The roadmap to clinical trial approval in Europe

Edna H.G. Venneker, MD

ReSViNET expert meeting

21 January 2015

Clinical trial approval in Europe

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Multi-national clinical trial applications are assessed in each country:

By several competent authorities (CA)

In parallel or consecutive, up to sponsor

By several ethics committees (EC)

In parallel to CA or consecutive depending on country

Sometimes other relevant parties like local ECs

Each CA/EC reviews the same protocol and often the outcome is a different set of requests for changes which require substantial amendments and another review cycle.

Different ways of submitting: paper vs. electronic, originals vs. copies, different # of copies etc

Some differences

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CTA dossier

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The content of the CTA dossier is defined by each Member State in a different way

Common documents required by all (*content differs per country):

Protocol, IB/SPC, IMPD, Informed consent*

EudraCT form

Insurance*

IMP label*

Locally required documents, e.g.

Protocol or synopsis in local language

ABR form in NL

Independent physician CV in NL

Data protection statements

Some practical aids

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Where to find what is needed for each country:

National health authorities website

detailed information on the process

Information about the documents to be submitted

Ethics committee websites

EFGCP (www.efgcp.eu) for a quick overview of the CTA process and specific requirements in all countries in Europe: The EFGCP Report on The Procedure for the Ethical Review of Protocols for Clinical Research Projects in Europe

http://www.efgcp.eu/

New clinical trial legislation

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New CT Regulation adopted 2 April 2014 and is expected to become effective 15 June 2016

Transition period

For a period of one year trials can be authorized according to the current CT Directive or the new CT Regulation.

Trials already authorized in accordance with the current CT Directive will continue to follow the CT Directive until 3 years after the new Regulation comes into effect.

Under the new Regulation, co-sponsorship is permitted.

Each co-sponsor assumes full regulatory responsibility of the entire clinical trial unless co-sponsors agree otherwise.

New CT regulations: A harmonized application dossier that covers regulatory and EC approval

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Part I: Study specific documents

The concerned MS cooperate in the assessment of scientific, therapeutic and safety aspects

Part II: Country/site specific documents

The assessment is made by each concerned MSindividually and would apply to items such as biological samples, clinical trial agreements, informed consent, recruitment of subjects

Single portal for submission

Depending of sponsor’s preference: can be reviewed in parallel or, alternatively, part I can be reviewed first followed by part II

A national level body will review the documents as per the national applicable law but with one contact point and one fee per country.

Newly added countries only assess part II

Maximum review time 106 days.

The Voluntary Harmonisation Procedure

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For all clinical trials of medicinal products involving two or more EU member states

A single application, submitted to the Clinical Trials Facilitation Group (CTFG) in English

Evaluation in a single procedure by the competent authorities of the concerned member states

Scientific questions on the protocol, IB and IMPD are clarified prior to submission of the CTA

CTA to be submitted to each national competent authority (CA) involved in the VHP

Approval should be provided within 10 days (instead of the 60+ days in the regular procedure).

Data package required for a CTA

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Indication & product dependent

Treatment regimen dependent

Dependent on study phase

In general:

Data on quality (chemistry, manufacturing, control)

Data to support the scientific rationale (indication & target population)

Data to support dose and dose regimen

Literature

Non-clinical pharmacology studies

Non-clinical toxicology studies (single and/or repeated dose acute toxicity, genotoxicity, reprotoxicity, carcinogenicity etc)

Pharmacokinetics

Pediatric Investigational Plan

Types of comments

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Clinical development of preventive vaccines during pregnancy

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The roadmap to clinical trial approval in Europe

Back-up slides

Edna H.G. Venneker, MD

ReSViNET expert meeting

21 January 2015

Timelines CTA submission: regular vs VHP

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