Principles and Practice of Pharmaceutical Medicine

been achieved on a particular product already
submitted to a community procedure and a
MS considers that a change/variation, suspension
or withdrawal of a harmonized MA may become
necessary for protection of public health. Likewise,
by reference to article 5(11), 6(12), 6(13) of
Regulation 1084/2003, one or more MS may
not recognize a draft decision of the Reference
MS on a variation. In this case, therefore, the
CHMP will issue an opinion on the variation to
the terms of a MA, its suspension or withdrawal,
where such actions are justified by public health
issues.
These referrals may be started by the MS or the
MAH.

Procedure

To start a referral procedure different forms must
be used, according to the type of referral; such
forms are annexed to the Guideline included in the
Notice to Applicant Volume 2A – Procedures for
Marketing Authorization – Chapter 3 – Community
Referral – February 2004.
Before starting a referral procedure a notifica-
tion should be sent to the EMEA, stating

the intention to submit a referral;

information on the medicinal product con-
cerned;

clear and concise formulation of the questions to
be discussed;

proposal on the documentation to be provided;

where appropriate, request for ameeting with the
EMEA to deal with issues linked to the referral.

The scientific opinion on the referral questions will
be provided by the CHMP and all the pertinent
documentation should be submitted by the MS or
applicant/MAH.
Where the referral follows the suspension or
withdrawal of a product from the market in a MS,
this MS should immediately inform the CHMP

members, the authorities of the other MS and the

EMEA of the action taken.

If the referral is started by an applicant/MAH,

the documentation submitted should include the

expert reports updated with the data supporting

the reasons for referral.

Timeframe for the referral

The CHMP issues a reasoned opinion within

90 days of the referral. This period may be

extended to 180 days in case of articles 30, 31, 36

and 37 referrals. The timetable is described in

detail in Volume 2A of the above guideline.

The clock of the procedure may be stopped to

allow the applicant to prepare explanations, to be

submitted or discussed in a hearing.

The opinion of the CHMP may be subject to

appeal; the intention to appeal should be notified

to the EMEA within 15 days after the opinion has

been issued, and within 60 days the detailed

grounds for appeal must be forwarded to the

EMEA. A final opinion will be adopted by the

CHMP within the following 60 days, together

with an assessment report, stating the reasons for

the conclusions reached. In the event of an opinion

in favor of granting or maintaining a MA the opi-

nion will include a draft SmPC, the proposed label-

ing and any condition deemed to be relevant for the

safe and effective use of the product. This opinion

will be sent within 15 days to MS, Commission and

the applicant/MAH.

The subsequent Commission’s decision-making

procedure is essentially the same as for the CP. But

the decision is not only addressed to the applicant

but also to the MS concerned in the referral, who

are required to take actions, such as grant, suspend

or withdraw a MA, as established in the decision

within 30 days following its notification. The MS

are also required to inform the Commission and the

CHMP of the measures taken.

Consequences of the decision

The decision following a referral is only applicable

to the products and MS involved in the procedure.

464 CH34 MEDICINES REGULATION IN THE EUROPEAN UNION