dia european regulatory affairs forum, munich, november 2008
TRANSCRIPT
www.diahome.org
Working in an e-only regulatory environment: An applicant’s experience in Belgium
Marie-Laure FreshardAlain Seront
DIA European Regulatory Affairs Forum, Munich November 2008
www.diahome.org
Who are we?
• Marie-Laure Freshard, viewpoint of the local office– Bristol-Myers Squibb, Regulatory Affairs Belgium
and Luxembourg– BRAS (Belgian Regulatory Affairs Society)
• Alain Seront, viewpoint of the headquarters– Bristol-Myers Squibb Global Dossier
Management / Publishing– EFPIA eCTD Topic Group
www.diahome.org
Agenda
• e-submissions in Belgium: current situation• Initial response to meet NCA requirements• Impact
– Local office– headquarters
• Ongoing changes and improvements• Benefits and concerns• What could have been handled better? What
could be improved?• Conclusion
www.diahome.org
Agenda
• e-submissions in Belgium: current situation• Initial response to meet NCA requirements• Impact
– Local office– headquarters
• Ongoing changes and improvements• Benefits and concerns• What could have been handled better? What
could be improved?• Conclusion
www.diahome.org
Current situation in Belgium
– As from October 2005:– e-submission implemented for
• New registrations• Variations• Renewals• Periodic Safety Update Reports (PSURs) and
Annual Safety Reports (since March 2007)
– Paper submission for• Clinical studies (new Clinical Trial Applications
(CTA) and amendments)
www.diahome.org
Agenda
• e-submissions in Belgium: current situation• Initial response to meet NCA requirements• Impact
– Local office– headquarters
• Ongoing changes and improvements• Benefits and concerns• What could have been handled better? What
could be improved?• Conclusion
www.diahome.org
Initial response of local office
• Initial concern that we did not have the required internal competencies, but…– No supplementary internal resource was required– Interaction with National Competent Authority (NCA) was
excellent thanks to meetings & information sessions, call centre and training materials
– Transition from paper- to e-submission was smooth– Both NCA and applicant learned through experience
• Learning phase lasted +/- 6 months• Our way of working changed gradually
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Initial response of local office
• Additional benefits included:– The national eSubmission guidelines are easy to follow– Non-eCTD electronic Submission (NeeS) can be built manually
thanks to:• A worked example called “Wonderpil” that can be used for practice on
the NCA website• The e-checker available via NCA’s website
– The only new competency needed was in Adobe Acrobat Professional (via internal training)
• But the necessary PDF splitting can be time-consuming
• However, being an early adopter in a small BMS country meant that we could not share experiences with colleagues… – until other countries came “online”…
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Initial response of headquarters
• Where should the NeeS submissions (MRP and National) be prepared? Centrally or by local offices?– By local offices? NeeS prepared by each local
office• Each local office needs to have specialised resources• Each local office needs to have planning and publishing
capabilities• Each local office must track the modifications to the
NeeS format and adapt their processes, retrain their employees
www.diahome.org
Initial response of headquarters
• Where should the NeeS submissions (Mutual Recognition Procedure and National Procedure) be prepared?– Centrally? NeeS prepared by headquarters
• More resources needed at headquarters– Planning and publishing– Interactions with local offices
• But resources are specialised (more efficient), already trained in compiling dossiers, and needed only in 1 or 2 centralised locations
• Maximises resources (when modules 2 to 5 are identical in an MRP)
– One core dossier for all countries + local parts
www.diahome.org
Initial response of headquarters
• Where should the NeeS submissions (MRP and National) be prepared? Decision:– Joint preparation, but centralised finalisation
• NeeS prepared centrally (headquarters) but with input from local offices (module 1)
• Why?– Less impact on resources, globally– Think ahead: the eCTD is going to be prepared by the
headquarters, for all local offices
www.diahome.org
Initial response of headquarters
• New process, new interactions between local office and headquarters– Process before e-submissions (NeeS)
• For national procedure• For Mutual Recognition Procedure• To produce paper submissions
www.diahome.org
Modules 2 to 5 Modules1 to 5
BMS headquartersPrepares common
Modules 2 to 5
BMS local officeAdd local Module 1
Send dossier to local NCA
National Competent Authority1 2
3
+ Mod. 1 PA
PE
R
Mutual Recognition Procedure
Initial response of headquarters
Modules1 to 5
BMS local officePrepare the complete dossier
Send dossier to local NCA
National Competent Authority1
2
PA
PE
R
National Procedure
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2 to 5
Modules2 to 5
2 to
52
to 5
2 to 5
2 to 5
2 to 5 2 to
5
Modules1 to 5
1 to
5
1 to
5
1 to
5
1 to 5
1 to 5
1 to
5
1 to 5
+ Mod. 1
+ Mod. 1
+ Mod. 1
+ Mod. 1
+ Mod. 1
+ Mod. 1
+ Mod. 1
+ Mod. 1
Paper - MRP
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Initial response of headquarters
• New process, new interactions between local office and headquarters– Process for e-submissions (NeeS) and
paper submissions:• For National Procedures• To produce paper and e-submissions• For Mutual Recognition Procedure
– One core dossier, several outputs (NeeS, electronic, paper)
www.diahome.org
National Competent Authority
BMS local officeSend local Module 1 to
HQ1
Modules1 to 5
BMS local officeAdd local Module 12
+ Mod. 1 Modules 1 to 5
National Competent Authority
PA
PE
RN
EE
S
Modules 2 to 5
Local Module 1
Modules 1 to 5
1
BMS headquartersPrepares common
Modules 2 to 5
2
BMS headquartersPrepares common
Modules 2 to 5and local Module 1
3 Send dossier to local NCA
3Send dossier to
local NCA
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1 to 5
1 to 5
1 to
5
1 to
5
1 to
5
1 to 5
1 to 5
1 to
5
1 to 5
11
to 51
2 to 52 to 5
2 to 5
2 to 52 to
5
1 to 5
1
+ Mod. 1
+ Mod. 1
+ Mod. 1
+ Mod. 1
+ Mod. 1
Paper & electronicMRP and National
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1 to 5
1 to 5
1 to
51 to 5
12 to 52 to
5+ Mod. 1
+ Mod. 1
• Why the differences (for module 1 preparation)? Different formats:– Paper / NeeS with PDF TOCs / NeeS
without PDF TOCs
• NeeS: harmonised?
www.diahome.org
Initial response of headquarters
• Create information network with local offices to monitor developments and progress of e-submissions in Europe
• Tools– No new tools – Leverage existing tools (EDMS, publishing system, Acrobat
and plug-ins)– Introduce some new “ways of working” to accelerate the
process of producing e-submissions– Flexibility: keep a flexible approach, keep the processes
“open”
www.diahome.org
Agenda
• e-submissions in Belgium: current situation• Initial response to meet NCA requirements• Impact
– Local office– headquarters
• Ongoing changes and improvements• Benefits and concerns• What could have been handled better? What
could be improved?• Conclusion
www.diahome.org
Impact on local office
Positive impact• Proactive planning (no surprises and submission delays) due to
– NCA notification of forthcoming change and clear guidance– Gradual implementation of the new format
• Time saving– Filing, copying, collating…
• Cost saving– Copying, couriers, binding, transport, office & storage space…
• Increase in operational efficiency– Formatting is always fully compliant thanks to e-checker– Harmonised file naming & format in Belgium– Last minute corrections possible– Following dossier progress now much easier thanks to automated e-mail
tracking– Automated emails can be used as official approval documents– Faster time to approval of type IA, IB variations
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Impact on local office
Neutral/negative impact• System functionality
– No life-cycle management of the complete dossier• No current view (= view of the complete approved
dossier)– No enforcement of the granularity
• National Competent Authority – No impact on frequency of communication with
NCA– NCA review of outstanding paper submissions has
been frozen
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Impact on headquarters
• Authors (clinical, CMC, …): need to take into account the needed granularity (same as CTD/eCTD) when preparing / authoring documentation
• Need to prepare dossiers in several formats and with different contents– Content: different modules 1 (not all forms are marketed
everywhere, specific administrative information in each country)– Formats for MRP: paper + NeeS United Kingdom + NeeS Belgium
+ NeeS standard Netherlands, Spain and Austria• Workload increase for headquarters
– For planning and publishing– We now handle submissions that were done locally in the past
www.diahome.org
Impact on headquarters
• Interactions between headquarters and local offices– More interactions and collaboration
• Exchange of documentation (e.g. module 1 specific documents from local office to headquarters, dossier from headquarters to local office, …)
• More open collaborative electronic workspaces / Document Management System are needed
www.diahome.org
Agenda
• e-submissions in Belgium: current situation• Initial response to meet NCA requirements• Impact
– Local office– headquarters
• Ongoing changes and improvements• Benefits and concerns• What could have been handled better? What
could be improved?• Conclusion
www.diahome.org
Ongoing changes and improvements
Local office in Belgium
• Initially, local office prepared complete NeeS dossier (Modules 1 to 5)– Today, for most dossiers:
• Module 1 (country-specific): Local office• Modules 2-5: headquarters
• NCA has moved towards fully compliant dossiers– Rejections are still subject to a fine (despite e-checker it is still possible to
send non-compliant documents)
• We now use Eudralink for secure dossier posting– Belgian NCA does not have its own secure portal
www.diahome.org
Ongoing changes and improvements
headquarters
• Addition of new “NeeS countries” after Belgium– Need to formalise more the process for
producing NeeS submissions (preparation of user guide / SOP)
– Need to formalise more the relationships between local offices and Headquarters
www.diahome.org
Agenda
• e-submissions in Belgium: current situation• Initial response to meet NCA requirements• Impact
– Local office– headquarters
• Ongoing changes and improvements• Benefits and concerns• What could have been handled better? What
could be improved?• Conclusion
www.diahome.org
Benefits & concerns
• Benefits– NeeS is a step towards eCTD
• Transition to granular submission• Without having to manage life-cycle• Prepare process between affiliate and headquarters for
the eCTD
– Electronic is always better than paper• Quicker to prepare, to review, to consult, to archive• No printing cost (and time)• Less shipping cost from headquarters to affiliates (e-
mail, shared storage area, CD or DVD), and from affiliate to NCA
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Benefits & concerns
• Concerns (at a global level)– No complete harmonisation
• NeeS for Belgium ≠ NeeS for UK ≠ NeeS for the Netherlands – Spain – Austria
• Paper still required in some countries
– Scope of NeeS• Initial scope: transitional format no heavy
investment (tools and processes)• Is it still the case? NeeS as a medium term
format for MRP and/or National?
www.diahome.org
Agenda
• e-submissions in Belgium: current situation• Initial response to meet NCA requirements• Impact
– Local office– headquarters
• Ongoing changes and improvements• Benefits and concerns• What could have been handled better? What
could be improved?• Conclusion
www.diahome.org
What could have been handled better?
• To have made the e-checker available earlier
• Earlier involvement of headquarters• Implementation of a local secured portal
www.diahome.org
What could still be improved?
• Life-cycle management of dossiers– This will come with eCTD
• Implementation of e-submission for clinical trials
www.diahome.org
Agenda
• e-submissions in Belgium: current situation• Initial response to meet NCA requirements• Impact
– Local office– headquarters
• Ongoing changes and improvements• Benefits and concerns• What could have been handled better? What
could be improved?• Conclusion
www.diahome.org
Conclusion
• NeeS:– Like with all change, it seems daunting at first– BUT you will soon wonder how you managed without it
• What is the future (present)? eCTD– Next electronic format for local affiliates (MRP and National
Procedure)?– Another electronic revolution for local offices?
• No: NeeS has prepared the way• Interactions between local affiliates and headquarters will be
the same as for NeeS• BUT: more centralisation of the production of dossiers with
eCTD (more « technical »)
