presume CTA approval in the absence of receiving
objections within the 60 days specified by the
Directive. Many regulatory authorities have res-
ponded to the needs of the industry to shorten the
review times and have agreed to review trials in
shorter time periods, for example the MHRA in the
United Kingdom aims to review all CTA applica-
tions for phase I trials within 14–21 days.
Radioactive IMPs
In this special case, additional approval is needed
from the national authorities overseeing radiation
safety. For example, in the United Kingdom this is
theAdministrationofRadioactiveSubstancesAdvi-
sory Committee (ARSAC). Application to ARSAC
only requires a summary of the study protocol, but a
carefulscientificjustificationoftheamountofradia-
tion employed and the number of subjects exposed.
The EU Directive 97/43/EurATOM sets dose limits
for healthy subjects and patients.
Good clinical practices
The European clinical trial directive has the central
objective of protecting subjects taking part in med-
ical research. The principles within Declaration of
Helsinki (as amended) are now integrated into the
legal framework by inclusion in the GCP guide-
lines (and also the GMP guidelines, see next sec-
tion). Briefly, these principles are the following:
Clinical trials should be conducted in accor-
dance with the ethical principles that have their
origin in the Declaration of Helsinki (as
amended), and that are consistent with GCP
and the applicable regulatory requirements.
Before the trial is started, foreseeable risks and
inconveniences should be weighed against the
anticipated benefit for the individual trial subject
and society. [However, the Declaration has a
central tenet that civilians must not be subjected
to undue clinical hazards, without any potential
for benefit themselves, but in order to benefit
society at large.]
The rights, safety and well being of the trial
subjects are the most important considerations
and should prevail over interests of science and
society.The available nonclinical and clinical informa-
tion on an IMP should be adequate to support the
proposed trial.Clinical trials should be scientifically sound and
described in a clear, detailed protocol.The trial should be conducted in compliance
with a protocol that has received ethics commit-
tee(s) and competent authority’s approval.The medical caregivento, and medical decisions
made on behalf of, subjects should always be the
responsibility of a qualified physician or dentist.Each individual involved in conducting a trial
should be qualified by education, training and
experience to perform his or her respective tasks.Freely given informed consent should be
obtained from every subject prior to clinical trial
participation.All clinical trial information should be recorded,
handled and stored in a way that allows its accu-
rate reporting, interpretation and verification.The confidentiality of records that could identify
subjects should be protected, respecting the priv-
acy and confidentiality rules in accordance with
the applicable regulatory requirements.Investigational products should be manufac-
tured, handled and stored in accordance with
applicable GMP. They should be used in accor-
dance with the approved protocol.Systems with procedures that assure the quality
of every aspect of the trial should be implemen-
ted.For a fuller discussion, please see the chapters
specifically on ethics, elsewhere in this book.452 CH34 MEDICINES REGULATION IN THE EUROPEAN UNION