national level is often quicker to obtain, and the
costs are considerably lower than that for the
CHMP. However, national authorities will decline
to give scientific advice when it has also been
requested from the CHMP, viewing the effort as
duplicative and redundant.
34.8 Product registration
European controls on medicinal products were
originally laid out in Directive 65/65, but it was
Directive 75/319 that established the CPMP as the
pivotal review committee within the EMEA. With
the major revision of the medicines regulation and
the enlargement of the EU to 25 MS in May 2004,
the CPMP has now been restructured, and renamed
as Committee on Human Medicinal Products
(CHMP). The CHMP now comprises a representa-
tive from each MS, as well as nonvoting represen-
tatives from the EEA countries (Norway, Iceland
and Liechtenstein). Currently, the CHMP meets
during the third week of each month at the
EMEA headquarters in London.
The format of the submission dossier and the
technical requirementsare thesame in all cases: the
CTD has been made compulsory in Europe for all
submissions since 2003.
The common technical document
The CTD format is described in ICH Guidance M4,
and is organized in the following five modules (see
also Figure 34.2):
Module Iis specific to the region in which the
application is made (the EU in this case) and is,
technically, not part of the CTD. It contains
regional administrative information, a submis-
sion table of contents, the SmPC (i.e. the draft
package insert), the patient information leaflet
(PIL) (if any) and translation of the labeling into
all relevant languages (in the case of a CP appli-
cation this is now required in 22 languages).
Module IIcontains the CTD summaries. These
are introduced with a table of contents for
Modules II–V and an introductory document.
The summaries cover manufacturing and quality
control, nonclinical information (including tox-
icology) and a clinical overview (comparable to
the ‘expert report’ in previous forms of European
submissions).Module IIIcontains the detailed manufacturing
and quality data: it starts with its own table of
contents, and then continues with the organized
body of data and any applicable literature refer-
ences.Module IV contains the nonclinical study
reports. Like Module III, it has its own table of
contents, and then all the study reports and rele-
vant literature references.Module Vthen contains the clinical study reports- again starting with a table of content for the
module. A tabular summary of the studies is
useful when inserted before the study reports
themselves.
For most applications, English can be used for
Modules II–V. However, for national applications,
some authorities require a national language and
should be checked with the RAwell in time before
submission. The EMEA web site provides admin-
istrative details concerning submissions, such as
formats for electronic submission in each MS,
numbers of hard copies required and so on.Marketing authorization
Directive 65/65 established that a medicinal pro-
duct can only be marketed after being authorized
by the competent authority. Such obligation is
reiterated in article 6 of Directive 2004/27 and
article 3 of regulation 726/2004.
Regulation 726/2004 covers biotech products
and other innovative products as specified in the
relevant annex; main consequences of the changes
of this regulation will be introduced in the chapter
relating to CP.
Article 2 of Directive 2004/27 states that ‘this
Directive shall apply to medicinal products for34.8 PRODUCT REGISTRATION 455