Informa Life Sciences’ Inaugural Conference on e-Submissions

Informa Life Sciences’ Conference on e-Submissions

From paper dossiers to electronic submissionssubmissions

Alain SerontAlain SerontGlaxoSmithKline Biologicals

18-19 October 2011| Zurich, Switzerland

GlaxoSmithKline Biologicals

é19451945

19681968

Founded as RIT (Recherche et Industrie Thérapeutiques)

Becomes SmithKline RIT

19891989

20002000

SmithKline merges with Beecham

GlaxoWellcome and SmithKline Beecham merge20002000 GlaxoWellcome and SmithKline Beecham merge

GSK Biologicals: the vaccine business of GlaxoSmithkline

Over 30 marketed vaccines available worldwide

11.000 employees worldwide / 7000 in thep y /

Headquarter in Belgium

GlaxoSmithKline Biologicals

Manager of the Document Management and Publishing Team at GlaxoSmithKline BiologicalsPublishing Team at GlaxoSmithKline Biologicals

10 years in PharmaR l t tiRegulatory operationsPublishinge-submissions (project management)e submissions (project management)

alain seront@gskbio [email protected]

Topics

Background

Design of the processes and systems for eCTDDesign of the processes and systems for eCTD

Overall process

Content PlanContent Plan

Structure of the electronic document management system (eDMS)

Authoring processAuthoring process

Publishing Process

Viewing and archiving eCTDsViewing and archiving eCTDs

Positive and negative lessons learned

eCTD implementation strategyeCTD implementation strategy

Reusability of documents and submissions

FlexibilityFlexibility

Systems integration

BACKGROUND

Background

GlaxoSmithKline

GlaxoSmithKline BiologicalsGlaxoSmithKline Pharma

Early adopter of the eCTD Late adopter of the eCTD

Background

Start l

eCTDd fEMEA

announced eCTD

mandatory for b i i

implementing new eCTD / NeeS / paper publishing, QC and archiving

First eCTDsequence send

t EMEA b GSK

mandatory for e-submissions

in EU – CP 17 products and >600

ie-submission for Jan. 2010

and archiving tools at GSK Bio

to EMEA by GSK Bio

First worksharing in eCTD submitted

by GSK BIO

sequences in eCTD

December2008

February2009

November2009

January2010

October2011

DESIGN OF THE PROCESSES & SYSTEMS PROCESSES & SYSTEMS FOR ECTDFOR ECTD

It’s not only eCTD (and NeeS)!

From paper dossiers to electronic b i i ?submissions?

oror

From paper dossier to electronic submissions AND paper submission?

Paper submissions are still part of thePaper submissions are still part of the game!

Overall processRegulatory

Affairs / OpsClinical

RegulatoryNonClinical Technical

RegulatoryClinical

I iti t C t tInitiate 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 fromwith docs from

eDMS (following content plan)

Publish

QC (validators + manual QC following content plan)

Submit to authorities

Archive




RegulatoryClinical








Publish



Archive

Content plan

Excel spreadsheet with macros

PurposeLi t ll d t th t i d iList all documents that go in a dossier

with their location in the CTDAnd their order in a specific section

Information on lifecycle for each document

Documents linked in more than 1 leaf

Content plan

PurposeHelp authors to define names for documents and comply with naming conventions

For leaf titlesFor PDF file names

Define documents granularity for each product

Quality check for dossier managers /Quality check for dossier managers / publishers

Content plan

Several content plansGeneric content plan

Product specific content planProduct specific content plan

Submission specific content plan

Dossier specific content plan

Content plan

Several content plansGeneric content plan

Capture GSK principles for all modules regardingCapture GSK principles for all modules regardingGeneral principles of document granularityNaming conventions (leaf title, PDF file name)

Product specific content plan

Capture module 3 principles for a specificCapture module 3 principles for a specific product

Drug substances and drug product presentationProduct specific documents granularity and naming

conventions

Content plan

Several content plansSubmission specific content plan

To reflect modules and documents relevant for aTo reflect modules and documents relevant for a submission type, idependently from a product

E.g. : PSUR submissiongDossier specific content plan

To reflect modules and documents relevant to aTo reflect modules and documents relevant to a specific dossier / submission




RegulatoryClinical








Publish



Archive

Structure of the eDMS


Authoring in eDMS

Communities

Dossier AreaDossier Area


Communities Dossiers Area

electronic document management systemTemplates Communities

Area

Quality

Dossiers Area

Drug Product

Templates Area

Submission Type

Clinical V# Variation II/18

M1 publishing tools

Registration Management

M2

Labeling


3 main areasTemplates area

Templates for most of submission documentsTemplates for most of submission documentsCommunities area

C t i ll th d t f thContains all the documents from the communities which contributes to the dossier writing (Quality CMC, Safety, Labelling, Clinical,writing (Quality CMC, Safety, Labelling, Clinical, ...)

Main storage for “source” documents written for dossiers

Each community has its own folder structure to it d tmanage its own documents


3 main areasDossiers area

Contains all the dossiersContains all the dossiersOrganised by product / submission type / dossierDossier folder structure: CTD or mirrors theDossier folder structure: CTD or mirrors the

composition of the submitted dossierPopulated by linking documents from the p y g

CommunitiesSource area for the publishers to build the

d idossier“Where used?”: for each document, in which

dossier it has been includeddossier it has been included

Authoring

ProcessTake template from templates area

Paste into Community areaPaste into Community area

Link into dossier area

Start authoring in Community or dossier area

CMC: documents not dossier or even product C C docu e ts ot doss e o e e p oductrelated authoring in Community area

Dossiers Managers: document related to a dossier / submission authoring in dossier area

All documents are authored in eDMS




RegulatoryClinical








Publish



Archive

Publishing process

eCTD – NeeS for one product

eCTD – NeeS for several productsS t t f th d iSame content of the dossier

e.g. Worksharing submission

eCTD – NeeS for several regions

Paper only

CTD N S deCTD – NeeS and paper

Publishing process

clone clone

eCTDpublishing tool

eCTDpublishing tool eCTD

publishing tool

eDMS

compile compile compile

0000 (NeeS)

m1

m2

0004 (eCTD)

m1

m2

0006 (eCTD)

m1

m2

0000

m1

m2

m3

m1-toc

ctd-toc

m3

util

index.xml

i d d5 t t

util

m3

index.xml

m3

util

index.xml

m2-toc

m3-toc

index-md5.txt index-md5.txt index-md5.txt

Publishing process

eCTD for different regions clone

eDMS

eCTDpublishing tool

eCTDpublishing tool

il ilcompile

0004 (eCTD)

compile

0006 (eCTD)

m1

m2

m3

util

m1

m2

m3

utilutil

index.xml

index-md5.txt

util

index.xml

index-md5.txt

Publishing process

Paper only

paper

eDMS

paperpublishing tool

p blishpublish

Publishing process

eCTD and paperi timport

eDMS

eCTDpublishing tool

paperpublishing tool

p blish

0004

compile publish

m1

m2

m3

util

index.xml

index-md5.txt




RegulatoryClinical








Publish



Archive

Viewing and archiving eCTDs

eCTD viewerpublishing tools

0001

0000

0001

00000004

0003

0002

0004

0003

0002

0001

0005

0005

0004

eDMS - archivingPublishing temporary

shared drive eDMS - archiving

Viewing and archiving eCTDs

Specific constraintsCurrent view must be available

Historical view must be availableHistorical view must be available

In-progress sequence (not archived yet) must be included in viewerbe included in viewer

Hyperlinks must be functional

From the xml backbone to documentsBetween documents

LESSONS (+ AND -) LEARNEDLEARNED

Lessons learned

Positive aspectseCTD implementation strategy

Reusability of documents and submissionsReusability of documents and submissions improved

FlexibilityFlexibility

Implementation strategy

Implement a system to comply with eCTD technical requirements?

Not a lot of return on investment

CTDeCTDFocus on implementing all theFocus on implementing all the possibilities that eCTD brings?

Focus on how to “use” eCTDFocus on how to use eCTDimplementation to refine and improve our processes and tools?Late adoption our processes and tools?

of eCTD


eC

eDMSPublishing

RP

eDMSPublishingC

Tg

ViewingTracking

PS

gViewingTracking

D Archiving Archiving


0004 (eCTD)m1

MY

m1m2m3utilindex.xmlY

SY

eDMSViewing

index-md5.txt

paperYSTE

ViewingTrackingArchiving

paper

EMS

0000 (NeeS)m1m2m3

m1-tocctd-toc

m2-tocm3-toc

RPS


Implement a system just to comply with eCTD? eCTD as the eDMS / publishingeCTD? eCTD as the eDMS / publishing systems?

If the standard changes the systems mustIf the standard changes, the systems must change

CTDeCTDImplement eCTD as one output from the eDMS / publishing systems?

Reusability of the systems for other outputs

Reusability

Of documents, allowed byChosen granularity (lot of small granules)

Omit context of use in documents (e g noOmit context of use in documents (e.g. no reference to brands, region or type of submission))

Context can be given by

L ti f d t i DMS d iLocation of document in eDMS dossier areaLocation of document in published dossier

Reusability

Of dossierPrinciples

Start with one assembly (generally eCTD / NeeS)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 d idossier

Flexibility

Flexibility

Changes internal to the companyeCTD for new countries (e.g. Switzerland) or new

procedures (e.g. MRP)Outsourcing of some activities?

Changes from regulatory authoritiesChanges from regulatory authoritiesWorksharing and grouping (Jan. 2010)New validation rules for NeeS and eCTD (Sept 2011)New validation rules for NeeS and eCTD (Sept. 2011)eCTD next major version – RPS (some day)

Current processes and systems must accommodate these changesaccommodate these changes

Lessons learned

What could be improved?Systems integration

Systems integration

Repository A

Document management

(lifecycle)Reviewing

Planning

PublishAuthoring

Repository Btracking

Repository DRepository C

Review published

dossierArchive

Distribute (authorities / affiliates)

Systems integration

Document managementReviewing management

(lifecycle)Reviewing

PublishAuthoring

Review bli h dA hi published

dossier

Distribute ( h i i

Archive

(authorities / affiliates)

Systems integration

Management (lif l )Reviewing (lifecycle)Reviewing

Planning

PublishAuthoring


dossier

Distribute ( h i i

Archive


Systems integration

Management (lif l )Reviewing (lifecycle)Reviewing

PublishAuthoring


dossier

Distribute ( h i i

Archive


tracking

Final words

Think what eCTD (or any other new t d d) ld b i t b istandard) could bring to your business

and not only what is the minimum you need to have to comply with eCTD (or any new standard)y )

Final words

Flexibility… flexibility… flexibility

Reusability reusability reusabilityReusability… reusability… reusability

Integration… integration… integration

BACK-UP SLIDES

eDMS and Publishing

For each document in eDMSSome attributes are mandatory

Automatically used to populate attributes inAutomatically used to populate attributes in publishing tools

Are included in eCTD backbone PDF table ofAre included in eCTD backbone, PDF table of contents (for NeeS and paper)

eDMS and Publishing

eDMS Example eCTD NeeS PapereDMSattributes

Example eCTD NeeS Paper

Document name 2.3 - V2011000418 Quality Overall

- - -Quality Overall Summary

eCTD name Quality OverallSummary on h

Leaf title

R f i

Entry in PDF ToC

R f i

Entry in ToC

change manufacturing site

Reference in cross-references to this document

Reference in cross-references to this document

Output file name qos-v2011000418 File name(qos-v2011000418.pdf)

File name(qos-v2011000418.pdf)

-

eDMS and Publishing

Those attributes in eDMSEnsure efficiency

Attributes introduced and checked onceAttributes introduced and checked onceReuse each time the document is used in a

dossierEnsure quality

Content of the attributes are defined by theContent of the attributes are defined by the content plan

Adherence to eCTD and NeeS naming Adherence to eCTD and NeeS naming conventions

Background

GlaxoSmithKline

GlaxoSmithKline BiologicalsGlaxoSmithKline Pharma

Early adopter of the eCTD Late adopter of the eCTD

Geographical integration of systems

Current situation

eDMSPublishing

eDMSPublishingPublishing

ViewingTracking

PublishingViewingTrackingTracking

ArchivingTrackingArchiving


Ideal situation

eDMSPublishingPublishingViewingTrackingTrackingArchiving


Would allow publishing around the clock

Informa Life Sciences’ Inaugural Conference on e-Submissions

Documents

edms dossier areacreate

edms communities link

content planexcel spreadsheet

document documents

t emea

t f th communities

documents relevant

dossier t th t id iwith