34.3 The legal basis for medicinal
product marketing
authorizationThe aim of the many directives and regulations been
issued over the years is to harmonize medicine
regulations across EU MS. This harmonization inc-
ludes uniform requirements and decision-making
criteria not only for MA but also for post-marketing
surveillance processes throughout the EU.
The very first Directive issued was Council
Directive 65/65 concerning ‘The approximation
of provisions laid down by law, regulation or
administrative action relating to proprietary med-
icinal products’. It was a milestone in the quest to
provide the same opportunities in healthcare to all
EU citizens, through the removal of local, legal,
technical and regulatory barriers.
Directive 65/65 defined Quality, Safety and Effi-
cacy as the sole criteria for approval of medicines
in the EU, and for awarding MA. It established that
product approvals are granted on purely technical
basis, without political or economic implications.
Ten years later, a pair of Directives extended the
provisions of 65/65. Directive 75/318 defined test-
ing and protocol standards, while Directive 75/319
introduced the Committee for Proprietary Medic-
inal Products (CPMP) and what is now known as
the ‘mutual recognition procedure’ (MRP) for MA
(see below). Nine years later, the structure of the
CPMP was adjusted by Regulation 726/2004, and
now forms the CHMP (see below). These three
fundamental Directives represent the basis of phar-
maceutical regulation that is common to the whole
of Europe; the creation of the EMEA in 1995 (by
Regulation 2309/93, two years earlier) provided
the machinery that implements these Directives.
Most recently, all these relevant legal requirements
for human medicines (other than those foreseen by
Regulation 2309/93, and replacement Regulation
726/2004) have been collected together in Directive
2001/83 entitled ‘Community code relating to med-
icinal products for human use’. This, together with
Directive 2003/63, standardizes the components of
each technical section of the marketing application
dossier for different product categories (such as che-
mical synthesis products, biologics, plasma deriva-
tives, fixed combinations, radiopharmaceuticals,
vaccines, homeopathic, herbal and orphan medicinal
products). European regulations and guidelines that
support the European pharmaceutical legislative fra-
mework are collected in the 10 volumes of ‘The
Rules governing medicinalproducts in the European
Union’, edited by Eudralex:
Vol 1 Pharmaceutical legislation (human)
Vol 2 Notice to Applicants (human)
Vol 3 Guidelines (human)
Vol 4 Good Manufacturing Practices (human and
veterinary)
Vol 5 Pharmaceutical legislation (veterinary)
Vol 6 Notice to Applicants (veterinary)
Vol 7 Guidelines (veterinary)
Vol 8 Maximum residue limits (veterinary)
Vol 9 Pharmacovigilance (human and veterinary)
Vol 10 (forthcoming) Clinical trials34.4 The International
Conference on
Harmonization(ICH) processIn recent years, the pharmaceutical industry has
displayed an increasing tendency to globalize the
market, particularly for innovative medicines. The
differences of requirements in different geographi-
cal areas often caused duplication of clinical trials
or other research, with consequent waste of time
and resources. This added to the escalating costs
and telescoping timelines of research and develop-
ment. Uniformity of approach across the EU has
the potential to eliminate these redundancies. The
Clinical Trial Directive (2001/20, required to be
implemented by MS on May 1, 2004) pursued this
aim further. The Directive requires a uniform
approach toward investigational drug oversight,
creates international standards of pharmacovigi-
lance and establishes a common European adverse
event (AE) database.
Taking these concepts further, it was quickly
realized that even wider international harmoniza-
tion could benefit pharmaceutical research and34.4 THE INTERNATIONAL CONFERENCE ON HARMONIZATION(ICH) PROCESS 445