During the period 1971–1981, after the imple-
mentation of the Medicines Act (1968), the Licen-
sing Authority granted 204 MAs for new chemical
entities (NCEs), granted 3665 marketing approvals
for new formulations and 6898 variations of mar-
ketedformulations(GriffinandDiggle,1981).Inthe
period 1971–1994, there were 525 NCEs approved
for marketing, 30 new biological entities (NBEs)
and 28 products of biotechnology (Jefferyset al.,
1998). Of these new active substances, 35 product
licenses were surrendered bythe manufacturersand
a further 22 were withdrawn for safety reasons.
National MAs were intended to be phased out
after 1 January 1998, but it is likely that national
approvals for marketing will continue beyond that
date. The future foresees that all MAs within the
European Union (EU) will have been issued under
the rules governing medicinal products in the EC
by virtue of the centralized procedure or the so-
called ‘mutual recognition’ or ‘decentralized pro-
cedure’ (vide infra).
Controls on conduct of clinical trials
in the United Kingdom
In the United Kingdom, when the Medicines Act
(1968) came into operation, all clinical trials in
patients had to be covered by a clinical trial certi-
ficate (CTC). Under the Medicines Act, studies on
normal healthy human volunteers (phase I studies)
were exempt.
A clinical trial in the terms of the Medicines Act
(1968) is an investigation, or series of investiga-
tions, consisting of the administration of one or
more medicinal products, where there is evidence
that they may be beneficial to a patient by one
or more doctors or dentists for the purpose of
ascertaining what effects, beneficial or harmful,
the products have. The Licensing Authority does
not lay down rigid requirements concerning the
data, which must be provided before authorization
can be given for the clinical trial of a new drug. It
issues guidelines for applicants.
By the late 1970s, it had become apparent that
the need to apply for a CTC and the regulatory
delay that this caused was driving clinical research
out of the United Kingdom. The Secretary of State
for Social Services approved the introduction of a
new scheme in 1981, the details of which were
announced by Griffin and Long (1981). The new
procedures allowed for a clinical trials exemption
(CTX) from the need to hold a CTC; the applicant
company was required to produce a certified sum-
mary of data generated to support the proposed
clinical studies, signed by a medically qualified
advisor or consultant to the company. The regula-
tory authority has 35 days to respond to the notifi-
cation, but can in exceptional circumstances
require a further 28 days to consider the notifica-
tion. If the CTX is refused, the applicant can apply
for a CTC, in which circumstances complete data
have to be filed. If the CTC application is refused,
the statutory appeal procedures come into play if
the applicant company wishes to avail itself of this
provision. These appeal procedures are identical
with those for marketing applications.
The basis of the CTX scheme is that, together
with a detailed clinical trial protocol, summaries of
chemical, pharmaceutical, pharmacological, phar-
macokinetic, toxicological and human volunteer
studies may be permitted instead of the additional
details normally required for a CTC or product
license application. This CTX scheme is based on
the requirement that (a) a doctor must certify the
accuracy of the data; (b) the supplier undertakes to
inform the Licensing Authority of any refusal to
permit the trial by an ethical committee; and (c) the
supplier also undertakes to inform the Licensing
Authority of any data or reports concerning the
safety of the product.
Speirs and Griffin (1983) described the effect of
the CTX scheme in attracting clinical studies on
NCE in the first year of operation of the scheme. In
1980, there were 87 applications for CTC; in 1981,
the first year of the CTX scheme, there were 210
applications for CTX, of which 79 were for NCEs.
Speirset al. (1984) studied the effects of the CTX
in encouraging inward investment into research in
the United Kingdom; 23 companies had increased
their research investment by 100%.Doctor’s and dentist’s exemption
This is an exemption which is available to doctors
or dentists who are undertaking clinical trials33.3 THALIDOMIDE AND ITS AFTERMATH 427