EU Clincal Trial Regulation
Update & Outlook
Dr. Stefan Strasser
Abteilung Klinische Prüfung, Institut Überwachung, AGES MEA
BAG Symposium
27. Januar 2015, Hotel Bern, Bern
Disclaimer
The content of this presentation reflects
knowledge, experience and view of the author.
the
personal
It does not necessarily represent the view of the Federal Agency
for Safety in Health Care (BASG), the Austrian Agency for Health
& Food Safety (AGES), the European Medicines Agency (EMA) or
the European Commission (EC).
Any omission or truncation of regulatory requirements found
within this presentation does not relieve any entity or person of
their legal obligations to fully comply with all applicable
regulatory requirements.
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Clinical Trial Regulation 536/2014
TBD:
- Implementing and Delegated Acts
- Guidelines
http://eur-lex.europa.eu/legal-content/DE/TXT/PDF/?uri=OJ:JOL_2014_158_R_0001&from=EN
http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=OJ:JOL_2014_158_R_0001&from=EN
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Major Impacts of CTR
• One-Stop-Shop for submission and authorisation
• Harmonised Assessment by Member States (MS)
• Single decision per MS (NCA & IEC)
• Centralised portal and database structures
• Transparency – trial information and documents
„public by default“
(with exceptions)
NCA = National Competent Authority
IEC = Independent Ethics Committee
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Submission, Assessment & Decision
Dossier (Part I & II)
Submission to EU
Portal
Part I – Global Aspects
Lead:
Reporting Member State (RMS)
Part II – National Aspects
Lead:
Concerned Member State (CMS)
Confirmation of RMS and Validation
Part I (Draft) Assessment
Part II Assessment
Discussion & Consolidation
List of Questions
List of Questions
Response Assessment & Discussion
Response Assessment
Conclusion
Conclusion
Acceptable
w/wo conditions
Not acceptable
CMS accepts RMS conclusion
or
opts-out
1)
2)
3)
Inferior Rx compared to clinical practice in MS
Infringement of national legislation
Concerns for patient safety or data reliability
CMS combines Part I and Part II decision.
Single Decision per Member State – Notification via EU Portal
„Where the MS has not notified the sponsor […] the conclusion on Part I shall be […] the decision of the MS for
authorisation of the clinical trial.
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Timelines
Validation
Part I
assessment
Part II
assessment
45 days
(+12/+19)
Same as
Part I
5 days
52 days
(+12/+19)
Same as
Part I
N/A
Same as
Part I
5 days (Pt I)
N/A (Pt II)
Decision
Total
Initial CTA
10 days
(+10/+5)
60 days
(max. 106 days)
Additional MS
N/A
52 days
(max. 83 days)
Substantial Modification
6 days
(+10/+5)
38 days
(+12/+19)
49/44 days
(max. 95/90 days)
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Link to EMA information on EU Portal/Database and Functional Specifications:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/01/news_detail_002253.jsp&mid=WC0b01ac058004d5c1
CTR Portal & Databases
Within scope of article 82 specifications & audit.
European Medicines Agency
European Commission
Sponsor
(SUSARs, ASRs)
Eudravigilance
CTM
Member State(s)
Safety Portal
Other Portal
Public
Access
EU Database
Marketing Authorisation Applicant
EU Portal
Workspace
ASR Repository
Data Warehouse
Interface
with MSs
CT systems
Other
data/documents
Out of scope of article 82 specifications & audit.
SUSAR = Suspect. Unexp. Adverse Event
ASR = Annual Safety Report
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EU Portal Roles & Actions
EU single Portal
Submission of CT Dossier
(initial, additional MS or modification)
Submission of Notifications:
- Withdrawal
- Start of trial
- First Visiit first subject
- End of recruitment
- End of trial (in each MS, All MS,
Global)
- Temporary Halt
- Restart of the trial
- Early termination
- Serious Breaches
- Unexpected Events which affect
Risk/Benefit
Submission of Union Control Reports
Commision
Selection RMS (Part I)
Notification of validation
(initial, additional MS or modification)
Submission Part I Conclusion
MS
Sponsor
Communication on corrective measures
Submission Inspection Information
Submission of clinical summary report
Submission of Serious Breaches of
GCP or the Regulation
Update of CT information/
Non substantial modifications
Single Decision notification
Submission of Clinical Study Report
MA Applicant
EU
Database
Search and view public information
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Link to Public Consultation Website of the EMA:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/01/news_detail_002253.jsp&mid=WC0b01ac058004d5c1
Database Information & Transparency
Trial-Related
Product-Related
After decision/
when submitted
Major characteristics
Protocol summary
Conclusion on part 1
Decision on the trial
Substant. modifications
Notifications
Summary of Results
Major characteristics
After marketing
authorisation*
Trial protocol
Patient Information
List of Questions (excl. Q)
Responses (excl. Q)
Clinical Study Report
Investigator‘s Brochure
IMPD (excl. Q)
List of Questions (Q)
Responses (Q)
IMPD (Q)
(after decision, if authorised)
* Details under discussion
No publication
Public consultation currently open (until 18.02.2015) 9
The Austrian Situation (2014)
Federal Office for Safety in Healthcare (BASG) – Austrian NCA
BASG
250 trials
Assessment / Regulatory
Paper
1000
modifications
1200
notifications
Administration / Validation
Data Medium
(CD/DVD)
National Clinical Trial Database
Based on EudraCT XML
not public
silent approval after 35d, flexible timelines for GNAs, direct contact with applicants/sponsors
Ethics Commitees (IEC)
Federal Ministry of Health (BMG)
BMG
7 lead ethics committes
About 20 local IECs
For Gene Therapies!
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Outlook on the National process
Challenges
Possible Solutions
Providing the required expertise
IEC to be involved in Part I and Part II
CT and MA assessors working together
Harmonisation of NCA and IEC
Common process for NCA and IEC
Communication only via EU Portal
National IT system for NCA and IEC
with interface to EU Portal/Database
Timelines
IT-supported management of
documents, workflow and timelines
Optimising of administrative and
assessment processes (e.g. templates)
Change of IEC structure???
Transparency
Restriction of uploaded information
where possible
MA = Marketing Authorisation (including Scientific Advice)
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Dr. Stefan Strasser
[email protected] | www.basg.gv.at
Thank you for your attention!
Questions?