HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN"L 150/68
EN
Official Journal of the European Union
9.6.2012
COMMISSION REGULATION (EU) No 488/2012
of 8 June 2012
amending Regulation (EC) No 658/2007 concerning financial penalties for infringement of certain
obligations in connection with marketing authorisations granted under Regulation (EC) No
726/2004 of the European Parliament and of the Council
THE EUROPEAN COMMISSION,
Commission may impose financial penalties for
infringement of its provisions or the implementing
Having regard to the Treaty on the Functioning of the European
measures adopted pursuant to it in relation to
Union,
medicinal products authorised through the procedure
laid down in Regulation (EC) No 726/2004. It also
empowers the Commission to adopt measures
Having regard to Regulation (EC) No 726/2004 of the European
concerning the maximum amounts of those penalties
Parliament and of the Council of 31 March 2004 laying down
and the conditions and methods for their collection.
Community procedures for the authorisation and supervision of
Since Regulation (EC) No 658/2007 concerns financial
medicinal products for human and veterinary use and estab
penalties for infringement of certain obligations in
lishing a European Medicines Agency ( 1 ), and in particular the
connection with marketing authorisations granted under
first subparagraph of Article 84(3) thereof,
Regulation (EC) No 726/2004, it is appropriate, for
reasons of consistency, to include in the scope of Regu
lation (EC) No 658/2007 the obligations provided for in
Having regard to Regulation (EC) No 1901/2006 of the
Regulation (EC) No 1901/2006 whose infringement may
European Parliament and of the Council of 12 December
give rise to financial penalties under that same Regu
2006 on medicinal products for paediatric use and amending
lation.
Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive
2001/83/EC and Regulation (EC) No 726/2004 ( 2 ), and in
particular Article 49(3) thereof,
(3)
In view of the harmonised application of the obligations
laid down in connection with marketing authorisations
Whereas:
granted under Regulation (EC) No 726/2004 and of the
need to ensure the effectiveness of those obligations, the
interests of the Union are involved where those
(1) Regulation
(EU)
No
1235/2010
of
the
European
obligations are infringed. Moreover, pharmacovigilance
Parliament and of the Council ( 3 ) amended Regulation
rules are necessary for the protection of public health
(EC) No 726/2004 as regards pharmacovigilance of
in order to prevent, detect and assess adverse reactions
medicinal products for human use in order to strengthen
to medicinal products for human use placed on the
and rationalise the monitoring of the safety of medicines
Union market, as the full safety profile of medicinal
that have been placed on the market in the Union. The
products for human use can be known only after they
provisions of Regulation (EC) No 726/2004 are comple
have been placed on the market.
mented by Directive 2001/83/EC of the European
Parliament and of the Council of 6 November 2001
on the Community code relating to medicinal products
(4) Infringements
in
relation
to
veterinary
medicinal
for human use ( 4 ) which has been amended by Directive
products are not concerned by Regulation (EC) No
2010/84/EU of the European Parliament and of the
1901/2006 or the amendments as regards pharmacovigi
Council ( 5 ) as regards pharmacovigilance. In order to
lance. The scope of Regulation (EC) No 658/2007
ensure the enforcement of the obligations relating to
therefore does not need to be modified in this respect.
pharmacovigilance introduced by Regulation (EU) No
However, in order to ensure consistency with the
1235/2010 and Directive 2010/84/EU, it is necessary
amended provisions and to improve clarity, it is appro
to adapt Commission Regulation (EC) No 658/2007 of
priate to restructure certain provisions concerning
14 June 2007 concerning financial penalties for
veterinary medicinal products without altering the
infringement of certain obligations in connection with
substance.
marketing authorisations granted under Regulation (EC)
No 726/2004 of the European Parliament and of the
Council ( 6 ) so that any infringement of those obligations
(5) The
amended
provisions
shall
apply
as
of
the
same
date
may be subject to the financial penalties provided for in
as the amendments by Regulation (EU) No 1235/2010 as
Regulation (EC) No 658/2007.
regards pharmacovigilance.
(2) Regulation
(EC)
No
1901/2006,
as
amended
by
Regu
(6) Regulation
(EC)
No
658/2007
should
therefore
be
lation (EC) No 1902/2006
( 7 ), provides that the
amended accordingly.
( 1 ) OJ L 136, 30.4.2004, p. 1.
( 2 ) OJ L 378, 27.12.2006, p. 1.
(7) The
measures
provided
for
in
this
Regulation
are
in
( 3 ) OJ L 348, 31.12.2010, p. 1.
accordance with the opinion of the Standing
( 4 ) OJ L 311, 28.11.2001, p. 67.
Committee for Medicinal Products for Human Use and
( 5 ) OJ L 348, 31.12.2010, p. 74.
( 6 ) OJ L 155, 15.6.2007, p. 10.
the Standing Committee for Veterinary Medicinal
( 7 ) OJ L 378, 27.12.2006, p. 20.
Products,

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EN
9.6.2012 Official
Journal
of
the
European
Union L
150/69
HAS ADOPTED THIS REGULATION:
evaluation of the risks and benefits of the product, as
provided for in Article 16(2) and Article 41(4) of
Regulation (EC) No 726/2004;
Article 1
Article 1 of Regulation (EC) No 658/2007 is replaced by the
(6) the obligation to keep product information up to
following:
date with current scientific knowledge, including the
conclusions of the assessment and recommendations
‘Article 1
made public on the European medicines web-portal,
as provided for in Article 16(3) of Regulation (EC)
Subject matter and scope
No 726/2004;
This Regulation lays down rules concerning the application
of financial penalties to the holders of marketing authori
(7) the obligation to provide, at the request of the
sations, granted under Regulation (EC) No 726/2004, in
Agency, any data demonstrating that the risk-
respect of infringements of the following obligations, in
benefit balance remains favourable, as provided for
cases where the infringement concerned may have significant
in Article 16(4) and Article 41(4) of Regulation (EC)
public health implications in the Union, or where it has a
No 726/2004;
Union dimension by taking place or having its effects in
more than one Member State, or where interests of the
(8) the obligation to place the medicinal product on the
Union are involved:
market in accordance with the content of the
summary of the product characteristics and the
(1) the obligation to submit complete and accurate
labelling and package leaflet as contained in the
particulars and documents in an application for
marketing authorisation;
marketing authorisation under Regulation (EC) No
726/2004 submitted to the European Medicines
(9) the obligation to comply with the conditions referred
Agency established by that Regulation, (hereinafter
to in Article 14(7) and (8) of Regulation (EC) No
‘the Agency’), or in response to obligations laid
726/2004 or to introduce the specific procedures
down in that Regulation and Regulation (EC) No
referred to in Article 39(7) of Regulation (EC) No
1901/2006 to the extent that the infringement
726/2004;
concerns a material particular;
(10) the obligation to notify the Agency of the dates of
(2) the obligation to comply with conditions or
actual marketing and of the date when the product
restrictions included in the marketing authorisation
ceases to be on the market, and to provide to the
and concerning the supply or use of the medicinal
Agency data relating to the volume of sales and the
product, as referred to in Article 9(4)(b), the second
volume of prescriptions of the product, as provided
subparagraph of Article 10(1), Article 34(4)(c) and
in Article 13(4) and Article 38(4) of Regulation (EC)
the second subparagraph of Article 35(1) of Regu
No 726/2004;
lation (EC) No 726/2004;
(11) the obligation to operate a comprehensive pharmaco
(3) the obligation to comply with conditions or
vigilance system for the fulfilment of pharmaco
restrictions included in the marketing authorisation
vigilance tasks, including the operation of a quality
with regard to the safe and effective use of the
system, maintenance of a pharmacovigilance system
medicinal product as referred to in Article 9(4)(aa),
master file and performance of regular audits, in
(c), (ca), (cb) and (cc), Article 10(1), Article 34(4)(d)
accordance with Article 21 of Regulation (EC) No
and Article 35(1) of Regulation (EC) No 726/2004
726/2004 read together with Article 104 of
taking account of any deadlines set in accordance
Directive 2001/83/EC;
with the third subparagraph of Article 10(1) of Regu
lation (EC) No 726/2004;
(12) the obligation to submit, at the request of the
Agency, a copy of the pharmacovigilance system
(4) the obligation to introduce any necessary variation to
master file, as provided for in Article 16(4) of Regu
the terms of the marketing authorisation to take
lation (EC) No 726/2004;
account of technical and scientific progress and
enable the medicinal products to be manufactured
(13) the obligation to operate a risk management system
and checked by means of generally accepted scientific
as provided for in Article 14a and Article 21(2) of
methods, as provided for in Article 16(1) and
Regulation (EC) No 726/2004 read together with
Article 41(1) of Regulation (EC) No 726/2004;
Article 104(3) of Directive 2001/83/EC and
Article 34(2) of Regulation (EC) No 1901/2006;
(5) the obligation to supply any new information which
may entail a variation to the terms of the marketing
(14) the obligation to record and report suspected adverse
authorisation, to notify any prohibition or restriction
reactions for medicinal products for human use, in
imposed by the competent authorities of any country
accordance with Article 28(1) of Regulation (EC) No
in which the medicinal product is marketed, or to
726/2004 read together with Article 107 of Directive
supply any information that may influence the
2001/83/EC;

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L 150/70
EN
Official Journal of the European Union
9.6.2012
(15) the obligation to submit periodic safety update
misleading and to notify them to the Agency, as
reports, in accordance with Article 28(2) of Regu
provided for in Article 22 of Regulation (EC) No
lation (EC) No 726/2004 read together with
726/2004 read together with Article 106a(1) of
Article 107b of Directive 2001/83/EC;
Directive 2001/83/EC;
(16) the obligation to conduct post-marketing studies,
(24) the obligation to comply with the time limits for
including post-authorisation safety studies and post-
initiating or completing measures specified in the
authorisation efficacy studies, and to submit them for
Agency’s decision on deferral following the initial
review, as provided for in Article 10a of Regulation
marketing authorisation of the medicinal product
(EC) No 726/2004 and Article 34(2) of Regulation
concerned and in accordance with the definitive
(EC) No 1901/2006;
opinion referred to in Article 25(5) of Regulation
(EC) No 1901/2006;
(17) the obligation to record and report all suspected
serious adverse reactions and adverse human
(25) the obligation to place the medicinal product on the
reactions to a veterinary medicinal product as well
market within two years of the date on which the
as all suspected serious unexpected adverse reactions
paediatric indication is authorised, as provided for in
and human adverse reactions or suspected trans
Article 33 of Regulation (EC) No 1901/2006;
mission of infectious agents, as provided for in
Article 49(1) and (2) of Regulation (EC) No
(26) the obligation to transfer the marketing authorisation
726/2004;
or to allow a third party to use documentation
contained in the marketing authorisation dossier, as
(18) the obligation to record in detail all suspected adverse
provided for in the first subparagraph of Article 35
reactions and to submit these records in the form of
of Regulation (EC) No 1901/2006;
periodic safety update reports, as provided for in
Article 49(3) of Regulation (EC) No 726/2004;
(27) the obligation to submit paediatric studies to the
Agency, including the obligation to enter information
(19) the obligation to notify the Agency prior or simulta
into the European database on third country clinical
neously to any communication of information on
trials, as provided for in Article 41(1) and (2),
pharmacovigilance concerns to the general public,
Article 45(1) and Article 46(1) of Regulation (EC)
as provided for in Article 49(5) of Regulation (EC)
No 1901/2006;
No 726/2004;
(20) the obligation to collate and assess specific phar
(28) the obligation to submit an annual report to the
macovigilance data, as provided for in the fourth
Agency as provided for in Article 34(4) of Regulation
paragraph of Article 51 of Regulation (EC) No
(EC) No 1901/2006 and to inform the Agency in
726/2004;
accordance with the second subparagraph of
Article 35 of that Regulation.’.
(21) the obligation to have permanently and continuously
at disposal an appropriately qualified person
Article 2
responsible for pharmacovigilance, as provided for
For infringements that started before 2 July 2012, this Regu
in Article 48 of Regulation (EC) No 726/2004;
lation shall apply to the part of the infringement that takes
place after that date.
(22) the obligation to detect residues in the case of
veterinary medicinal products, as provided for in
Article 3
Article 41(2) and (3) of Regulation (EC) No
726/2004;
This Regulation shall enter into force on the twentieth day
following that of its publication in the Official Journal of the
(23) the obligation to ensure that public announcements
European Union.
relating to information on pharmacovigilance
concerns are presented objectively and are not
It shall apply from 2 July 2012.
This Regulation shall be binding in its entirety and directly applicable in all Member States.
Done at Brussels, 8 June 2012.
For the Commission
The President
José Manuel BARROSO

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