FEDERAL AGENCY FOR MEDICINES AND HEALTH PRODUCTS F A M

FEDERAL AGENCY FOR MEDICINES AND HEALTH PRODUCTS

Federal Agency for Medicines Federal Agency for Medicines and Health Products

(FAMHP)(FAMHP)

Clinical Trials in Belgium Clinical Trials in Belgium The Role and Function of the National

Competent Authority in a EU environment Competent Authority in a EU environment

26 th August 200726 th August 2007

Greet MUSCHHead of R&D

FAMHP/GM/15/03/2007 1


1 : Innovation in drug discovery and development:Participation of ALL stakeholdersParticipation of ALL stakeholders

ResearchB dBased

PharmaAcademiaHealthcare

professionals

Regulators

PolicymakersSME’s

MS Policymakers

professionalsPatients

gYIC’s

FAMHP/GM15/03/2007 2


2: EU Legal Framework

EU Directi e 2001/20• EU Directive 2001/20• EU Directive 2003 / 94 ( GMP guidance ) • EU Directive 2005/28 ( GCP inspections ) EU Directive 2005/28 ( GCP inspections ) • Eudralex , Volume 10 Notice to Applicants

- Applications for a clinical trial- Safety monitoring and reporting of adverse events- Quality of IMP

Recommendations on inspections- Recommendations on inspections- Additional info ( (N)IMP – non commercial trials )

Website ec.europa.eu/enterprise/pharmaceutical/eudralex

FAMHP/GM15/03/2007 3


2: EU Legal Framework : Directive 2001/20/EC

• Provisions for the conduct of clinical trials on humanbj t i l i di i l d t subjects involving medicinal products

• Compliance to the international recognised ethical andscientific quality requirements ( GCP ) is mandatory

• Exclusive non – interventional trials

•Protection of clinical trial subjects •Protection of clinical trial subjects positive Benefit/Risk balance at any timerights of the subject to physical and mental i t it i d t ti f d t integrity , privacy and protection of data informed consent (minors , incapacitated adults)

•Clinical trials can only start after positive opinion of the y p pEthics Committee and when there is no major objectionraised by the Competent Authority ( Be )

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2: EU Legal Framework : Directive 2001/20/EC

* Suspension of trial / infringements

* Manufacturing , import and labelling of IMP’s

* V ifi ti f li ith GCP/GMP* Verification of compliance with GCP/GMP

* Notification of serious adverse events ( SUSAR’s)( )

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3: National Legal Framework3: National Legal Framework

Law 7 May 2004• Law 7 May 2004• RD 15 July 2004 ( fees )• RD 30 June 2004 ( executive measures )• Circular Letter October 2004 ( some clarifications )• Law 17 November 2004 ( assesment of preclinical data to be

performed by CA )p y )• Law 30 December 2005 ( recognition of EC’s posptponed till 1 September

2006) • RD 18 May 2006 ( GCP inspections )• RD 18 May 2006 ( GCP inspections )• Law June 2006• Law 13 December 2006 and Law 27 December 2006 • Circular Letter January 2007

www.fagg.be ( Geneesmiddelen / Humaan Gebruik / Onderzoek en

FAMHP/GM15/03/2007 6

gg (Ontwikkeling / Klinische studies )


3: National Legal Framework

* L 7 M 2004 l h EU di i * Law 7 May 2004 : larger scope than EU directive all experiments in human where subjects are selected in function of future observations

* Main duties for the Ethics committee ( relevance of the i / l / lifi i f i i d experiment / protocol / qualification of investigator and

facilities / informed consent / ..)

* Main duties for the Competent Authority ( evaluation of chemical-pharmaceutical and pre-clinical data / compliance check with GCP / evaluation of SUSAR’s / ) check with GCP / evaluation of SUSAR s /…)

FAMHP/GM15/03/2007 7


4 : Clinical Task Force

The Clinical Task Force is the Steering Committee assuring and surveilling the g gadequate implementation of the law

related to experiments on human beings related to experiments on human beings. ( 7 May 2004 )

FAMHP/GM15/03/2007 8


4 Cli i l T k F4: Clinical Task Force

Different stakeholders represented :

• Core team:Representative of the Minister of Public Health Pharmaceutical IndustryEthics CommitteesEthics CommitteesCompetent Authority

• On ad hoc basis:Academic ResearchersPhase I units…

FAMHP/GM15/03/2007 9


4 : Clinical Task Force

Strategic meetings on monthly basis :

Strategic Objectives :F ll f ti iti f CA (R&D d t t) d EC’ - Follow-up of activities of CA (R&D department) and EC’s

- Fostering an optimal coöperation between CA and EC’s - IT-strategyIT strategy- Troubleshooting

Organisation of scientific/technical workshopsCommunication via website

f bwww.fagg.be

FAMHP/GM15/03/2007 10


R t ti f th i i t

Clinical Task Force

Representative of the minister

Steering Committee

Stakeholders CA EC’sPharm. Ind. , Ac. Res.

, ...(key representatives)

Local EC’s

Technical Workshops

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Exchange of Scientific/Technical Info( t d i l t d)(not-dossier related)

Other EC’sCA Key EC’s

Clinical Trial Facilitation Group (HoA)p ( )

EC : Ad hoc working group

GCP I iGCP : Inspectors meeting

EMEA ...

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New initiatives from EU Ad Hoc Group CTNew initiatives from EU Ad Hoc Group CT

NfG Ethi f li i l t i l ith hild l d f bli - NfG Ethics for clinical trials with children : released for public consultation

R d ti f l h d l t CT ith high - Recommendations for early phase development CT with high risk compounds ( application form ; time of assessment , need of opinion from Expert Advisory Group ) CHMP FIM guideline comes in operation 1 September 2007CHMP FIM guideline comes in operation 1 September 2007

- Recommendations for optimising the coöperation between EC’s and CA and CA

- Recommendations related to the adequate treatment of reported SUSAR’sreported SUSAR s

FAMHP/GM15/03/2007 13


Clinical Trial Facilitation GroupClinical Trial Facilitation Group

- Workgroups on IMPD , GMP , SUSAR’s : outcome to be reported next meeting

- Systematic discussion of EudraCT Alerts ( lack of efficacy ..)

- Recommendations for early phase development CT : Sharing assessment reports for early phase development CT

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GCP-inspectors group

- SOP’s of GCP inspections on behalf of EMEA :- will be published on their website - will be used as start for writing the SOP’s gre NtoA Vol. 10

- Certification of phase 1 units performing CT with high riskp p g gmedicinal products

- Increased coördination of GCP-inspections within EU andpespecially in 3th countries

- Impact of negative GCP inspectionsp g p

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5: S i tifi T h i l b d K EC’ CA5: Scientific – Technical board Key EC’s-CA

Mandate :Mandate :

To assure the quality of the decision making process with regard to the authorisation and the follow up of clinical trial to the authorisation and the follow-up of clinical trial applications in Belgium .To optimise the scientific / technical interactions between theE hi C i d h C A h i Ethics Committees and the Competent Authority

Core composition :

Representatives of the Key EC’s ( KUL , RUG , UCL, UIA ,ULB , ULG , VUB ) , from AdvComBioEth, from FPHS and from FAMHP, ) , ,

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5: Scientific – Technical board Key EC’s-CA5: Scientific Technical board Key EC s CA

Activities :Activities :

- QA of the decision making processes ( alerts , divergent opinions etc )

- Organisation of scientific/technical workshops : for 2007 :with Rapporteurs designed from different Key EC’s in tandem with theCA

- Paediatric Regulation- Compassionate Use and Medical Need ProgramCompassionate Use and Medical Need Program- Safety reporting- Exploratory CTA’s

Non commercial trials - Non-commercial trials - Substantial amendments- Medical devices

N i t ti l CT

FAMHP/GM15/03/2007 17

- Non-interventional CT


6: Current situation in Belgium Realisations : R&D

- Budget : from 500 € / full application to 1350 € / full applicationll l l- Recrutement : 80 % roll-out versus original plan

- Assessment of pre-clinical data included in the Law - Amendment of the Law by RD for the implementation of GCP-inspections

- Enhanced activities in function of the coöperation with EC’s :IT project interactive website EC’s-CAInfosessions with 35 EC’s ( fully recognised )( minimal performance criteria linked ( pwith remuneration )

Scientific / Technical Board Key EC’s-CA - FAQ’s and Workshops ( published on website www.fagg.be )- KPI’s: 95 % of the CTA applications treated within legal timelines ( risk management approach )

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6 : Trends

d l1: Increased amount of CTA-applications : 2007 : 95 applications / month ( 50 % amendments ) 2004 : 50 applications / month ( 20 % amendments ) 2004 : 50 applications / month ( 20 % amendments )

2: Increased % Phase 1 trials ( FIM ) :2: Increased % Phase 1 trials ( FIM ) :2007 : 26 %2004 : 17 % 2004 : 17 %

3 : Increased % non-commercial trials :2007 : 8 %2004 : 3 %

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6: Trends

4 S f l CT li i i B l i 4: Start of exploratory CT applications in Belgium

5: Increasing demands for regulatory advice for innovative 5: Increasing demands for regulatory advice for innovative trials ( Paediatric Investigation Plans , Advanced therapies, ..)

6: EU legal framework ( Volume 10 EudraLex ) and EC/EMEA working groups installed …g g p

-> harmonisation process still needs further optimisation

> TGN case UK FIM guideline released by CHMP-> TGN case UK FIM guideline released by CHMP-> Reflection on 2001/20/EC at EU level :

3 October 2007

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6: Workplan 2007 GCP- inspections

- Prepararing the design of the Inspection plan 2008 : Q3 2007p g g p p

- Installation of a minimal QA system in function of conducting GCP – inspections in coöperation with P&D department :p p p

-> minimal set on SOP’s-> Peer review related to gradation of findings-> Defining sanctions for non-compliance at macro-level-> Defining sanctions for non-compliance at macro-level

Q3-Q4 2007

Development of a training program for certified GCP inspectors - Development of a training program for certified GCP inspectors Q3 2007

Preparative steps for the integration in the new structure- Preparative steps for the integration in the new structureearly 2008 ?

FAMHP/GM15/03/2007 21


6: National Guidance on Exploratory CT

Answer specific questions about the potential • Answer specific questions about the potential usefulness of substances or the validity of certain targets to treat human diseasetargets to treat human disease

• Questions and program should be adequately defined

• Limited exposure (time dose • Limited exposure (time, dose, number of participants)

• Limited testing

FAMHP/GM15/03/2007 22

• Limited amounts of substance synthesised



bPresubmission

ff b l d- Different substances involved or innovative targets involved: more time needed and involvement of experts

- EC should be involved (delegation of expert)

- Written procedure, electronic, teleconference, formal meeting

FAMHP/GM15/03/2007 23



Q li i d fi d - Quality requirements defined - Preclinical requirements defined :

- Pharmacological inactive dose (microdose Pharmacological inactive dose (microdose approach)

- Pharmacological active dose - Overage approach

in coöperation with Key EC and Research based Pharma in coöperation with Key EC and Research based Pharma - Guidance published : June : pilot phase 6 Months- Guidance presented at CTFG , at PEI/Bfarm Mid September 2007

FAMHP/GM15/03/2007 24


6: CHMP FIM guideline

T i d b TGN UK - Triggered by TGN case UK - Draft CHMP guideline will come into operation 1 September 2007p

- Critical points :- Definition of high risk substances- MABEL approach for starting dose if high risk compound

- Protocol and infrastructure should be adapted to Protocol and infrastructure should be adapted to high risk

FAMHP/GM15/03/2007 25


7 :The way forward …

- Optimisation coöperation with EC’s on permanent basis :Interactive website EC-CA : preparing phase 2

- From Risk management approach to projectmanagement of From Risk management approach to projectmanagement of development programs ( clinical trials ) :Permanent Risk/Benefit monitoring

- Strengthen the scientific expertise ( EMEA think-thank group on innovative drug development )

- Strengthen the position of Belgium at EU level Importance of Early Phase Development in Be

- National Reflection Day Law 7 May 2004 : Mid September 2007

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Many thanks for your attention y y

FAMHP/GM15/03/2007 27

Documents

FEDERAL AGENCY FOR MEDICINES AND HEALTH PRODUCTS F A M