Criteria for granting a MA refer to quality, safety
and efficacy, which, according to the new law,
‘should enable the risk–benefit balance of all med-
icinal products to be assessed both when they are
placed in the market and at any other time the
competent authority deems this appropriate’.
In fact a MA shall be refused if (article 26):
the risk–benefit balance is not considered to be
favorable
the therapeutic efficacy is insufficiently substan-
tiated by the applicant
the qualitative and quantitative composition is
not as declared
Authorization shall likewise be refused if docu-
ments submitted in support of the application do
not comply with directive requirements.
Article 26 of the Directive and article 17 of the
Regulation also state that ‘the applicant or holder
of the MA shall be responsible for the accuracy of
the documents and of the data submitted’: this
strengthens and formalizes the close relationship
that must exist between Regulatory and Quality
Assurance.
A MA may be renewed after five years, based on
a reevaluation of the risk–benefit ratio, and after
that the MA ‘‘shall bevalid for an unlimited period,
unless the competent authority decides, on justified
grounds relating to pharmacovigilance, to proceed
with an additional five-year renewal.
An authorization will cease to be valid if the
authorized product is not put in the market within
three years after the authorization has been
granted, or if an authorized product is not present
on the market for three consecutive years. Exemp-
tions may be granted on justified reasons.
National application procedure
To obtain a national marketing authorization, an
application is submitted to the competent authority
of the MS. The documentation is the same as
required for the MRP and the technical assessment
should be completed within 210 days. Since
January 1998 independent national applications
are limited to products that are to be authorized
in not more than a single MS.Mutual recognition procedure
The legal basis for this procedure is Directive2001/
83, as amended by Directive 2004/27, which
became mandatory in all MS on October 30,- The procedure requires MS to recognize
assessments done by any one of them, provided
that no risk to the public health can be identified.
Risk to the public health is a broad term, and can
include any quality, safety or efficacy issuewithin a
particular national context. The MRP cannot be
used for all products: the CP is compulsory in
some cases (see below).
Sponsors initially submit their dossiers to a sin-
gle MS. That MS conducts the initial review, and is
termed the reference member state (RMS). When
sponsors then request mutual recognition by other
MS, the latter are termed concerned member states
(CMS). The RMS is selected by the sponsor.
The RA in the RMS then evaluates the dossier
and prepares an assessment report. All being well,
the RMS then grants MA and agrees to the text of a
final SmPC, and the labeling of the product.
Following this initial approval, the RMS will
then facilitate communication between the appli-
cant and the CMS. The CMS may offer comments
and suggestions for changing the SmPC. When
there are opinions that diverge between the RMS
and the CMS, and if efforts to compromise fail,
arbitration may be requested by CMS, or even
(rarely) by the applicant. All CMS must check
the correct translation of the SmPC and labeling
in their national language. The RMS refers an
application to arbitration by the CHMP if needed.
The RMS later handles all post-marketing issues,
such as variations and renewals.
The decentralized procedure
The new Directive (2004/27) introduces a distinc-
tion between the MRP and the decentralized pro-
cedure. The decentralized procedure allows the34.8 PRODUCT REGISTRATION 457