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Regulation of clinical trials with medicinal products: Where are we now?

Mariantonia Serrano Castro

Department of Medicines for Human UseAgencia Española de Medicamentos y Productos Sanitarios

(AEMPS)

CMC Strategy Forum Europe 2011 Barcelona, 21st March 2011

Área de Ensayos Clínicos

Basic legislation on CT

Directive 2001/20/CE Parliament and Council, 4th April,

Law 29/2006, 26th July, on guarantees and rational use of medicinal products and M.D. (Law on medicinal products).

Royal Decree 223/2004, 6 February, clinical trials (CT) of medicinal products

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CT Subject CT Subject ProtectionProtection

Guarantees of Guarantees of Quality in the  Quality in the  

ResultsResults

NCAs NCAs cooperation on cooperation on CT assessment CT assessment and inspectionand inspection

TransparencyTransparency

Risks for Risks for environmentenvironment

Legislation Legislation objectives and objectives and

scopescope

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Common Common proceduresprocedures

for Ethics Committee and for Competent Authority CT for Ethics Committee and for Competent Authority CT assessmentassessment

Standard for required notifications and for CT Standard for required notifications and for CT documentationdocumentation

Legislation Legislation objectives and objectives and

scopescope

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EudraLex Volume 10 – Clinical Trials http://ec.europa.eu/health/documents/eudralex/vol-10/index_en.htm

-1 P.&C. Directive + 2 Commission Directives- CT dossier for CA and for EC- Safety rules (SUSAR, DSUR)- Quality of IMP rules (including GMP)- Good Clinical Practice and inspections- Rules for publication of CT- Ethical issues for paediatric CT

Área de Ensayos Clínicoswww.aemps.es

Clinical Investigation

Área de Ensayos Clínicoswww.aemps.es Clinical Investigation

Clinical Investigation with medicinal

productsClinical Trials

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EudraCT No.ProtocolPlan GCP standardsIMP quality standardsInsurance  Single opinion by ECAgreement sponsor‐site for every siteAEMPS authorisationMinistry MARM authorisation (If CT on GMO)

Significant amendments review by EC/AEMPS

CT monitoring (including safety monitoring)SAE/SUSAR reporting

Annual safety report (DSUR)

Public registration of CT

End of trial notification

Results report

Publication of results

Before………………… During............... After….

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EU Clinical Trials RegisterAll paediatric CT and phase II to IV non paediatric

AEMPS CT Data base

National Clinical Trials register (art. 62 Law 29/2006)

TransparencyEU CT application form

EudraCT (EU database on CT on IMP)

Área de Ensayos Clínicoswww.aemps.es Clinical Investigation

Office for supporting

Independent Clinical

Investigation

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Where are we Where are we now?now?

Área de Ensayos Clínicos

636588

665 675 643707

0

100

200

300

400

500

600

700

800

2005 2006 2007 2008 2009 2010

SubdirecciSubdireccióón General de Medicamentos de Uso Humanon General de Medicamentos de Uso Humano

Clinical trials authorised in Clinical trials authorised in SpainSpain

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39694334

50284618

41534491

0

5300

2005 2006 2007 2008 2009 2010

Number of CT applications according to year of loading in EudraCNumber of CT applications according to year of loading in EudraCTTSource: EudraCTSource: EudraCT

Clinical trial applications in Clinical trial applications in the EU the EU

Área de Ensayos ClínicosClinical Trials Facilitation GroupVHP (voluntary harmonization 

procedure)

Simultaneous scientific assessment by the concerned Competent Authorities: CTFG-VHP

• For CT with 3 o more EU countries• Application to the CTFG: Unique CT dossier, single e-application to CTFG, coordinated assessment, single list of questions, 60 days max.• Quick official national application afterwards(authorisation <10 days since a valid application)

CTFG: http://www.hma.eu/77.html

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Where are we Where are we going?going?

11 Legislative changes Legislative changes

22 Operative changes Operative changes

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Where are we Where are we going?going?

11 Legislative changes Legislative changes

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• Cooperation in assessing and following up applications for clinical trials

• Risk‐adapted approach to the procedural aspects of clinical trials

• Ensuring compliance with good clinical practice in clinical trials performed in third countries

http://ec.europa.eu/health/files/clinicaltrials/concept_paper_02-2011.pdf

2012 new Directive

Área de Ensayos Clínicosvolume 10 Eudralex update• Question & Answer (v8 March 2011)• Development Safety Update Report (DSUR) • Guidance on Investigational Medicinal

Products (IMPs) and 'non investigational medicinal products' (NIMPs), rev.1 (March 2011)

• CT-3 guidance on safety and SUSAR reporting (COM Public consultation on 2010)

http://ec.europa.eu/health/human-use/clinical-trials/developments/index_en.htm

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Amendment of Amendment of RD 223/2004 on CT RD 223/2004 on CT 

•• Amend precepts which are Amend precepts which are inconsistent with inconsistent with Commission Commission

CT1CT1 guidance (30th March guidance (30th March 2010) 2010) 

•• Avoid too much detail in the Avoid too much detail in the text in order to make easier the text in order to make easier the adaptation to EU legislative adaptation to EU legislative 

changes in futurechanges in future•• Simplification where possible Simplification where possible •• Update precepts on Ethics Update precepts on Ethics 

CommitteesCommittees(Law 14/2007 on biomedical (Law 14/2007 on biomedical 

research)research)

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Where are we Where are we going?going?

22 Operative ChangesOperative Changes

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EudraCT v8• Submission of CT applications 

without electronic signature• Possibility of submission of any 

CT application/notification (except SUSARs and DSUR) 

• Same validation rules as EudraCT v8 (plus CEIC and  sites)

• CTA form should be filled in EudraCT v8.

Portal ECM• Update of CT application form

• Identification of fields to be displayed in the EU CT register

• CT applications for paediatric CT in third countries (part of a PIP). 

• Multilingual free text fields

• Update of validation rules

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• New legislation• Simplification of procedures• Coordination• Risk based approach• Increase of efficiency• Transparency

Key issues for Key issues for the futurethe future

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aecaem@aemps.esConsultations on clinical trials on

medicinal products

incidensayos@aemps.esProblems/comments on electronic CT

submissions through Portal ECM

Help!Help!

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Thank you very much!aecaem@aemps.es

incidensayos@aemps.es www.aemps.es

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