Principles and Practice of Pharmaceutical Medicine

A negative effect on phase I clinical research
was being reported in the United Kingdom by
Clinical Research Organisations (CROs) and Aca-
demic University Departments by the Autumn of
2004.

The review of products on the market
pre-1971

At the start of product licensing in the United
Kingdom in 1971, products already on the market
were granted Product Licences of Right (PLRs),
which were subject to review. Between 1971 and
1982, 22 376 lapsed or were revoked or suspended,
and 598 had been converted to full product
licenses. The Committee of Review of Medicines
was deemed to have completed its work in 1991
and was disestablished on 31 March 1992.
All member states of the EC were similarly
required to review the quality, safety and efficacy
data of products on their market. Various dates
were set for the completion of such national
reviews, and the time schedule had to be revised
on a number of occasions due to slow progress of
the exercise. The various national review processes
have not led to harmonized marketing approvals
for these older products within Europe.

Pharmacovigilance and the adverse
reactions voluntary reporting system

One of the most important aspects of the UK
regulatory system is the scheme provided by the
voluntary reporting of adverse reactions to a mar-
keted drug. As most serious ADRs are rare events,
they are unlikely to be detected in early clinical
trials. The problem is essentially one of numbers,
as relatively small numbers of patients are exposed
to a new drug before it is released on to the market.
Marketing may, therefore, be the first adequate
safety trial. The main functions of the adverse
reactions reporting system are:

1. to provide an alerting signal of a risk due to a
   particular drug;
   2. to provide confirmation of an alert detected by
   some other method;
   3. to provide data to assist in the evaluation of
   comparative risks of related drugs.

The spontaneousadversereaction reportingsystem

in the United Kingdom is based on the submission

of ADR reports by doctors and dentists by means of

reply-paid ‘yellow cards’. The system was intro-

duced in 1964 by Professor Witts, the first chair-

man of the Adverse Reactions Subcommittee of the

original Committee on Safety of Drugs (CSD). The

system has continued unchanged to the present

time, and the number of reports and fatal reactions

each year of the scheme’s operation is shown in

Table 33.3.

Membership of the EU and the establishment of

the European Medicines Evaluation Agency

(EMEA) has imposed a European dimension

on ADR monitoring and given it a new title –

‘pharmacovigilance’. The requirements of the Eur-

opeandimension can be summarizedasobligations

for Regulatory Authorities and obligations for the

pharmaceutical company holding a MA:

Agency granted under the centralized procedure (the

Agency referred to is the EMEA) and member state

responsibilities:

Receive all relevant information about suspected

adverse reactions to medicinal products author-

ized by the centralized procedure.

MA holders and member states are required to

provide such information to the Agency.

Member states must record and report to the

Agency within 15 days all suspected serious

adverse reactions.

TheAgencyisresponsibleforinformingnational

pharmacovigilance systems and the establish-

ment of a rapid network for communication.

The Agency shall collaborate with WHO on

international pharmacovigilance issues and

submit information on community measures

33.3 THALIDOMIDE AND ITS AFTERMATH 429