significant new administrative aspect: every appli-
cant for a CTA, in any EU MS must now have a
legal representative who is domiciled in Europe,
through whom all activities and communications
pass. Non-European applicants for a CTA must,
therefore, name a representative, resident in the EU
(this includes Swiss study sponsors, and there is an
analogous requirement in the United States).
The pan-European clinical trial database
(EuDRACT)
The EuDRACT enables the various European
regulatory authorities to track all clinical trials tak-
ing place anywhere in the community using a single
source of information. Every clinical trial in the EU
must be registered with this database and has a
unique registration number (the EuDRACT trial
number), even when the study is taking place in
multiple EU countries. Sponsors can register their
clinical trials online, and must have a system in
place to guarantee that duplicate EuDRACT num-
bers are not requested. The EuDRACT database is
for the sole use of RAs and its contents cannot be
accessed by trial sponsors or the general public.
The information that needs to be provided about
the clinical trial at the time of registration in
EuDRACT is similar, but less extensive than that
provided in the CTA and includes the following:
The title of the trial
The identity of the sponsor
The type of application
The trial monitoring and central facilities
Information about the IMPs
Information about the placebo
The manufacturer or importer of the IMPs
Information about the trial design and procedures
Details of the trial subjects;
Information about the overseeing ethics
committee
The applicant has no access to the information, once
it has been registered with the database; only the
regulatory authorities can alter the database.Ethics committees
Directive 2001/20 has also led to a set of detailed
Guidance documents, to help MS interpret the
Directive and implement appropriate ethical
committee oversight. The ‘Detailed Guidance on
the Application Format and Documentation to be
Submitted in an Application for an Ethics Commit-
tee Opinion on a Clinical Trial for a Medicinal
Products for Human Use’ (April 2003) is self-
explanatory. This document includes a table that
collates each special requirements of MS, and it is
designed to be used with the national Guidances,
where they exist.
All proposed clinical trials in Europe now have
to receive an affirmative favorable opinion from a
properly constituted ethics committee, before
commencement. In the case of multinational, mul-
ticenter trials, only a single ethics committee opi-
nion is neededin each MS. There is nonetheless the
capability for individual sites, with additional
ethics committees, to reject a clinical trial. But a
negative opinion from the local ethics committees
would only stop the trial at the particular site, and
not affect the overall approval given from the lead
ethics committee in the relevant MS.
Both sponsors and investigators are empowered to
apply for the ethics committee opinion. The Directive
states that the applicant can choose to make parallel
applications to the NCA and the ethics committee, or
do it sequentially. However, in practice national pre-
ferences will vary in whether sequential applications
may be preferred. It is important to make sure that the
version of the reviewed documents at the ethics
committee and the RA match.
The National Competent Authority and ethics
committee initially validate the application and the
sponsor is informed that the application is valid (i.e.
the format is appropriate and that the application
appearsprima facieto be complete and accurate).
Ethics committees have the same review clock as
regulatory authorities, including the special situa-
tions with extended or eliminated timeframes (see34.6 CURRENT EUROPEAN REGULATORY PRACTICE 449