HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN"L 209/4
EN
Official Journal of the European Union
4.8.2012
COMMISSION REGULATION (EU) No 712/2012
of 3 August 2012
amending Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of
marketing authorisations for medicinal products for human use and veterinary medicinal products
(Text with EEA relevance)
THE EUROPEAN COMMISSION,
medicinal products for human use, Regulation (EC) No
726/2004 laying down Community procedures for the
authorisation and supervision of medicinal products for
Having regard to the Treaty on the Functioning of the European
human and veterinary use and establishing a European
Union,
Medicines Agency, and Regulation (EC) No 1394/2007
on advanced therapy medicinal products ( 6 ), and the
provisions of Directive 2010/84/EU of the European
Having regard to Directive 2001/82/EC of the European
Parliament and of the Council of 15 December 2010
Parliament and of the Council of 6 November 2001 on the
amending, as regards pharmacovigilance, Directive
Community code relating to veterinary medicinal products ( 1 ),
2001/83/EC on the Community code relating to
and in particular Article 27b thereof,
medicinal products for human use ( 7 ).
Having regard to Directive 2001/83/EC of the European
(3) For
reasons
of
consistency
and
with
a
view
to
reducing
Parliament and of the Council of 6 November 2001 on the
the administrative burden, variations to purely national
Community code relating to medicinal products for human
marketing authorisations should be processed in
use ( 2 ), and in particular Article 23b(1) thereof,
accordance with the same principles that apply to vari
ations of marketing authorisations granted under the
mutual recognition procedure and the decentralised
Having regard to Regulation (EC) No 726/2004 of the European
procedure. However, the possibilities for grouping vari
Parliament and of the Council of 31 March 2004 laying down
ations should be adapted to the specific characteristics of
Community procedures for the authorisation and supervision of
purely national marketing authorisations.
medicinal products for human and veterinary use and estab
lishing a European Medicines Agency ( 3 ), and in particular
Article 16(4) and Article 41(6) thereof,
(4)
It should be possible to process variations to purely
national marketing authorisations in accordance with
the worksharing procedure under certain conditions.
Whereas:
Where the use of the worksharing procedure has lead
to the harmonisation of a section of the summary of
product characteristics, it should not be possible for the
(1) Directive
2009/53/EC
of
the
European
Parliament
and
of
holder to later undermine the harmonisation achieved by
the Council of 18 June 2009 amending Directive
submitting applications for variations to the section thus
2001/82/EC and Directive 2001/83/EC, as regards vari
harmonised in some of the concerned Member States
ations to the terms of marketing authorisations for
only.
medicinal products
( 4 ), requires the Commission to
adopt appropriate arrangements for the examination of
variations to the terms of marketing authorisations
(5) Grouping
of
several
variations
in
a
single
submission
is
granted in accordance with Directives 2001/82/EC and
possible in some cases. It should be clarified that, where
2001/83/EC not yet covered by Commission Regulation
several variations are grouped, the procedure for the
(EC) No 1234/2008 ( 5 ). It is therefore appropriate to
handling of the variations in the group and the rules
extend the scope of Regulation (EC) No 1234/2008.
for the implementation of those variations should be
The variations of all marketing authorisations granted
those of the variation of the highest grade. In order to
in the EU in accordance with the acquis should be
facilitate the acceptance of complex groupings by the
subject to the procedures laid down in Regulation (EC)
relevant authorities, it should be possible to extend the
No 1234/2008.
assessment period.
(2) The
definition
of
variation
should
be
clarified
and
updated in particular to take into consideration the
(6) The
worksharing
procedure
is
intended
to
avoid
dupli
provisions of Regulation (EU) No 1235/2010 of the
cation of work. Accordingly, it should be possible for
European Parliament and of the Council of 15 December
competent authorities to process under the same
2010 amending, as regards pharmacovigilance of
procedure variations to purely national marketing auth
orisations, variations to marketing authorisations granted
under the mutual recognition or decentralised procedure,
( 1 ) OJ L 311, 28.11.2001, p. 1.
and variations to centralised marketing authorisations.
( 2 ) OJ L 311, 28.11.2001, p. 67.
( 3 ) OJ L 136, 30.4.2004, p. 1.
( 4 ) OJ L 168, 30.6.2009, p. 33.
( 6 ) OJ L 348, 31.12.2010, p. 1.
( 5 ) OJ L 334, 12.12.2008, p. 7.
( 7 ) OJ L 348, 31.12.2010, p. 74.

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(7) The
procedure
for
the
variation
of
human
influenza
‘1. This Regulation lays down provisions
vaccines should be streamlined. Competent authorities
concerning the examination of variations to the
should still be able to start the assessment in the
terms of all marketing authorisations for medicinal
absence of clinical and stability data and take a
products for human use and veterinary medicinal
decision if no additional information is considered
products granted in accordance with Regulation (EC)
necessary. However, if clinical and stability data is
No 726/2004, Directive 2001/83/EC, Directive
requested, the competent authorities should not be
2001/82/EC, and Council Directive 87/22/EEC (*).
required to take a decision until the assessment thereof
has been finalised.
___________
(*) OJ L 15, 17.1.1987, p. 38.’;
(8) For
medicinal
products
authorised
under
Regulation
(EC)
No 726/2004, the refusal of the European Medicines
Agency to accept a variation should terminate the
(b) the following paragraph shall be inserted after
procedure. Likewise, a Commission decision should not
paragraph (3):
be required regarding variations that do not amend the
terms of the decision granting the marketing authori
‘3a. Chapter IIa shall apply only to variations to the
sation.
terms of purely national marketing authorisations.’;
(9) The
European
Medicines
Agency
has
the
expertise
to
(2) Article 2 is amended as follows:
assess the need for urgent safety restrictions regarding
medicinal products authorised under the centralised
(a) paragraph 1 is replaced by the following:
procedure. Marketing authorisation holders of medicinal
products authorised under Regulation (EC) No 726/2004
should therefore inform the Agency if they consider that
‘1. “Variation
to
the
terms
of
a
marketing
authori
urgent safety measures are necessary.
sation” or “variation” means any amendment to:

(a) the information referred to in Articles 12(3) to 14
(10) A proliferation of variation procedures leading to
of Directive 2001/82/EC and Annex I thereto,
frequent changes in the terms of the decision granting
Articles 8(3) to 11 of Directive 2001/83/EC and
the marketing authorisation for centralised marketing
Annex I thereto, Articles 6(2) and 31(2) of Regu
authorisations has been identified. Changes that are
lation (EC) No 726/2004, or Article 7 of Regu
critical for public health should be reflected in the
lation (EC) No 1394/2007;
decision granting the marketing authorisation promptly.
However, other changes should be reflected in the
(b) the terms of the decision granting the marketing
decision granting the marketing authorisation according
authorisation for a medicinal product for human
to timelines that ensure reasonable periodic updates of
use, including the summary of the product char
the decision granting the marketing authorisations while
acteristics and any conditions, obligations, or
facilitating the identification of variations with the
restrictions affecting the marketing authorisation,
greatest impact on public health.
or changes to the labelling or the package leaflet
connected with changes to the summary of the
(11) The
principles
governing
the
implementation
of
vari
product characteristics;
ations should be adjusted while keeping the principle
that it should be possible for the marketing authorisation
(c) the terms of the decision granting the marketing
holder to implement certain variations prior to the
authorisation for a veterinary medicinal product,
relevant marketing authorisation being changed.
including the summary of the product character
istics and any conditions, obligations, or
restrictions affecting the marketing authorisation,
(12) The
measures
provided
for
in
this
Regulation
are
in
accordance with the opinion of the Standing
or changes to the labelling or the package leaflet.’;
Committee on Medicinal Products for Human Use and
the Standing Committee on Veterinary Medicinal
(b) paragraph 8 is replaced by the following:
Products,
‘8. “Urgent
safety
restriction”
means
an
interim
change in the terms of the marketing authorisation
HAS ADOPTED THIS REGULATION:
due to new information having a bearing on the safe
use of the medicinal product.’;
Article 1
Amendments to Regulation (EC) No 1234/2008
(c) the following paragraph 9 is added:
Regulation (EC) No 1234/2008 is amended as follows:
‘9. “Purely
national
marketing
authorisation”
means
any marketing authorisation granted by a Member
(1) Article 1 is amended as follows:
State in accordance with the acquis outside the
mutual recognition or decentralised procedure and
that has not been subject to a complete harmonisation
(a) paragraph 1 is replaced by the following:
following a referral procedure.’;

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Official Journal of the European Union
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(3) Article 3 is amended as follows:
The recommendation referred to in the first
subparagraph shall be consistent with the guidelines
(a) paragraph 2 is replaced by the following:
referred to in Article 4(1). It shall be delivered within
45 days following receipt of the request and sent to
‘2. A
variation
which
is
not
an
extension
and
whose
the holder, the Agency, and the coordination group
classification is undetermined after application of the
referred to in Article 31 of Directive 2001/82/EC or
rules provided for in this Regulation, taking into
in Article 27 of Directive 2001/83/EC.
account the guidelines referred to in Article 4(1) and,
where relevant, any recommendations delivered
The 45-day period referred to in the second
pursuant to Article 5, shall by default be considered
subparagraph may be extended by 25 days where
a minor variation of type IB.’;
the relevant authority deems it necessary to consult
with the coordination group.’;
(b) in paragraph 3, point (b) is replaced by the following:
‘(b) where the competent authority of the reference
(b)
the following paragraph 1a is inserted after
Member State as referred to in Article 32 of
paragraph 1:
Directive 2001/82/EC and Article 28 of Directive
2001/83/EC (hereinafter “the reference Member
State”), in consultation with the other Member
‘1a. Prior
to
the
examination
of
a
variation
whose
States concerned, or the Agency in the case of a
classification is not provided for in this Regulation, a
centralised marketing authorisation, or the
competent authority of a Member State may request a
competent authority in the case of a purely
recommendation on the classification of the variation
national marketing authorisation, concludes,
to the coordination group.
following the assessment of validity of a notifi
cation in accordance with Article 9(1),
The recommendation referred to in the first
Article 13b(1), or Article 15(1) and taking into
subparagraph shall be consistent with the guidelines
account the recommendations delivered pursuant
referred to in Article 4(1). It shall be delivered within
to Article 5, that the variation may have a
45 days following receipt of the request and sent to
significant impact on the quality, safety or
the holder, the Agency, and the competent authorities
efficacy of the medicinal product concerned.’;
of all Member States.’;
(4) Article 4 is replaced by the following:
(6) Article 7 is replaced by the following:
‘Article 4
Guidelines
‘Article 7
1. The
Commission
shall,
after
consulting
the
Member
Grouping of variations
States and the Agency, draw up guidelines on the details of
1. Where
several
variations
are
notified
or
applied
for,
a
the various categories of variations, on the operation of
separate notification or application in accordance with
the procedures laid down in Chapters II, IIa, III and IV of
Chapters II, III, or Article 19 as appropriate shall be
this Regulation, and on the documentation to be
submitted in respect of each variation sought.
submitted pursuant to those procedures.
2. The
guidelines
referred
to
in
paragraph
1
shall
be
2. By
way
of
derogation
from
paragraph
1,
the
regularly updated.’;
following shall apply:
(5) Article 5 is amended as follows:
(a) where the same minor variation(s) of type IA to the
terms of one or more marketing authorisations owned
(a) paragraph 1 is replaced by the following:
by the same holder are notified at the same time to the
same relevant authority, a single notification as
‘1. Prior
to
the
submission
of
a
variation
whose
referred to in Article 8 or 14 may cover all such
classification is not provided for in this Regulation, a
variations;
holder may request a recommendation on the classifi
cation of the variation as follows:
(b) where several variations to the terms of the same
(a) to the Agency, where the variation refers to a
marketing authorisation are submitted at the same
marketing authorisation granted under Regulation
time, a single submission may cover all such variations
(EC) No 726/2004;
provided that the variations concerned fall within one
of the cases listed in Annex III;
(b) to the competent authority of the Member State
concerned, where the variation refers to a purely
(c) where several variations to the terms of the same
national marketing authorisation;
marketing authorisation are submitted at the same
time and the variations do not fall within one of the
(c) to the competent authority of the reference
cases listed in Annex III, a single submission may
Member State, in the other cases.
cover all such variations provided that the competent

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authority of the reference Member State in consul
‘3. The competent authority of the reference
tation with the competent authorities of the Member
Member State shall assess the application submitted.
States concerned or, in the case of a centralised
Where deemed necessary, the competent authority of
marketing authorisation, the Agency agrees to such
the reference Member State may request additional
single submission.
data to the holder in order to complete its assessment.
The submission referred to in subparagraphs (b) and (c)
4. The
competent
authority
shall
prepare
a
decision
shall be made simultaneously to all relevant authorities by
and an assessment report within 45 days from the
means of the following:
receipt of a valid application.
(i) a single notification in accordance with Article 9 or
The 45-day period referred to in the first subparagraph
15 where at least one of the variations is a minor
shall be suspended from the moment when the
variation of type IB and the remaining variations are
additional data referred to in paragraph 3 is
minor variations;
requested until the data is submitted.
(ii) a single application in accordance with Article 10 or
5. Within 12 days from the receipt of the decision
16 where at least one of the variations is a major
and the assessment report of the competent authority
variation of type II and none of the variations is an
of the reference Member State, the relevant authorities
extension;
shall adopt a decision accordingly and inform the
competent authority of the reference Member State
(iii) a single application in accordance with Article 19
and the holder thereof.’;
where at least one of the variations is an extension.’;
(c) paragraph 6 is deleted;
(7) in Article 9, the following paragraph 5 is added:
(10) the following Chapter IIa is inserted after Article 13:
‘5. This
Article
shall
not
apply
where
a
type
IB
variation
request is submitted in a grouping that includes a variation
type II and does not contain an extension. In such case,
‘CHAPTER IIa
the prior approval procedure in Article 10 shall apply.
VARIATIONS TO PURELY NATIONAL MARKETING
AUTHORISATIONS
This Article shall not apply where a type IB variation
request is submitted in a grouping that includes an
Article 13a
extension. In such case, the procedure in Article 19 shall
Notification procedure for minor variations of
apply.’;
type IA
(8) Article 10 is amended as follows:
1. Where
a
minor
variation
of
type
IA
is
made,
the
holder shall submit to the competent authority a notifi
(a) in paragraph 2, the second subparagraph is replaced by
cation containing the elements listed in Annex IV. This
the following:
notification shall be submitted within 12 months
following the implementation of the variation.
‘The competent authority of the reference Member
State may reduce the period referred to in the first
However, the notification shall be submitted immediately
subparagraph, having regard to the urgency of the
after the implementation of the variation in the case of
matter, or extend it to 90 days for variations listed
minor variations requiring immediate notification for the
in Part 1 of Annex V or for grouping of variations
continuous supervision of the medicinal product
in accordance with Article 7(2)(c).’;
concerned.
(b) the following paragraph 6 is added:
2. Within
30
days
following
receipt
of
the
notification,
the measures provided for in Article 13e shall be taken.
‘6. This
Article
shall
not
apply
where
a
type
II
variation request is submitted in a grouping that
Article 13b
includes an extension. In such case, the procedure in
Notification procedure for minor variations of type IB
Article 19 shall apply.’;
1. The
holder
shall
submit
to
the
competent
authority
a
(9) Article 12 is amended as follows:
notification containing the elements listed in Annex IV.
(a) paragraph 1 is replaced by the following:
If the notification fulfils the requirement laid down in the
first subparagraph, the competent authority shall
‘1. By way of derogation from Article 10, the
acknowledge receipt of a valid notification.
procedure laid down in paragraphs 2 to 5 shall
apply to the examination of variations concerning
2. If
within
30
days
following
the
acknowledgement
of
changes to the active substance for the purposes of
receipt of a valid notification, the competent authority has
the annual update of a human influenza vaccine.’;
not sent the holder an unfavourable opinion, the notifi
cation shall be deemed accepted by the competent auth
(b) paragraphs 3, 4 and 5 are replaced by the following:
ority.

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Where the notification is accepted by the competent auth
4. Within 30 days
after
the
conclusion
of the
ority, the measures provided for in Article 13e shall be
assessment, the measures provided for in Article 13e
taken.
shall be taken.
3. Where the competent authority is of the opinion
5. This
Article
shall
not
apply
where
a
type
II
variation
that the notification cannot be accepted, it shall inform
request is submitted in a grouping that includes an
the holder, stating the grounds on which its unfavourable
extension. In such case, the procedure in Article 19 shall
opinion is based.
apply.
Within 30 days following the receipt of the unfavourable
Article 13d
opinion, the holder may submit to the competent
Grouping of variations to purely national marketing
authority an amended notification in order to take due
authorisations
account of the grounds laid down in that opinion.
1. Where
several
variations
are
notified
or
applied
for,
a
If the holder does not amend the notification in
separate notification or application in accordance with
accordance with the second subparagraph, the notification
Articles 13a, 13b, 13c, or 19 as appropriate shall be
shall be deemed rejected.
submitted to the competent authority in respect of each
variation sought.
4. Where
an
amended
notification
has
been
submitted,
the competent authority shall assess it within 30 days
2. By
way
of
derogation
from
paragraph
1
the
following its receipt and the measures provided for in
following shall apply:
Article 13e shall be taken.
(a) where the same minor variation(s) of type IA to the
5. This
Article
shall
not
apply
where
a
type
IB
variation
terms of one or more marketing authorisations owned
request is submitted in a grouping that includes a variation
by the same holder are notified at the same time to the
type II and does not contain an extension. In such case,
same competent authority, a single notification as
the prior approval procedure in Article 13c shall apply.
referred to in Article 13a may cover all such variations;
This Article shall not apply where a type IB variation
(b) where several variations to the terms of the same
request is submitted in a grouping that includes an
marketing authorisation are submitted at the same
extension. In such case, the procedure in Article 19 shall
time to the same competent authority, a single
apply.
submission may cover all such variations provided
that the variations concerned fall within one of the
cases listed in Annex III;
Article 13c
“Prior Approval” procedure for major variations of
(c) where the same variation(s) to the terms of one or
type II
more marketing authorisations owned by the same
holder are submitted at the same time to the same
1. The
holder
shall
submit
to
the
competent
authority
competent authority and they are not covered under
an application containing the elements listed in Annex IV.
subparagraph (a) or (b), a single submission may cover
all such variations provided that the competent
If the application fulfils the requirements laid down in the
authority agrees to such single submission.
first subparagraph, the competent authority shall
acknowledge receipt of a valid application.
The submission referred to in points (b) and (c) shall be
made by means of the following:
2. Within
60
days
following
the
acknowledgement
of
receipt of a valid application, the competent authority shall
(i) a single notification in accordance with Article 13b
conclude the assessment.
where at least one of the variations is a minor
variation of type IB and the remaining variations are
The competent authority may reduce the period referred to
minor variations;
in the first subparagraph, having regard to the urgency of
the matter, or extend it to 90 days for variations listed in
(ii) a single application in accordance with Article 13c
Part 1 of Annex V or for grouping of variations in
where at least one of the variations is a major
accordance with Article 13d(2)(c).
variation of type II and none of the variations is an
extension;
The period referred to in the first subparagraph shall be 90
days for variations listed in Part 2 of Annex V.
(iii) a single application in accordance with Article 19
where at least one of the variations is an extension.
3. Within
the
periods
referred
to
in
paragraph
2,
the
competent authority may request the holder to provide
Article 13e
supplementary information within a time limit set by the
Measures to close the procedures of Articles 13a to
competent authority. In this case the procedure shall be
13c
suspended until such supplementary information has been
provided and the competent authority may extend the
Where reference is made to this Article, the competent
period referred to in paragraph 2.
authority shall take the following measures:

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(a) it shall inform the holder as to whether the variation is
(a) in paragraph 2, the second subparagraph is replaced by
accepted or rejected;
the following:
(b) where the variation is rejected, it shall inform the
‘The Agency may reduce the period referred to in the
holder of the grounds for the rejection;
first subparagraph, having regard to the urgency of the
matter, or extend it to 90 days for variations listed in
(c) where necessary, it shall amend the decision granting
Part 1 of Annex V or for grouping of variations in
the marketing authorisation in accordance with the
accordance with Article 7(2)(c).’;
accepted variation within the time limit laid down in
paragraph 1 of Article 23.
(b) the following paragraph 5 is added:
Article 13f
‘5. This
Article
shall
not
apply
where
a
type
II
Human influenza vaccines
variation request is submitted in a grouping that
includes an extension. In such case, the procedure in
1. By
way
of
derogation
from
Article
13c,
the
Article 19 shall apply.’;
procedure laid down in paragraphs 2 to 4 shall apply to
the examination of variations concerning changes to the
(13) Article 17 is replaced by the following:
active substance for the purposes of the annual update of a
human influenza vaccine.
‘Article 17
2. The
holder
shall
submit
to
the
competent
authority
Measures to close the procedures of Articles 14 to 16
an application containing the elements listed in Annex IV.
1. Where reference is made to this Article, the Agency
shall take the following measures:
If the application fulfils the requirements laid down in the
first subparagraph, the competent authority shall
acknowledge receipt of a valid application.
(a) it shall inform the holder of the outcome of the
assessment;
3. The
competent
authority
shall
assess
the
application
submitted. Where deemed necessary, the competent
(b) where the variation is rejected, it shall inform the
authority may request additional data to the holder in
holder of the grounds for the rejection;
order to complete its assessment.
(c) where the outcome of the assessment is favourable and
4. The
competent
authority
shall
adopt
a
decision
the variation affects the terms of the Commission
within 45 days from the receipt of a valid application
decision granting the marketing authorisation, the
and shall take the measures provided for in Article 13e.
Agency shall transmit to the Commission its opinion
and the grounds for its opinion as well as the revised
The 45-day period referred to in the first subparagraph
versions of the documents referred to in Article 9(4) or
shall be suspended from the moment when the additional
Article 34(4) of Regulation (EC) No 726/2004 as
data referred to in paragraph 3 is requested until the data
appropriate.
is submitted.’;
2. In
the
cases
identified
under
paragraph
1(c),
the
(11) Article 15 is amended as follows:
Commission, having regard to the opinion from the
Agency and within the time limit foreseen in
(a) in paragraph 3, the third subparagraph is replaced by
Article 23(1a), shall amend where necessary the decision
the following:
granting the marketing authorisation. The Community
Register of Medicinal Products provided for in Article 13(1)
and Article 38(1) of Regulation (EC) No 726/2004 shall be
‘If the holder does not amend the notification in
updated accordingly.’;
accordance with the second subparagraph, the notifi
cation shall be deemed rejected.’;
(14) Article 18 is amended as follows:
(b) the following paragraph 5 is added:
(a) paragraph 1 is replaced by the following:
‘5. This
Article
shall
not
apply
where
a
type
IB
variation request is submitted in a grouping that
‘1. By way of derogation from Article 16, the
includes a variation type II and does not contain an
procedure laid down in paragraphs 2 to 6 shall
extension. In such case, the prior approval procedure
apply to the examination of variations concerning
in Article 16 shall apply.
changes to the active substance for the purposes of
the annual update of a human influenza vaccine.’;
This Article shall not apply where a type IB variation
request is submitted in a grouping that includes an
(b) paragraphs 3, 4, 5 and 6 are replaced by the following:
extension. In such case, the procedure in Article 19
shall apply.’;
‘3. The Agency shall assess the application
submitted. Where deemed necessary, the Agency may
(12) Article 16 is amended as follows:
request additional data to complete its assessment.

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4. Within
55
days
from
the
receipt
of
a
valid
appli
Variations covered under (a), (b) or (c) may be subject
cation, the Agency shall adopt an opinion. The
to the same worksharing procedure.
Agency’s opinion on the application shall be trans
mitted to the applicant. Where the Agency’s opinion
is favourable, the Agency shall also transmit to the
The reference authority or, in the case of purely
Commission its opinion and the grounds for its
national marketing authorisations, the competent
opinion as well as the revised versions of the
authority may refuse to process a submission under
documents referred in Article 9(4) of Regulation (EC)
the worksharing procedure where the same change(s)
No 726/2004.
to different marketing authorisations require the
submission of individual supportive data for each
medicinal product concerned or a separate product-
5. The
55-day
period
referred
to
in
paragraph
4
specific assessment.’;
shall be suspended from the moment when the
additional data referred to in paragraph 3 is
(b) paragraph 2 is replaced by the following:
requested until the data is submitted.
‘2. For
the
purposes
of
this
Article,
“reference
auth
6. Having
regard
to
the
favourable
opinion
of
the
ority” shall mean one of the following:
Agency, the Commission shall amend where necessary
the decision granting the marketing authorisation. The
(a) the Agency where at least one of the marketing
Community Register of Medicinal Products provided
authorisations referred to paragraph 1 is a
for in Article 13(1) of Regulation (EC) No 726/2004
centralised marketing authorisation;
shall be updated accordingly.’;
(b) the competent authority of a Member State
(c) paragraph 7 is deleted;
concerned chosen by the coordination group,
taking into account a recommendation of the
holder, in the other cases.’;
(15) Article 20 is amended as follows:
(c) in paragraph 3, the first and second subparagraphs are
replaced by the following:
(a) paragraph 1 is replaced by the following:
‘3. The
holder
shall
submit
to
all
relevant
auth
‘1. By way of derogation from Articles 7(1), 9, 10,
orities an application containing the elements listed
13b, 13c, 13d, 15 and 16 the holder of a marketing
in Annex IV, with an indication of the preferred
authorisation may choose to follow the worksharing
reference authority.
procedure laid down in paragraphs 3 to 9 in the
following cases:
The coordination group shall choose a reference auth
ority. If the application fulfils the requirements laid
down in the first subparagraph, that reference
(a) for marketing authorisations referred to in
authority shall acknowledge receipt of a valid appli
Chapters II and III, where a minor variation of
cation.’;
type IB, a major variation of type II, or a group
of variations as provided for in Article 7(2)(b) or
(c) that does not contain any extension relates to
(d) paragraphs 4 and 5 are replaced by the following:
several marketing authorisations owned by the
same holder;
‘4. The
reference
authority
shall
issue
an
opinion
on
a valid application as referred to in paragraph 3 within
one of the following periods:
(b) for purely national marketing authorisations
referred to in Chapter IIa, where a minor
variation of type IB, a major variation of type II,
(a) a period of 60 days following acknowledgement of
or a group of variations as provided for in
receipt of a valid application in the case of minor
Article 13d(2)(b) or (c) that does not contain any
variations of type IB or major variations of type II;
extension relates to several marketing authori
sations owned by the same holder;
(b) a period of 90 days following acknowledgement of
receipt of a valid application in the case of vari
(c) for purely national marketing authorisations
ations listed in Part 2 of Annex V.
referred to in Chapter IIa, where a minor
variation of type IB, a major variation of type II,
5. The
reference
authority
may
reduce
the
period
or a group of variations as provided for in
referred to in point (a) of paragraph 4, having regard
Article 13d(2)(b) or (c) that does not contain any
to the urgency of the matter, or extend it to 90 days
extension relates to one marketing authorisation
for variations listed in Part 1 of Annex V or for
that is owned by the same holder in more than
grouping of variations in accordance with
one Member State.
Article 7(2)(c) or Article 13d(2)(c).’;

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EN
4.8.2012 Official
Journal
of
the
European
Union L
209/11
(e) paragraphs 7 and 8 are replaced by the following:
‘10. Where
harmonisation
of
a
section
of
the
summary of product characteristics of a purely
‘7. Where the reference authority is the Agency,
national marketing authorisation has been achieved
Article 9(1) and (2) and Article 34(1) and (2) of Regu
through a worksharing procedure, any subsequent
lation (EC) No 726/2004 shall apply to the opinion
variation submission affecting the harmonised section
referred to in paragraph 4.
shall be transmitted simultaneously to all Member
States concerned.’;
The Agency’s opinion on the application shall be
transmitted to the applicant and the Member States,
(16) in Article 21, paragraph 1 is replaced by the following:
together with the assessment report. Where the
outcome of the assessment is favourable and the
‘1. By
way
of
derogation
from
Chapters
I,
II,
IIa
and
III,
variation affects the terms of the Commission
where a pandemic situation with respect to human
decision granting the marketing authorisation, the
influenza is duly recognised by the World Health Organi
Agency shall also transmit to the Commission its
sation or by the Union in the framework of Decision
opinion and the grounds for its opinion as well as
2119/98/EC of the European Parliament and of the Coun
the revised versions of the documents referred in
cil (*), the relevant authorities or, in the case of centralised
Article 9(4) of Regulation (EC) No 726/2004.
marketing authorisations, the Commission may excep
tionally and temporarily accept a variation to the terms
Where the Agency issues a favourable opinion, the
of a marketing authorisation for a human influenza
following shall apply:
vaccine, where certain non-clinical or clinical data are
missing.
(a) if the opinion recommends the variation to the
terms of a Commission decision granting the
___________
marketing authorisation, the Commission shall,
(*) OJ L 268, 3.10.1998, p. 1.’;
having regard to the final opinion and within the
time limits foreseen in Article 23(1a), amend the
decision(s) accordingly, provided that the revised
(17) in Article 22, paragraph 1 is replaced by the following:
versions of the documents referred to in
Article 9(4) or Article 34(4) of Regulation (EC)
No 726/2004 have been received. The
‘1. Where, in the event of a risk to public health in the
Community Register of Medicinal Products
case of medicinal products for human use or, in the case
provided for in Article 13(1) and Article 38(1) of
of veterinary medicinal products, in the event of a risk to
Regulation (EC) No 726/2004 shall be updated
human or animal health or to the environment, the holder
accordingly;
takes urgent safety restrictions on its own initiative, it shall
forthwith inform all relevant authorities and, in the case of
a centralised marketing authorisation, the Agency.
(b) the Member States concerned shall, within 60 days
following receipt of the final opinion of the
Agency, approve that final opinion, inform the
If the relevant authority or, in the case of a centralised
Agency thereof and, where necessary, amend the
marketing authorisation, the Agency has not raised
marketing authorisations concerned accordingly,
objections within 24 hours following receipt of that
provided that the documents necessary for the
information, the urgent safety restrictions shall be
amendment of the marketing authorisation have
deemed accepted.’;
been transmitted to the Member States concerned.
(18) Article 23 is amended as follows:
8. Where the reference authority is the competent
authority of a Member State:
(a) paragraph 1 is replaced by the following:
(a) it shall send its opinion to the holder and to all
‘1. Amendments
to
the
decision
granting
the
relevant authorities;
marketing authorisation resulting from the procedures
laid down in Chapters II and IIa shall be made:
(b) without prejudice to Article 13 and within 30 days
following receipt of the opinion, the relevant auth
(a) in the case of major variations of type II, within
orities shall approve that opinion and inform the
two months following receipt of the information
reference authority;
referred to in Article 11(1)(c) and Article 13e(a),
provided that the documents necessary for the
(c) the concerned marketing authorisations shall be
amendment of the marketing authorisation have
amended accordingly within 30 days following
been transmitted to the Member States concerned;
the approval of the opinion, provided that the
documents necessary for the amendment of the
(b) in the other cases, within six months following
marketing authorisation have been transmitted to
receipt of the information referred to in
the Member States concerned.’;
Article 11(1)(c) and Article 13e(a), provided that
the documents necessary for the amendment of
(f) the following paragraph 10 is inserted after
the marketing authorisation have been transmitted
paragraph 9:
to the Member States concerned.’;

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L 209/12
EN
Official Journal of the European Union
4.8.2012
(b)
the following paragraph 1a is inserted after
under Article 28(3) of Regulation (EC) No 1901/2006
paragraph 1:
shall be included within the technical dossier of the
marketing authorisation.
‘1a. Amendments
to
the
decision
granting
the
marketing authorisation resulting from the procedures
laid down in Chapter III shall be made:
The relevant authority shall provide the holder with a
confirmation that the statement is included in the
(a) within two months following receipt of the
technical dossier within 30 days after the relevant
information referred to in Article 17(1)(c) for the
assessment has been concluded.’;
following variations:
(20) Article 24 is replaced by the following:
(i) variations related to the addition of a new
therapeutic indication or to the modification
of an existing one;
‘Article 24
Implementation of variations
(ii) variations related to the addition of a new
contraindication;
1. Minor
variations
of
type
IA
may
be
implemented
any
time before completion of the procedures laid down in
(iii) variations related to a change in posology;
Articles 8, 13a and 14.
(iv) variations related to the addition of a non-
food producing target species or the modifi
Where a notification concerning one or several minor
cation of an existing one for veterinary
variations of type IA is rejected, the holder shall cease to
medicinal products;
apply the concerned variation(s) immediately after receipt
of the information referred to in Articles 11(1)(a), 13e(a),
(v) variations concerning the replacement or
and 17(1)(a).
addition of a serotype, strain, antigen or
combination of serotypes, strains or
2. Minor
variations
of
type
IB
may
only
be
imple
antigens for a veterinary vaccine;
mented in the following cases:
(vi) variations related to changes to the active
substance of a seasonal, pre-pandemic or
(a) for variations submitted in accordance with the
pandemic vaccine against human influenza;
procedures laid down in Chapter II, after the
competent authority of the reference Member State
(vii) variations related to changes to the with
has informed the holder that it has accepted the notifi
drawal period for a veterinary medicinal
cation pursuant to Article 9, or after the notification is
product;
deemed accepted pursuant to Article 9(2);
(viii) other type II variations that are intended to
(b) for variations submitted in accordance with the
implement changes to the decision granting
procedures laid down in Chapter IIa, after the
the marketing authorisation due to a
relevant authority has informed the holder that it has
significant public health concern or
accepted the notification pursuant to Article 13b, or
significant animal health or environmental
after the notification is deemed accepted pursuant to
concern in the case of veterinary medicinal
Article 13b(2);
products;
(b) within 12 months following receipt of the
(c) for variations submitted in accordance with the
information referred to in Article 17(1)(c) in the
procedures laid down in Chapter III, after the Agency
other cases.
has informed the holder that its opinion referred to in
Article 15 is favourable, or after that opinion is
The Agency shall determine the variations referred
deemed favourable pursuant to Article 15(2);
to in point (a)(viii) and provide reasons for such
determination.’;
(d) for variations submitted in accordance with the
procedure laid down in Article 20, after the
(c) paragraph 2 is replaced by the following:
reference authority has informed the holder that its
‘2. Where
the
decision
granting
a
marketing
auth
opinion is favourable.
orisation is amended as a result of one of the
procedures laid down in Chapters II, IIa, III and IV,
3. Major
variations
of
type
II
may
only
be
implemented
the relevant authority or, in the case of centralised
in the following cases:
marketing authorisations, the Commission shall
notify the amended decision without delay to the
(a) for variations submitted in accordance with the
holder.’;
procedures laid down in Chapter II, 30 days after the
competent authority of the reference Member State has
(19) the following Article 23a is inserted after Article 23:
informed the holder that it has accepted the variation
‘Article 23a
pursuant to Article 10, under the condition that the
documents necessary for the amendment to the
The statement indicating compliance with the agreed
marketing authorisation have been provided to the
completed paediatric investigation plan provided for
Member States concerned. Where an arbitration

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EN
4.8.2012 Official
Journal
of
the
European
Union L
209/13
procedure has been initiated in accordance with
time frame agreed by the holder and the relevant authority
Article 13, the holder shall not implement the
and, in the case of a centralised marketing authorisation,
variation until the arbitration procedure has
the Agency.
concluded that the variation is accepted;
By way of derogation from the first subparagraph, urgent
safety restrictions and variations related to safety issues
(b) for variations submitted in accordance with the
which concern marketing authorisations granted in
procedures laid down in Chapter IIa, after the
accordance with Chapter 4 of Directive 2001/82/EC or
competent authority has informed the holder that it
Chapter 4 of Directive 2001/83/EC shall be implemented
has accepted the variation pursuant to Article 13c;
within a time frame agreed by the holder and the
competent authority of the reference Member State, in
consultation with the other relevant authorities.’;
(c) for variations submitted in accordance with the
procedures laid down in Chapter III, after the Agency
(21) the title of Annex III is replaced by the following:
has informed the holder that its opinion referred to in
Article 16 is favourable, unless the variation is one
‘Cases for grouping variations referred to in
referred to in Article 23(1a)(a).
Article 7(2)(b) and Article 13d(2)(b)’;
(22) the following Article 24a is inserted after Article 24:
Variations referred to in Article 23(1a)(a) may only be
implemented after the Commission has amended the
‘Article 24a
decision granting the marketing authorisation and
notified the holder thereof;
Application of national provisions on variations to
purely national marketing authorisations
Member States that, in accordance with Article 23b(4) of
Directive 2001/83/EC, may continue to apply their
(d) for variations submitted in accordance with the
national provisions on variations to certain purely
procedure laid down in Article 20, 30 days after the
national marketing authorisations are listed in Annex VI
reference authority has informed the holder that its
to this Regulation.’;
opinion is favourable, under the condition that the
documents necessary for the amendment to the
marketing authorisation have been provided to the
(23) the Annex set out in the Annex to this Regulation is
Member States concerned; unless an arbitration
added.
procedure has been initiated in accordance with
Article 13, or unless the procedure concerns a
variation to a centralised marketing authorisation as
Article 2
referred to in Article 23(1a)(a).
Transitional arrangements
From 2 November 2012, the following changes shall apply:
Where an arbitration procedure has been initiated in
accordance with Article 13, or where the worksharing
(a) in Article 23(1) of Regulation (EC) No 1234/2008, the
procedure concerns a variation to a centralised
reference to ‘Chapters II and III’ is replaced by ‘Chapter II’;
marketing authorisation as referred to in
Article 23(1a)(a), the holder shall not implement the
variation until the arbitration procedure has concluded
(b) in Article 23(1) of Regulation (EC) No 1234/2008,
that the variation is accepted, or until the Commission
subparagraph (a) is deleted.
Decision amending the decision granting the
marketing authorisation has been adopted.
Article 3
Entry into force and application
4. An
extension
may
only
be
implemented
after
the 1. This Regulation shall enter into force on the twentieth day
relevant authority or, in the case of extensions to a
following that of its publication in the Official Journal of the
centralised marketing authorisation, the Commission has
European Union.
amended the decision granting the marketing authorisation
and notified the holder accordingly.
2. It
shall
apply
from
2
November
2012.
5. Urgent
safety
restrictions
and
variations
which
are However, points (10), (15), (18)(a) and (c), (21), (22) and (23) of
related to safety issues shall be implemented within a
Article 1 shall apply from 4 August 2013.

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L 209/14
EN
Official Journal of the European Union
4.8.2012
This Regulation shall be binding in its entirety and directly applicable in all Member States.
Done at Brussels, 3 August 2012.
For the Commission
The President
José Manuel BARROSO
ANNEX
‘ANNEX VI
List of Member States referred in Article 24a
the Republic of Bulgaria,
the Federal Republic of Germany.’

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Document Outline

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