initiated by them but not at the request of a phar-
maceutical company. Outline information about
the trial is required and a decision is made by the
Licensing Authority within 21 days. Where the
product to be used is unlicensed or is complex,
further information may be requested and the
21-day time period is extended.
Clinical trials on marketed products
Where a clinical trial is proposed with a marketed
product, then the applicant can submit a copy of the
trial protocol, provide information on the investi-
gators and, depending on whether or not the appli-
cant is the MA holder, information on the
procedures for reporting adverse drug reactions
(ADRs). It is only possible to use this procedure
for United Kingdom marketed drugs. It does not
apply to unauthorized products manufactured spe-
cifically for trial, nor to products which may be
licensed in other countries but are not in receipt of a
MA in the United Kingdom.
The various member states of the EU were sur-
veyedby Griffin(1987); the United Kingdom, Eire,
The Netherlands and Italy did not have legislation
requiring regulatory approval for studies affecting
human (non-patient) volunteers; in Germany, Den-
mark and Sweden, legislation did impose controls
on such studies. This survey indicated that a clear
definition of what was meant by a ‘human volun-
teer’ was also lacking between national regulatory
authorities in Europe. As clinical trial provisions
vary greatly between EU member states, therefore
the EC, in accord with their prevailing philosophy
of ‘harmonization’, wishes to change this.
With a view to harmonizing the conduct of clin-
ical trials across the EU, Directive 2001/20/EEC
was finally agreed on 14 December 2000, and was
formally adopted in May 2001 with a three-year
transition for its implementation.
TheEUClinicalTrialsDirectivecontainsspecific
provisions regarding the conduct of clinical trials,
including multicenter trials, on human subjects.
It sets standards relating to the implementation
of good clinical practice and good manufact-
uring practice (GMP), with a view to protecting
clinical trial subjects. All clinical trials, including
bioavailability and bioequivalence studies, must be
designed, conducted and reported in accordance
with the principles of good clinical practice.
It defines ‘clinical trial’ as any investigation on
human subjects intended to discover or verify the
clinical, pharmacological and/or other pharmaco-
dynamical effects of one or more investigational
medicinal product(s), and/or to identify any
adverse reactions to one or more investigational
medicinal product(s), and /or to study absorption,
distribution, metabolism and excretion of one or
more investigational medicinal product with the
object of ascertaining its (their) safety and/or effi-
cacy, and it defines ‘subject’ as an individual who
participates in a clinical trial as a recipient of either
the investigational medicinal product or a control.
Thus, healthy volunteer studies are included.
Member states have 60 days to consider a valid
request from an applicant to conduct a clinical
study, in the case of trials involving medicinal
products for gene therapy or somatic cell therapy
or medicinal products containing genetically mod-
ified organisms an extension of a maximum of 30
days may be allowed. If the request to conduct a
study is refused by the competent national author-
ity, the sponsor may on one occasion only modify
or amend the protocol to take account of the objec-
tions raised. No further appeal mechanism is
provided.
Premises where clinical studies are to be con-
ducted are open to inspection by the GCP Inspec-
torate set up by the MHRA in accordance with the
EU Directive on good clinical practice. The inspec-
torate is required to give a preliminary oral report at
the conclusion of the inspection and a written
report within 30 days.
Various sectors of the pharmaceutical industry
have lobbied hard against the Clinical Trial Direc-
tive, particularly the industry based in the United
Kingdom that have objected to the inclusion of
phase I studies involving healthy volunteers
being brought under legislation. These objections
are based on the negative effects on research
conducted in the United Kingdom by CTC scheme
introduced by the Medicines Act 1968, and
the subsequent deregulation achieved by the
CTX scheme had on United Kingdom clinical
research.428 CH33 THE DEVELOPMENT OF HUMAN MEDICINES CONTROL IN EUROPE