GlaxoSmithKline Biologicals transitioned from paper dossiers to electronic submissions using eCTDs. They designed processes and systems centered around an electronic document management system to author, publish, and archive regulatory documents and submissions. Lessons learned included focusing on using eCTD to improve existing processes rather than just for compliance, maximizing reusability of documents, and ensuring flexibility and integration across systems.
Informa Life Sciences’ Inaugural Conference on e-Submissions
1. Informa Life Sciences’ Conference on e-Submissions
From paper dossiers to electronic
submissions
Alain Seront
GlaxoSmithKline Biologicals
18-19 October 2011| Zurich, Switzerland
2. GlaxoSmithKline Biologicals
1945 Founded as RIT (Recherche et Industrie Thérapeutiques)
é
1968 Becomes SmithKline RIT
1989 SmithKline merges with Beecham
2000 GlaxoWellcome and SmithKline Beecham merge
GSK Biologicals: the vaccine business of
GlaxoSmithkline
Over 30 marketed vaccines available worldwide
11.000 employees worldwide / 7000 in the
p y
Headquarter in Belgium
3. GlaxoSmithKline Biologicals
Manager of the Document Management and
Publishing Team at GlaxoSmithKline Biologicals
10 years in Pharma
Regulatory operations
R l t ti
Publishing
e submissions
e-submissions (project management)
alain.seront@gskbio.com
alain seront@gskbio com
4. Topics
Background
Design of the processes and systems for eCTD
Overall process
Content Plan
Structure of the electronic document management system (eDMS)
Authoring process
Publishing Process
Viewing and archiving eCTDs
Positive and negative lessons learned
eCTD implementation strategy
Reusability of documents and submissions
Flexibility
Systems integration
6. Background
GlaxoSmithKline
GlaxoSmithKline Pharma GlaxoSmithKline Biologicals
Early adopter of the eCTD Late adopter of the eCTD
7. Background
Start eCTD
EMEA implementing
l mandatory for
d f
announced new eCTD / e-submissions
eCTD NeeS / paper First eCTD in EU – CP 17 products and
mandatory for publishing, QC sequence send >600
e-submission
b i i and archiving to
t EMEA by GSK
b sequences iin
tools at GSK Bio First
for Jan. 2010 Bio worksharing in eCTD
eCTD submitted
by GSK BIO
December February November January October
2008 2009 2009 2010 2011
9. It’s not only eCTD (and NeeS)!
From paper dossiers to electronic
submissions?
b i i ?
or
From paper dossier to electronic
submissions AND paper submission?
Paper submissions are still part of the
game!
10. Overall process
Regulatory Clinical NonClinical Technical Clinical
Affairs / Ops Regulatory Regulatory
Initiate C t t
I iti t Content
Plan
Setup folder
structures in eDMS
Authoring in eDMS (communities)
Link from eDMS communities to eDMS dossier area
Create eCTD seq. in
publishing tool
Populate eCTD seq.
with docs from
eDMS (following
content plan)
Publish
QC (validators + manual QC following content plan)
Submit to
authorities
Archive
11. Overall process
Regulatory Clinical NonClinical Technical Clinical
Affairs / Ops Regulatory Regulatory
Initiate C t t
I iti t Content
Plan
Setup folder
structures in eDMS
Authoring in eDMS (communities)
Link from eDMS communities to eDMS dossier area
Create eCTD seq. in
publishing tool
Populate eCTD seq.
with docs from
eDMS (following
content plan)
Publish
QC (validators + manual QC following content plan)
Submit to
authorities
Archive
12. Content plan
Excel spreadsheet with macros
Purpose
List ll d
Li t all documents that go in a dossier
t th t i d i
with their location in the CTD
And their order in a specific section
Information on lifecycle for each document
Documents linked in more than 1 leaf
13. Content plan
Purpose
Help authors to define names for documents
and comply with naming conventions
For leaf titles
For PDF file names
Define documents granularity for each product
Quality check for dossier managers /
publishers
14. Content plan
Several content plans
Generic content plan
Product specific content plan
Submission specific content plan
Dossier specific content plan
15. Content plan
Several content plans
Generic content plan
Capture GSK principles for all modules regarding
General principles of document granularity
Naming conventions (leaf title, PDF file name)
Product specific content plan
Capture module 3 principles for a specific
product
Drug substances and drug product presentation
Product specific documents granularity and naming
conventions
16. Content plan
Several content plans
Submission specific content plan
To reflect modules and documents relevant for a
submission type, idependently from a product
E.g. : PSUR submission
g
Dossier specific content plan
To reflect modules and documents relevant to a
specific dossier / submission
17. Overall process
Regulatory Clinical NonClinical Technical Clinical
Affairs / Ops Regulatory Regulatory
Initiate C t t
I iti t Content
Plan
Setup folder
structures in eDMS
Authoring in eDMS (communities)
Link from eDMS communities to eDMS dossier area
Create eCTD seq. in
publishing tool
Populate eCTD seq.
with docs from
eDMS (following
content plan)
Publish
QC (validators + manual QC following content plan)
Submit to
authorities
Archive
18. Structure of the eDMS
Structure of the eDMS
Authoring in eDMS
Communities
Dossier Area
19. Structure of the eDMS
electronic document management system
Templates Communities Dossiers Area
Area Area
Drug Product
Quality
Submission Type
Clinical V# Variation II/18
M1 publishing tools
Registration
Management
M2
Labeling
20. Structure of the eDMS
3 main areas
Templates area
Templates for most of submission documents
Communities area
Contains ll th d
C t i all the documents from the
t f th
communities which contributes to the dossier
writing (Quality CMC, Safety, Labelling, Clinical,
...)
Main storage for “source” documents written for
dossiers
Each community has its own folder structure to
manage it own d
its documentst
21. Structure of the eDMS
3 main areas
Dossiers area
Contains all the dossiers
Organised by product / submission type / dossier
Dossier folder structure: CTD or mirrors the
composition of the submitted dossier
Populated by linking documents from the
p y g
Communities
Source area for the publishers to build the
dossier
d i
“Where used?”: for each document, in which
dossier it has been included
22. Authoring
Process
Take template from templates area
Paste into Community area
Link into dossier area
Start authoring in Community or dossier area
C C docu e ts ot dossier or even product
CMC: documents not doss e o e e p oduct
related authoring in Community area
Dossiers Managers: document related to a
dossier / submission authoring in dossier
area
All documents are authored in eDMS
23. Overall process
Regulatory Clinical NonClinical Technical Clinical
Affairs / Ops Regulatory Regulatory
Initiate C t t
I iti t Content
Plan
Setup folder
structures in eDMS
Authoring in eDMS (communities)
Link from eDMS communities to eDMS dossier area
Create eCTD seq. in
publishing tool
Populate eCTD seq.
with docs from
eDMS (following
content plan)
Publish
QC (validators + manual QC following content plan)
Submit to
authorities
Archive
24. Publishing process
eCTD – NeeS for one product
eCTD – NeeS for several products
Same content of th d i
S t t f the dossier
e.g. Worksharing submission
eCTD – NeeS for several regions
Paper only
eCTD – N S and paper
CTD NeeS d
28. Publishing process
eCTD and paper
import
i t
eDMS
paper
eCTD publishing tool
publishing tool
publish
p blish
compile
0004
m1
m2
m3
util
index.xml
index-md5.txt
29. Overall process
Regulatory Clinical NonClinical Technical Clinical
Affairs / Ops Regulatory Regulatory
Initiate C t t
I iti t Content
Plan
Setup folder
structures in eDMS
Authoring in eDMS (communities)
Link from eDMS communities to eDMS dossier area
Create eCTD seq. in
publishing tool
Populate eCTD seq.
with docs from
eDMS (following
content plan)
Publish
QC (validators + manual QC following content plan)
Submit to
authorities
Archive
31. Viewing and archiving eCTDs
Specific constraints
Current view must be available
Historical view must be available
In-progress sequence (not archived yet) must
be included in viewer
Hyperlinks must be functional
From the xml backbone to documents
Between documents
34. Implementation strategy
Implement a system to comply with
eCTD technical requirements?
Not a lot of return on investment
eCTD
CTD
Focus on implementing all the
possibilities that eCTD brings?
Focus on how to “use” eCTD
use
implementation to refine and improve
Late adoption our processes and tools?
of eCTD
35. Implementation strategy
e eDMS R eDMS
Publishing
g Publishing
g
C Viewing
P Viewing
T Tracking S Tracking
Archiving Archiving
D
36. Implementation strategy
0004 (eCTD)
m1
m2
m3
M util
index.xml
Y index-md5.txt
S
eDMS
Y Viewing paper
S Tracking
T Archiving
E 0000 (NeeS)
M m1
m2
S m3
ctd-toc
m1-toc
m2-toc
m3-toc
RPS
37. Implementation strategy
Implement a system just to comply with
eCTD? eCTD as the eDMS / publishing
systems?
If the standard changes, the systems must
changes
change
eCTD
CTD
Implement eCTD as one output from
the eDMS / publishing systems?
Reusability of the systems for other
outputs
38. Reusability
Of documents, allowed by
Chosen granularity (lot of small granules)
Omit context of use in documents (e g no
(e.g.
reference to brands, region or type of
submission))
Context can be given by
Location of d
L ti f document i eDMS d i area
t in DMS dossier
Location of document in published dossier
39. Reusability
Of dossier
Principles
Start with one assembly (generally eCTD / NeeS)
Import documents from eDMS to publishing tool
(
(most publishing time consuming task)
p g g )
Reuse (clone) the first assembly for
Another product (e.g. Worksharing)
Another region (e.g. from EMA to Switzerland)
Another format (e.g. from eCTD to paper)
Make the most out of the first published
dossier
d i
40. Flexibility
Flexibility
Changes internal to the company
eCTD for new countries (e.g. Switzerland) or new
procedures (e.g. MRP)
Outsourcing of some activities?
Changes from regulatory authorities
Worksharing and grouping (Jan. 2010)
New validation rules for NeeS and eCTD (Sept 2011)
(Sept.
eCTD next major version – RPS (some day)
Current processes and systems must
accommodate these changes
42. Systems integration
Repository A
Document
Reviewing management
(lifecycle)
Planning
Authoring Publish
tracking Repository B
Review
Repository D Archive published
dossier
Repository C
Distribute
(authorities
/ affiliates)
43. Systems integration
Document
Reviewing management
(lifecycle)
Authoring Publish
Review
Archive
A hi published
bli h d
dossier
Distribute
(authorities
( h i i
/ affiliates)
44. Systems integration
Management
Reviewing
(lifecycle)
(lif l )
Planning
Authoring Publish
Review
Archive
A hi published
bli h d
dossier
Distribute
(authorities
( h i i
/ affiliates)
45. Systems integration
Management
Reviewing
(lifecycle)
(lif l )
Authoring Publish
Review
Archive
A hi published
bli h d
dossier
Distribute
(authorities
( h i i
/ affiliates)
tracking
46. Final words
Think what eCTD (or any other new
standard) could bring to your business
t d d) ld b i t b i
and not only what is the minimum you
need to have to comply with eCTD (or
any new standard)
y )
47. Final words
Flexibility… flexibility… flexibility
Reusability… reusability
Reusability reusability… reusability
Integration… integration… integration
51. eDMS and Publishing
For each document in eDMS
Some attributes are mandatory
Automatically used to populate attributes in
publishing tools
Are included in eCTD backbone PDF table of
backbone,
contents (for NeeS and paper)
52. eDMS and Publishing
eDMS Example eCTD NeeS Paper
attributes
Document name 2.3 - V2011000418 - - -
Quality Overall
Summary
eCTD name Quality Overall Leaf title Entry in PDF ToC Entry in ToC
Summary on
change
h Reference i cross-
R f in Reference i cross-
R f in
manufacturing site references to this references to this
document document
Output file name qos-v2011000418 File name File name -
(qos-v2011000418.pdf) (qos-v2011000418.pdf)
53. eDMS and Publishing
Those attributes in eDMS
Ensure efficiency
Attributes introduced and checked once
Reuse each time the document is used in a
dossier
Ensure quality
Content of the attributes are defined by the
content plan
Adherence to eCTD and NeeS naming
conventions
54. Background
GlaxoSmithKline
GlaxoSmithKline Pharma GlaxoSmithKline Biologicals
Early adopter of the eCTD Late adopter of the eCTD
55. Geographical integration of systems
Current situation
eDMS eDMS
Publishing Publishing
Viewing Viewing
Tracking Tracking
Archiving Archiving