After 10 years of eCTD the standard is fit for rejuvenation. Although eCTD has brought many benefits there is still significant room for improvement. This presentation covers different areas: continuous challenges associated with eCTD, Regulatory guidelines and eCTD viewing

1. A decade of eCTD: time to
rejuvenate!
Michiel Stam
Manager Regulatory Operations
Qdossier B.V.

2. Agenda
Introduction
Continuous challenges
Regulatory guidance and specifications
eCTD viewing
eCTD: a rigid structure
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3. Introduction

4. Rejuvenation
“the hypothetical reversal of the aging
process.”
Change directions,
we can improve!
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5. The Aging process
First European eCTD: 24th
January 2003
eCTD v3.0
EU v0.9
Mandated by EMA (1st January
2010)
Ability to accept e-only (January
2010)
EMA Gateway (2012)
(mandatory 1st March 2014
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6. Version history
ICH eCTD specifications
v3.0 (October 2003)
v3.1 (November 2003)
v3.2 (February 2004)
v3.2.1 (June 2008)
v3.2.2 (July 2008)
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EU m1 eCTD
specifications
v0.9 (November 2002)
v1.0 (July 2004)
v1.1 (December 2005)
v1.2 (May 2006)
v1.2.1 (October 2006)
v1.3 (May 2008)
v1.4 (August 2009)
v1.4.1 (November 2011)
v2.0 (September 2013)
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7. The benefits of e-only submissions
Aspect
Paper
eCTD
Transport
--
+ / ++
Handling/ Review
-
++
Life cycle management
--
+
Archival
--
++
Costs
--
+
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8. Continuous Challenges

9. XML Backbone
Use the XML
backbone!
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Huh?? Bone?
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10. eCTD viewer vs. Tracking approval
Baseline of the
current EU dossier
please!
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Latest submitted or
current approved?
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11. Current in eCTD vs. Current Approved
Source: IRISS Life Cycle Group 2009
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12. Document Lifecycle status
Life cycle operation: “New”
Life cycle status: “Current”
Approval status: “Under review”
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13. Regulatory Guidance and
specifications

14. FDA –Providing Regulatory Submissions in
Electronic Format (draft)
“Although some eCTD tools generate leaf titles
that are similar to file names, the two are not
related.”
All modules of the eCTD should contain
descriptive eCTD leaf titles that are:
Short
Meaningful
Indicative of each document's content
Not including the eCTD section number
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15. Leaf titles vs. File names
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16. Swiss Medic - Providing Regulatory
Information in eCTD Format version
Hyperlinks are encouraged to facilitate
navigation > should not be overused
Only if necessary and of real added value.
Important eCTD titles are consistent with cross
references within other documents (e.g. summary
document)
Hyperlinks needed if title in eCTD ToC and
reference in a summary document do not match
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17. Validation
To assure that what has been submitted is fit for
review by the validating agency
Technical: Can technically be processed by agencies?
Business: All data is available to examine the quality,
safety and efficacy of the drug
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18. Technical validation > …. < Business
validation
Consistency in attribute values
across sequences
attributes, file names and folder names within a
sequence
Country codes
Language codes
PI Doc types
Proper reference to “Related Sequence”
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19. Additional “common sense” checks
Cover letter and Application form data is reflected
correctly in the envelope
Use of meaningful titles; e.g.
Proof of Payment vs. Annex 5.2
Note to Reviewer vs. Annex 3
Stability Data Long Term Stability 24 M vs. Stability Data 1
Use of meaningful file names; e.g.
de-form-proofpayment.pdf
vs.
de-form-5.pdf
es-cover-notereviewer.pdf
vs.
es-cover-3.pdf
stability-data-longterm24m.pdf
vs.
stability-data-1.pdf
analytical-procedure-identityelisa.pdf
validation-analytical-procedure-identityhplc.pdf
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20. Conflicting guidelines
eCTD: “do not resubmit the same
document”
CTD (Renewals): “include a copy of the
latest specifications”
eCTD: leave empty
CTD: placeholders “N/A”
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21. Controlled vocabulary
“Regulatory activity”
HL7: “the provision of information about a regulated
product(s) requiring a scientific or regulatory outcome. An
activity may include one or many exchanges (examples of
exchanges may be eCTD sequences, RPS submission
units, etc.)”.
CESP:
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22. Controlled vocabulary
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23. Controlled vocabulary (Cont’d)
“Working documents means draft versions of
summary of product characteristics, package
leaflet, and labeling editable by the Danish Health
and Medicines Authority”
QOS and (non-)Clinical overview?
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24. Errors in guidance
<sequence number>-working documents
„sequence number - workingdocuments’ (no
hyphen)
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25. eCTD viewing

26. eCTD viewing beyond specifications..
Source: IRISS Life Cycle Group 2009
Source: IRISS Life Cycle Group 2009
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27. From multiple to single section
Source: IRISS Life Cycle Group 2009
Source: IRISS Life Cycle Group 2009
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28. Shared documents across sections
Source: IRISS Life Cycle Group 2009
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29. Viewing across products and countries
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30. eCTD: a rigid structure

31. Administrative information
Regional administrative information = country specific
information
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32. Administrative information
Risk management plan:
1.3.8.2 Risk management plan
1.6.2 Risk management plan
1.8.2 Risk management plan
1.13 Risk management plan
1.16 Risk management plan
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(CA)
(GCC)
(EU+CH)
(ZA)
(US)

33. eCTD today
Envelope information + other metadata
GMO
Non-GMO
Orphan
PSMF
RMP
GMO
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RMP
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RtQ

34. eCTD yesterday
Envelope information + other metadata
<cc> SmPC
Agency codes
EMEA = EMA
DKMA = DHMA
USKVBL
AEMPS = ES-AEMPS
Country codes
AT - Austria
BE - Belgium
CZ - Czech Rep.
DE - Germany
DK - Denmark
SmPC ES - Spain
FI - Finland
HR - Croatia
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35. eCTD day before yesterday
Envelope information + other metadata
GMO
Non-GMO
Orphan
DSUR
PSMF
RMP
GMO
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RMP
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RtQ

36. XEVMPD/IDMP principles
XSD schema defining structure
CV
Substance
List of
allowed
substance
names
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CV
Substance
Metadata
List of
allowed ATC
codes
ISO 3166-1
List of
country
codes
Regional
Implementation
guideline
Validation
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37. eCTD tomorrow?
RMP
Controlled
CV List of
Vocabulary
allowed
labels:
List of
allowed
GMO
Non-GMO
labels
(Agency
DSUR
controlled)
RMP
DSUR
v1.0
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38. Allows easy updating of…
Use of the European Agency Acronym
Addition of Other PDF Versions
Addition of Risk Management Plan as a
New Submission Type
Revisions Regarding Agency Names and
Agency Codes
Source: Release notes EU module 1 specification v2.0
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39. Concluding remarks
Continuous education needed
Agency focus moves from technical to non-technical
aspects
(Much) broader/ leaner technical specifications needed
for structure
Well specified implementation guidelines and controlled
vocabulary to assure correct use
Correct application assured by validation tools
(Hopefully with some build in consistency checks)
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40. Thank you !
Michiel Stam
Manager Regulatory Operations
www.qdossier.com