The document discusses the key changes and objectives of ICH eCTD 4.0. Major changes include bi-directional communication between applicants and agencies, assigning each document a unique UUID number, consolidating multiple files into a single XML file, replacing the operation attribute with options for replacing or appending documents, and allowing metadata to be edited after submission. The objectives are to improve processing and review between applicants and agencies and make submissions and publishing more effective. Adoption of ICH eCTD 4.0 will require system upgrades and additional archival space.

1. ICH eCTD 4.0
Regulatory Affairs
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Topic Content
Objective
Major Changes
Bi-Directional Communication
UUID
XML
Operation Attribute
Metadata
Impact
Best Practices

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What is ICH ?
 The International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation (ICH)
was created in 1990. It’s was joint initiatives both regulators and research-based industry of the EU, US and Japan to
harmonize the registration of Pharmaceutical drug products along with ensuring the safety, efficacy and quality of
medicines.
 In July 2003, ICH Introduce CTD which organised into five modules. Module 1 is region specific and Modules 2, 3, 4
and 5 are intended to be common for all regions and developed by the M4 EWG (Expert Working Group).
 First ICH eCTD Specification 3.2.2 published by M4 EWG in July 2008.
 ICH formed M8 EWG to assume responsibility of all next major version of eCTD in November 2010.
 M8 EWG released first draft version of ICH eCTD 4.0 in December 2015. Since Dec 2015 ICH released many version
of eCTD 4.0 in draft phase for getting response from Agency/Industry to finalized. Final guideline is expected by Q4
2020.

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What is ICH ?

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Objectives
To improve the facilities of processing and review submission between Sponsor/Applicant and
Agency.
To make submission review process more streamline and compatible.
To make publishing more effective and reliable.

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Major Changes
Bi-Directional Communication:-
There will be bi-directional communication between Applicant/Sponsor and Agency.
Sequence 0001 Review Phase
Applicant/Sponsor
USFDA
Any Query or
Comments
Yes
Sequence 0001

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Major Changes
UUID (Universal Unique identifier) no.:-
Every document will be having own UUID (Universal Unique identifier) no.
Document 1
Document 2
Document 2
Document 2
0011
0012
0013
0014
UUID number

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Major Changes
XML file:-
New XML schema designed to improve robustness, flexibility and long term stability of the message.
There will be only single xml file.
ICH eCTD 3.2.2
ICH eCTD 4.0
1. Regional.xml
2. Index.xml
1. xyz.xml

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Major Changes
Operation Attribute:-
We will not see anymore Append operation attribute in ICH eCTD 4.0
We will be able to replace a single file one or more time in the entire life cycle of specific application.
ICH eCTD 3.2.2 ICH eCTD 4.0
1. New
2. Append
4. Delete
3. Replace
1. New
3. Delete
2. Replace

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Major Changes
Operation Attribute:- Replace and Append
Example:
Initially, In (Seq. 0001) we have submitted Stability Data with 6 Months. Now
in seq. 0010 we have to submit stability data with 36 months.
If current document have 6 months stability data with 36 months, then we will
use REPLACE operation attribute otherwise APPEND

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Major Changes
Metadata:-
We will be able to edit the ICH metadata (e.g. manufacturer name, product name, drug substance name etc.)
even after submission locked and submitted to Agency.
Module 2
Module 3

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Impact
A major upgrade on existing system will be require.
Received files and sequence will need to be stored and made available for future reference purpose.
Archival space would require to be increase.
Additional activity need to be done on EDMS (Electronic Document Management System).

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Best Practices
1. For any Administrative Changes we must use Product Correspondence as Submission Type instead of Other in
Column 21 of FDA Form 356h.
2. Please check Paper size in word format prior finalized the document as it should be in Letter (8.5x11) instead of A4.
3. Please ensure following points checked during scanning the documents;
I. 600 DPI (Dot per inch)
II. Paper Size: Letter
III. Portrait and Landscape mode
IV. Format is PDF instead of PDF A
4. Please ensure Zoom Level is 100% in PDF prior starting review of submissions.
How to check and set Zoom Level
I. Press Ctrl+K
II. Go to Page Display
III. Set Zoom
IV. Press Ok

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