Principles and Practice of Pharmaceutical Medicine

In case that an article 29 referral (mutual recogni-
tion referral) relates to a product with MA in MS
other than those involved in the procedure, a new
article 30 referral can be triggered for those MA to
pursue harmonization of the SmPC. This is also
applicable to cases where a MA is pending for the
product submitted to referral: the MS are obliged to
grant or reject the MA in conformity with the
community decision. Subsequent applications for
the same medicinal product must follow the com-
munity decision and use the harmonized SmPC.

Stopping of the referrals

In case of article 29 referral (a mutual recognition
referral), an application may be withdrawn by the
applicant at any time in any MS where it has been
submitted. This action may avoid the referral.
However, if an issue of community interest is iden-
tified, MS or the Commission may then start an
article 31 referral.
For referrals relating to articles 30, 31 and for
follow-up referrals, the procedure can only be
stopped if the applicant/MAH withdraws the con-
cerned product from all the EU markets. In such
case the CHMP may decide to close the referral
procedure, or to proceed in spite of the withdrawal,
where public health issues are considered to need
continuing discussion.

Unilateral actions by MS in urgent cases

MS may take unilateral urgency measures, such as
suspending the marketing and use of a medicinal
product, whenever such action is deemed neces-
sary to protect public health, and until a final deci-
sion is adopted. EMEA must be informed on the
following working day, and the matter is discussed
in the following CHMP meeting. A referral proce-
dure, where appropriate, may be triggered by either
a MS or the Commission.
Overall, these procedures have not been exten-
sively used. As to article 29 referral, applicants
have preferred, in most cases, to withdraw the
application in the countries unwilling to accept
the mutual recognition, rather than go through the

CHMP arbitration and face possibly unfavorable

consequences.

However, it should be remembered that such

procedures have to be regarded in the perspective

of the general scope of achieving the highest possi-

ble degree of harmonization within the community.

34.9 Orphan medicinal products

Orphan medicinal products are defined as those

diagnosing, treating or preventing life threatening

or very serious conditions that affect no more than

5 per 10 000 persons in the EU.

Regulation EC 141/2000 established the COMP

formed by one representative from each MS, three

from various patients groupsand three from EMEA

to liase with CHMP. The role of COMP is to

help sponsors to prepare orphan designation

applications through free pre-submission meet-

ings;

provide scientific advice on the development of

the product after orphan designation has been

granted;

examine applications for designation of orphan

drug status and

assist the European Commission on develop-

ment of orphan drug policies.

The incentives for orphan products are: market

exclusivity for 10 years after the marketing author-

ization even if a previously authorized product is

now developed for a new orphan indication; PA

(scientific advice on development and dossier pre-

paration); access to the centralized registration

procedure; fee reduction for all types of regulatory

activities (applications review, inspections, varia-

tions, scientific advice, etc.) and provide a limited

amount of EU-funded research grants for orphan

products.

Orphan designation can be applied for at any

stage of the development with appropriate scienti-

fic justification. The designation of an orphan pro-

duct is preliminary to application for a MA and

34.9 ORPHAN MEDICINAL PRODUCTS 465