1. Regulation EU 536/2014 on clinical trials
Stéphanie Crosetto
14/11/16
Master AREIPS – Regulatory Seminar

2. Summary Introduction on clinical trials Regulation EU 536/2016
Main changes
Timeline for the deposit
Pilot phase of the ANSM

3. Introduction on clinical trials

4. Definitions
Art. L of the Public Health Code defines the term : biomedical research
«  Research organised and practiced on human beings for the developpement of biological or medical knowledge »
Sponsor : individual, company, institution or organisation which takes responsibility for the initiation, for the management and for setting up the financing of the clinical trial.

5. The history of regulation
1988 : Huriet-Serusclat law
2001 : Directive 2001/20/CE
2004 : Public Health law
2012 : Jardé law
2014 : Regulation EU 536/2014

6. Impact of the regulation
Between 2007 and 2011 :
Increase of the costs of in EU and lack of harmonised legislation
Increased time of response (up to 121 days for approval)
Decline of clinical trials in EU by 25 %
From 5 000 to 3 800 authorisations delivered
Mostly because of ethical commities vs 60 days in the US

7. Regulation EU 536/2014
Direct application into the french legislation and repeals the Directive 2001/20/CE

8. Categories of clinical trials
With the Directive 2001/20/CE :
Biomedical research
Routine care study
Non interventional study
With the « Jardé » law : based on the risk
Interventional study
Minimal-risk interventional study
Non-interventional study

9. Main changes 3 new types of studies : Clinical trial
Low-intervention clinical trial
If used in accordance with the terms of the marketing authorisation
If the use is evidence-based and supported by published scientific evidence
Non-interventional study

10. Main changes Tacit answer at the end of the procedure
Subsequent addition of a new MS is possible (art. 14)
Cluster trials (art. 30)
For low-interventional clinical trial into one MS
Co-sponsorship is possible (art. 72) with shared responsibility
Official journal of the European Union (27/05/2014)

11. Other changes Early termination of the clinical trial (art. 37)
Within 15 days from the end of the clinical trial
For reasons of subject safety
Serious adverse events reporting (art. 41)
Transparency of the results : available on the EU data base (art. 81)
The notification shall be made within 15 days from the end of the clinical trial
Anonymised data are visible by all people one year after the end of the clinical trial. All data on medicinal products without an marketing authorisation

12. Main changes Submission of one application dossier for all MS (art. 1)
Part I
Cover letter
EU application form
Protocol
Investigator Brochure
Documentation relating to compliance with GMP
EM Dossier
Auxillary medicinal product dossier
Scientific advice and PIP
Content of the labelling
Part II
Recruitment arrangments
Subjects information
Suitability of the investigator and facilities
Proof of insurance cover
Financial and other arrangements
Proof of payment of fee
Proof of compliance of data processing
Part II for each MS
(Annex I)

13. Timeline for the authorisation
Validation
Choice of the reporting MS if several Concerned MS
Validation of the application dossier completeness
10 days
Assessment
Separated assessment of part I and II
45 days
Notification
Informs the sponsor through the EU portal
5 days
Total of 60 days

14. Timeline for the authorisation
Validation
Choice of the reporting MS if several Concerned MS
Validation of the application dossier completeness
10 days + 15 days
Assessment
Separated assessment of part I and II
45 days
+ 31 days : additional information from the sponsor
Notification
Informs the sponsor through the EU portal
5 days
Worst case
50 days for the purpose of consulting experts
Total of days
+ 50 days if advance therapy medicinal product

15. Timeline for the authorisation
Notification of the sponsor (art. 8):
Authorisation of the clinical trial
Authorisation subject to conditions
Refusal
 Unique authorisation at the national level
Valid for 2 years in the CMS
To the date of the first recruitment. If this date is outdated, the autorisation becomes null

16. Cases of refusal by a MS Part I Part II
Evaluation report is unfavourable
A MS desagrees with the evaluation report
Part II
Part II is non-complying
Unfavourable opinion a ethics commity

17. Pilot phase of the ANSM

18. Pilot phase It concerns CT on medicine All phases of CT (I to IV)
All therapeutic areas
Initial autorisation only
All sponsors (academic and private)
Volontary ethics committee

19. Pilot phase Cases that doesn’t fall into the scope of the pilot phase:
CT other than on medicines (medical devices, in vitro diagnostics, cosmetics a,d labile blood products)
Advanced medicines
Running of the CT
In parallel and simultaneous deposit to the Agency and ethics commitee
through Eudralink
5 product directions are volontary for this pilot phase

20. Conclusion Simplified and harmonised procedures within the EU
To restaure the EU competitivity
Will be in application in 2018 : « Touraine » law in the meantime

21. Thanks for your attention