Controlled expression of genes coding for bio-
logically active proteins in prokaryotates and
eukaryotates including transformed mammalian
cells.
Hybridoma and monoclonal antibody methods.
Annex B
Other biotechnological processes.
Medicinal products administered by means of a
new delivery system which, in the opinion of the
competent authorities, constitutes a significant
innovation.
Medicinal products containing a new chemical
entity.
Medicinal products based on radioisotopes.
Medicinal products the manufacture of which
employs a significantly novel process.
This Directive required that products covered by
the Annex classification had to be referred to the
CPMP for an opinion before a MA could be
granted in any member state. This process became
known as the ‘concentration procedure’ or the
‘central procedure’. Products covered by Annex
B could, at the request of the manufacturer, be
dealt with by the concentration procedure or by
an individual national authority, and then achieve
entry into other EU member states markets if
requested by means of the multistate procedure.
In the concentration procedure, the opinion given
by the CPMP was not binding on the member
states.
Directive 2309/93 introduced further changes. It
established a new body that is based in London,
established on 1 January 1994, and two procedures
for the obtaining entry to the markets of the mem-
ber states, namely the ‘multistate or decentralized
or mutual recognition procedure’ and the ‘centra-
lized procedure’; see Figures 33.1 and 33.2, which
show schematically the procedures which became
operative on 1 January 1995.
Under the mutual recognition procedure, the
applicant company would receive a number of
national MAs from national drug regulatory aut-
horities. Under the centralized procedure, the
applicant company would receive a single market-
ing approval from the EMEA, valid in all EU
countries.Table 33.4 The distribution of work to the rapporteur countries under the former CPMP procedure (Directive
75/319/EEC) 1978–1986, and the multistate procedure (Directive 83/570/EEC) 1986 to October 1992
CPMP procedure Multistate procedureCountry Country of origin Recipient country Country of origin Recipient country
Belgium 5 33 14 147
Denmark 7 26 27 106
Germany 5 25 17 195
Greece – 12 0 124
Spain – – 0 144
France 7 15 51 101
Ireland – 24 32 87
Italy – 38 16 142
Luxembourg – 37 0 139
The Netherlands – 35 20 131
Portugal – – 0 38
UK 16 18 75 82
Total 41 263 252 1436
dossiers/applications
33.4 THE EUROPEAN CONTROLS OF MEDICINAL PRODUCTS 433