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Slide1
EU Clinical Trial Regulation(CTR)
Are you prepared
November 2015
A.N. MoultSlide2
Employment Disclaimer
The views and opinions expressed in the following PowerPoint slides are those of the individual
presenter. They
are
brought together as a result in participation in EFPIA Technical Development Expert Group and its Work
Groups however they are not formal EFPIA policy
The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to the company the speaker is employed by (Daiichi-Sankyo Development or any other Daiichi-Sankyo Group companies) Slide3
Contents
CTR status
Stages and their currently projected timings
CTR highlights
One point of application
Consequential legal changes (delegated acts) for IMPs and their status
Areas for clarification and or concernSlide4
Approval & implementation
4
27 May 2014
Q4/2017
(estimate)
Q4/2018*
Q4/2020*
EU-CTD
EU-CTR
Publication
Earliest applicability *
Applicability
Repealed by EU-CTR
A
B
A: Clinical trials may still be submitted and started under EU-CTD
B: Clinical trials submitted under A may continue to be governed by EU-CTD until Q1/2020 (earliest)
Reference: EU-CTR Article 98
*Subject to EMA IT development (EU-CTR Article 82)
17 June 2014
Entry into force
Independent audit of EU Portal & Database functionality published in Official Journal 6-months before applicationSlide5
CTA simplification
Regulation Art. 5, 6, 7 and 8Slide6
Outline
of clinical trial
authorisation (CTA)
dossier content
One
Dossier
Classification as a low-intervention clinical trial
Therapeutic & public health benefit aspects
Risks & inconveniences for the subject
Manufacturing/importation of IMPs/AMPs
IMPD
Labelling
Investigator
’
s brochure
Part I – «General»
Part II – «National»
EU Portal (by EMA)
Content
Submission
Informed consent
Compensation/ rewarding arrangements
Recruitment arrangements
Data protection rules
Suitability of
- individuals
- trial sites
Damage compensation
Biological samplesSlide7
CT Authorisation Concept (simplified
)
Regulation Art. 5, 6, 7 and 8
Dossier (Part I & II)
Submission to EU Portal
Part I Assessment report & conclusion
Confirmation of
rMS
and Validation
45-76 days*
Part II
Assessment
report & conclusion
Default:
No opt-out of
cMS
cMS
accepts positive conclusion of assessment report
Exception:
Qualified opt-out scenarios
Inferior treatment compared to
normal clinical practice
in
cMS
Infringement of national legislation (on use of cells)
Disagreement with conclusion based on safety, data reliability and robustness
Not acceptable
Acceptable
(w/wo conditions)
EU Portal – One Single
decision
per
cMS
and Notification
45-76 days*
Part I – «General»
Lead: reporting MS (rMS)
Part II – «National»
Lead: concerned MS (
cMS
)
Start of Clinical trial Art. 2(25)
rMS conducts review, drafts AR, cMS comment, rMS incorporates input from cMS**
5 days
Conclusion of
national assessment Part II
If no notification
:
Conclusion of
Part I
Assessment report shall be considered the decision
(tacit approval)
10 -25 days
Validation
Assessment
Decision
* Maximal timeline with clock stop for questions.
**
rMS
can extend assessment time by 50 days for ATMPs and products derived from rDNA technology Slide8
Directive v’s CTR additional legal landscape
Legislation / Other document
CTD (2001/20/EC)
CTR (536/2014)
Status
GMP
Directive for MP and IMP
Directive 2003/94/EC
Will be Implementing act for MP – Legal
basis 2001/83/EC and Delegated Act for IMP – Legal basis 536/2014Both under consultation until 24 Nov 2015 - Industry commenting via EFPIA and a draft response has been prepared. Annex 13 Annex 13 A detailed guidance for IMP Under consultation until 24 Nov 2015 - Industry commenting via EFPIA and a draft response has been preparedNIMPCovered by CTR only (as AMPs)Detailed Guidance is not anticipatedSlide9
Some changes to terminology and Trial Definition
Low-
Interventional Clinical Trial
Commercial product within the MA or strict boundaries away from MA
Aimed at Clinical Practice improvement rather than new product / indication
Less stringent rules (at least intended only opinions vary)
Auxiliary
Medicinal Product (covered by Esther). Tip read labelling requirements very carefully.Very easy to miss read and think everything has to be re-labelled Slide10
Areas for clarification and or concern
It is a significant change in the way Clinical Trials are instigated
The portal is taking shape only taking time
Outside of the world of IMP many other functions are undergoing preparations for the changes at a time of significant political pressure on many aspects of health care and drug development.
There are some aspects of the CTR that Industry / EMA (inspectorate) and Commission are now only understanding as demonstrated in the consultation on “delegated acts”, portal etc. for IMP these include
Annex VI. identified early – current status – no change
Inspections outside EU
UK specific – Transitional QPs – ( R. Smith)
In many functional areas questions are being raised and pragmatic solutions found. Slide11
How prepared is your company
Do you have a cross functional preparedness program / initiative
SOPs for all functions
Most companies will be looking at the impacts via SOPs.
Most SOPs will not change or be very minor such as substitution for references - 2001/20/EC to 536/2014.
A significant minority of SOPs will have a major re-write over terminology
A small number of processes will change significantly – Such as around submissions via the EU Portal
Are these identified and plans in place to work differently even if the exact details are not fully known e.g. Portal information –
Worse case - Exactly how it works will emerge around Mid 2017 after the audit or emerging elements may become clear as it is built in 2016.
Slide12
How prepared is your company continued
IMP preparation.
SOP as previous
Annex VI
Even with Annex VI worst case perhaps 80% of studies will not be impacted
Are the 20% identified and what is the cost of mitigation or other changes needed.
If Annex VI does not change waiting to find out may be too late
Is a subset of the preparedness program looking at the Consultation documents – Delegated Act and Detailed Guidance on GMP for IMPs as well as in the GCP aspects of Inspections of Trials by MS’sSlide13
Questions and AnswersSlide14
Clinical trials - Regulatory framework
Transcribed into national law – UK Medicines Act – additional national requirements
Good Clinical Practice
1996
Transcribed into EU Member State law
Declaration
of Helsinki
Good Clinical Practice
Directive 2005Slide15
Understanding EU law
A simple view
A Directive = EU legislation that requires member states to enact via their own legislation the provisions of the directive.
It sets a minimum standard only each member state is allowed to make more stringent provisions as it translates the directive into national law
A Regulation = EU legislation that becomes law in all member states.
It needs no further legislation and is identical in all member states
Delegated act – The What
May be a Regulation or Directive that stems from primary legislation
Are
considered closer to actual law-making The extent of the delegation has to be clearly determined in the original legislation Their content is more likely to be politically sensitive. Implementing act – The HowMay be a regulation or Directive that stems from primary legislationIs considered to be inherently more procedural (templates, procedures, deadlines)A pure, practical implementation of rules that already exist in the original legislation. Slide16
Back up slides
Annex VI
For those who are not aware of EFPIA concerns the video is available.
http://www.youtube.com/embed/5bPZb_Ezg1Y?rel=0
Points to consider in any implementation plans for Annex VI compliance
the type of pack and duration of study including potential for date extension
the time during the one year transition period after Q4 2017 that your company wishes to submit CTA . In addition, you may wish to consider if the choice of timing should be dependent on the pack type / study length or other factors.
if the trial will be ongoing beyond the Q4 2020, which is the earliest point at which all clinical trials in Europe should be compliant with the Regulation. If so will the label strategy be compliant currently or will a change in design mid study be employed?