTDmanager is an off-the-shelf submission management system of highest quality
and functionality. It provides the eCTD functions of building, viewing, validating and
publishing (electronic and paper) and enables the easy-to-use compilation of
compliant electronic dossiers based on CTD, eCTD and other dossier structures.
2) eCTD Xpress:
eCTD XPress is ISI’s latest web-based solution for creating, managing eCTD lifecycles,
and reviewing eCTD submissions. The application satisfies both regulatory agencies’
and industry sponsors’ requirements for reviewing, compiling, publishing and
archiving of multi-region eCTD submissions. eCTDXPress allows users to separate
technology from content, which improves productivity and time-to-market.
3) Submission Accelerator for eCTD:
It is a complimentary module for CoreDossier® -- automates the assembly and
publishing of compliant eCTD dossiers, including the XML backbones for regional
content.
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19. 012345
0000
M1
M2
M3
M4
M5
util
index.xml
Index-md5.txt OPL

20. 0000
0001
0002
012345
M1
M2
M4
util
0003
0004
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21. Granularity
 Defines how the completed document is broken down,
tagged and stored for reuse
 Determines smallest piece of information that is reusable
 Changing granularity during lifecycle is difficult, therefore
must be planned at the beginning.
 FDA Guidance
Each document should be provided as a separate file
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22. ‘intelligent’ PDF files
 A file converted to special PDF format enabling links and
bookmarks to be applied, and hence is searchable.
Cross referencing documents
 Intradocument links – bookmarks
Most intradocument links can be automatically set using
templates
To set each link manually would take MANY hours
 Interdocument links
Cross reference documents in context of other documents.
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23. Cross referencing submissions
 Inter submission links
Cross references of submissions in context of other
submissions, e.g. variations.
Time frames
 Once all documents are written, checked and formatted
setting bookmarks and links take from 2 to 12 weeks.
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24. Eye openers
 Global application
 Life cycle history easily accessible
 Ease of compilation and review once system is up and running
 Intersubmission checks made possible by both applicant and
reviewer
 Authenticity of documentation easy to verify.
bombshell
 Extensive software programme needed to support the system
 Software programme used in EU costs €20,000 per USER
 Extensive IT support needed by applicant and regulator.
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25. Comparing paper CTD and eCTD
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26. Conclusion
 Great idea but need intermediate steps to get there
CTD format to be adopted immediately
NeeS in interim
 Essential to join electronic bandwagon
 To explore the stages of developing an eCTD strategy and
approach.
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27. Strategy & Approach
Save a Tree!!
• NCE is approx 240,000 pages, Paper for this would be 672 kg, Equivalent to ONE
average tree.
•An entire tree is required to submit a single copy of the application form one
applicant to one health authority
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28. OPL