EN    EN  
 EUROPEAN COMMISSION 
Brussels, XXX   
[…](2012) XXX  draft 
  
COMMISSION REGULATION (EU) No …/.. 
of XXX  
amending Commission Regulation (EC) No 1234/2008 concerning the examination of 
variations to the terms of ma rketing authorisations for medicinal products for human 
use and veterinary medicinal products 
(Text with EEA relevance) 
  
EN 2   EN COMMISSION REGULATION (EU) No …/.. 
of XXX 
amending Commission Regulation (EC) No  1234/2008 concerning the examination of 
variations to the terms of marketing author isations for medicinal products for human 
use and veterinary medicinal products 
(Text with EEA relevance) 
THE EUROPEAN COMMISSION, 
Having regard to the Treaty on the Functioning of the European Union, Having regard to Directive 2001/82/EC of the Eu ropean Parliament and of the Council of 6 
November 2001 on the Community code rela ting to veterinary medicinal products
1, and in 
particular Article 27b thereof, 
Having regard to Directive 2001/83/EC of the Eu ropean Parliament and of the Council of 6 
November 2001 on the Community code relati ng to medicinal products for human use2, and 
in particular Article 23b(1) thereof,  
Having regard to Regulation (EC) No 726/2004 of the European Parliament and of the 
Council of 31 March 2004 laying down Community procedures for the authorisation and 
supervision of medicinal products for human a nd veterinary use and establishing a European 
Medicines Agency3, and in particular Article 16( 4) and Article 41(6) thereof, 
Whereas: (1) Directive 2009/53/EC of the Eu ropean Parliament and of the Council of 18 June 2009 
amending Directive 2001/82/EC and Directiv e 2001/83/EC, as regards variations to 
the terms of marketing aut horisations for medicinal pr oducts, requires the Commission 
to adopt appropriate arrangements for the ex amination of variati ons to the terms of 
marketing authorisations granted in acco rdance with Directives 2001/82/EC and 
2001/83/EC not yet covered by Commi ssion Regulation (EC) 1234/2008. It is 
therefore appropriate to extend the scope of Commission Regulation (EC) 1234/2008. 
The variations of all marketing authorisations  granted in the EU in accordance with the 
acquis should be subject to th e procedures laid down in  Commission Regulation (EC) 
No 1234/2008. 
                                                
 
1 OJ L 311. 28.11.2001, p. 1. 
2 OJ L 311. 28.11.2001, p. 67. 
3 OJ L 136. 30.4.2004, p. 1.  
EN 3   EN (2) The definition of variation s hould be clarified and updated in  particular to take into 
consideration the provisions of Regulat ion (EU) No 1235/2010 of the European 
Parliament and of the Council of 15 December 2010 amending, as regards 
pharmacovigilance of medicinal products for human use, Regulation (EC) No 
726/2004 laying down Community procedures for the authorisation and supervision of 
medicinal products for human and veterina ry use and establishing a European 
Medicines Agency, and Regulation (E C) No 1394/2007 on advanced therapy 
medicinal products4, and the provisions of Direc tive 2010/84/EU of the European 
Parliament and of the Council of 15 December 2010 amending, as regards 
pharmacovigilance, Directive 2001/83/EC  on the Community code relating to 
medicinal products for human use. 
(3) For reasons of consistency and with a vi ew to reducing the administrative burden, 
variations to purely national marketing authorisations shoul d be processed in 
accordance with the same principles that apply to variations of marketing authorisations granted under the mutual r ecognition procedure and the decentralised 
procedure. However, the possibilities for gr ouping variations shoul d be adapted to the 
specific characteristics of purely na tional marketing authorisations. 
(4) It should be possible to process variations to purely national mark eting authorisations 
in accordance with the worksharing proce dure under certain cond itions. Where the use 
of the worksharing procedure has lead to  the harmonisation of a section of the 
summary of product characterist ics, it should not be possibl e for the holder to later 
undermine the harmonisation achieved by submitting applications for variations to the section thus harmonised in some of  the concerned Member States only. 
(5) Grouping of several variations in a single submission is possible in some cases. It 
should be clarified that, where several vari ations are grouped, the procedure for the 
handling of the variations in  the group and the rules for the implementation of those 
variations should be th ose of the variation of the highest  grade. In order to facilitate 
the acceptance of complex groupings by the rele vant authorities, it should be possible 
to extend the assessment period. 
(6) The worksharing procedure is intended to avoid duplication of wo rk. Accordingly, it 
should be possible for competent authorities to process under the same procedure variations to purely national marketing au thorisations, varia tions to marketing 
authorisations granted under the mutual re cognition or decentralised procedure, and 
variations to centralised marketing authorisations. 
(7) The procedure for the variation of human influenza vaccines should be streamlined. 
Competent authorities should st ill be able to start the a ssessment in the absence of 
clinical and stability data a nd take a decision if no additi onal information is considered 
necessary. However, if clin ical and stability data is requested, the competent 
authorities should not be requ ired to take a decision unti l the assessment thereof has 
been finalised.  
(8) For medicinal products authorised under Re gulation (EC) No 726/2004, the refusal of 
the European Medicines Agency to accept a va riation should terminate the procedure. 
                                                
 
4 OJ L 348, 31.12.2010, p. 1.  
EN 4   EN Likewise, a Commission decisi on should not be required rega rding variations that do 
not amend the terms of the decision gr anting the marketing authorisation.  
(9) The European Medicines Agency has the expert ise to assess the need for urgent safety 
restrictions regarding medici nal products authorised under the centralised procedure. 
Marketing authorisation holders of medi cinal products author ised under Regulation 
(EC) No 726/2004 should therefore inform the Agency if they consider that urgent 
safety measures are necessary. 
(10) A proliferation of variation pr ocedures leading to frequent changes in the terms of the 
decision granting the marketing authorisation for centralised marketing authorisations 
has been identified. Changes that are critical  for public health should be reflected in 
the decision granting the marketing author isation promptly. However, other changes 
should be reflected in the decision granti ng the marketing authorisation according to 
timelines that ensure reasonable period ic updates of the decision granting the 
marketing authorisations while facilitating the identification of variations with the 
greatest impact on public health.  
(11) The principles governing the implementation of variations should be adjusted while 
keeping the principle that it should be possi ble for the marketing authorisation holder 
to implement certain variations prior to the relevant marketing authorisation being 
changed.  
(12) The measures provided for in this Regula tion are in accordance with the opinion of 
the Standing Committee on Medicinal Produc ts for Human Use and the Standing 
Committee on Veterinary Medicinal Products,  
HAS ADOPTED THIS REGULATION: 
Article 1 
Amendments to Regulation (EC) No 1234/2008 
Regulation (EC) 1234/2008 is amended as follows: 
(1) Article 1 is amended as follows: 
(a) paragraph 1 is replaced by the following: 
"1. This Regulation lays down provisions c oncerning the examination of variations 
to the terms of all marketing authorisations for medicinal products for human use and veterinary medicinal products granted in  accordance with Regulation (EC) No 
726/2004, Directive 2001/83/EC, Directiv e 2001/82/EC, and Council Directive 
87/22/EEC
 (5." 
(b) the following paragraph shall be inserted after paragraph (3): 
                                                 
5 * OJ L15, 17.1.1987, p. 38.  
EN 5   EN "3a. Chapter IIa shall apply only to vari ations to the term s of purely national 
marketing authorisations."  
(2) Article 2 is amended as follows: 
(a) paragraph 1 is replaced by the following: 
"1.'Variation to the terms of a marketing authorisation' or 'v ariation' means any 
amendment to: 
(a) the information referred to in Artic les 12(3) to 14 of Directive 2001/82 
and Annex I thereto, Articles 8(3) to 11 of Directive 2001/83 and Annex 
I thereto, Articles 6(2) and 31(2)  of Regulation (EC) No 726/2004, or 
Article 7of Regulati on (EC) No 1394/2007; 
(b) the terms of the decision granting th e marketing authorisation, including 
the summary of the product char acteristics and any conditions, 
obligations, or restrictions affect ing the marketing authorisation, or 
changes to the labelling or the package leaflet connected with changes to the summary of the product characteristics." 
(b) paragraph 8 is replaced by the following: 
“8. 'Urgent safety restriction' means an  interim change in the terms of the 
marketing authorisation due to new inform ation having a bearing on the safe use of 
the medicinal product.” 
(c) the following paragraph 9 is added: 
"9. 'Purely national marketing authorisa tion' means any marketing authorisation 
granted in accordance with Chapter 3 of Title III of Directive 2001/82/EC or Chapter 
3 of Title III of Directive 2001/83/EC that has no t been subject to complete 
harmonisation following a referral procedure."  
(3) Article 3 is amended as follows: 
(a) paragraph 2 is replaced by the following: 
"2. A variation which is not an extensio n and whose classification is undetermined 
after application of th e rules provided for in this Re gulation, taking into account the 
guidelines referred to in Article 4(1) and, where relevant, any recommendations 
delivered pursuant to Article 5, shall by de fault be considered a minor variation of 
type IB." 
(b) in paragraph 3, point (b) is replaced by the following: 
"(b) where the competent authority of the reference Member State as referred to in 
Article 32 of Directive 2001/82/EC and Article 28 of Directive 2001/83/EC 
(hereinafter "the reference Member State" ), in consultation with the other Member 
States concerned, or the Agency in the case of a centralised marketing authorisation, 
or the competent authority in  the case of a purely nationa l marketing authorisation, 
concludes, following the assessment of validity of a notification in accordance with  
EN 6   EN Article 9(1), Article 13b(1), or Article 15(1) and taking into account the 
recommendations delivered pursuant to Ar ticle 5, that the va riation may have a 
significant impact on the quality, safety or efficacy of the medicinal product 
concerned." 
(4) Article 4 is replaced by the following: 
"1. The Commission shall, after consulti ng the Member States, the Agency and 
interested parties, draw up guidelines on th e details of the vari ous categories of 
variations, on the operation of the procedures  laid down in Chapters II, IIa, III and IV 
of this Regulation, and on the documentatio n to be submitted pursuant to those 
procedures. 
2. The guidelines referred to in paragr aph 1 shall be regularly updated."  
(5) Article 5 is amended as follows: 
(a) paragraph 1 is replaced by the following: 
"1. Prior to the submission of a variatio n whose classification is not provided for 
in this Regulation, a holder may reques t a recommendation on the classification of 
the variation as follows: 
(a) to the Agency, where the variation re fers to a marketing authorisation 
granted under Regulation (EC) No 726/2004, 
(b) to the competent authority of the Member State concerned, where the 
variation refers to a purely na tional marketing authorisation, 
(c) to the competent authority of the re ference Member State, in the other 
cases. 
The recommendation referred to in the first subparagraph shall be consistent with the 
guidelines referred to in Article 4(1). It shall be delivered within 45 days following 
receipt of the request  and sent to the holder, the Agency, and the coordination group 
referred to in Article 31 of Directive 2001/82/EC or in Article 27 of Directive 
2001/83/EC.  
The 45-day period referred to in the second subparagraph may be extended by 20 
days where the relevant authority deems it necessary to consult with the coordination 
group ." 
(b) the following paragraph 1a is inserted after paragraph 1: 
"1a. Prior to the examination of a variat ion whose classificati on is not provided for 
in this Regulation, a competent authority of a Member State may request a recommendation on the classification of the variation to the coordination group. 
The recommendation referred to in the first subparagraph shall be consistent with the 
guidelines referred to in Article 4(1). It shall be delivered within 40 days following 
receipt of the request and sent to the holder, the Agency, and the competent 
authorities of all Member States."  
EN 7   EN (6) Article 7 is replaced by the following: 
"Article 7 
 Grouping of variations 
1. Where several variations are notified or applied for, a separa te notification or 
application in accordance with Chapters II, III, or Article 19 as appropriate 
shall be submitted in respect of each variation sought.  
2. By way of derogation from paragr aph 1, the following shall apply: 
(a) where the same minor variation(s) of t ype IA to the terms of one or more 
marketing authorisations owned by the sa me holder are notified at the same 
time to the same relevant authority, a si ngle notification as referred to in 
Articles 8 or 14 may cove r all such variations;  
(b) where several variations to the terms of  the same marketing authorisation are 
submitted at the same time, a single subm ission may cover all such variations 
provided that the variations  concerned fall within one  of the cases listed in 
Annex III;  
(c) where several variations to the terms of  the same marketing authorisation are 
submitted at the same time and the variati ons do not fall within one of the cases 
listed in Annex III, a single submission may cover all such variations provided 
that the competent authority  of the reference Member State in consultation with 
the competent authorities of the Member States concerned or, in the case of a 
centralised marketing authorisation, the Agency agrees to such single submission.  
The submission referred to in points (b) and (c) shall be made simultaneously to all 
relevant authorities by means of the following: 
(i) a single notification in accordance with  Articles 9 or 15 where at least one of 
the variations is a minor variation of type  IB and the remaining variations are minor 
variations; 
(ii) a single application in accordance with Articles 10 or 16 where at least one of 
the variations is a major variation of t ype II and none of the variations is an 
extension; 
(iii) a single application in accordance w ith Article 19 where at least one of the 
variations is an extension." 
(7) In Article 9, the following paragraph 5 is added: 
"5. This Article shall not apply where a t ype IB variation request is submitted in a 
grouping that includes a variation type II a nd does not contain an  extension. In such 
case, the prior approval procedur e in Article 10 shall apply.   
EN 8   EN This Article shall not apply where a type  IB variation request is submitted in a 
grouping that includes an exte nsion. In such case, the pr ocedure in Article 19 shall 
apply."  
(8) Article 10 is amended as follows: 
(a) In paragraph 2, the second subparagraph is replaced by the following: 
"The competent authority of the refere nce Member State may reduce the period 
referred to in the first subparagraph, having regard to the urgency of the matter, or 
extend it to 90 days for vari ations listed in Part 1 of  Annex V or for grouping of 
variations in accordance with Article 7(2)(c)." 
(b) The following paragraph 6 is added: 
"6. This Article shall not apply where a t ype II variation request is submitted in a 
grouping that includes an exte nsion. In such case, the pr ocedure in Article 19 shall 
apply."  
(9) Article 12 is amended as follows: 
(a) paragraphs 3, 4 and 5 are replaced by the following: 
"3. The competent authority of the reference Member State shall assess the 
application submitted. Where deemed nece ssary, the competent authority of the 
reference Member State may request addi tional data to the holder in order to 
complete its assessment. 
4. The competent authority shall prepare a decision and an assessment report 
within 45 days from the rece ipt of a valid application. 
The 45–day period referred to in the first subparagraph shall be suspended from the 
moment when the additional data referred to  in paragraph 3 is requested until the 
data is submitted. 
5. Within 12 days from the receipt of th e decision and the assessment report of 
the competent authority of th e reference Member State, the relevant authorities shall 
adopt a decision accordingly and inform th e competent authority  of the reference 
Member State and the holder thereof." 
(b)  paragraph 6 is deleted. 
(10) The following Chapter IIa is  inserted after Article 13:  
EN 9   EN "CHAPTER IIa 
VARIATIONS TO PURELY NATIONAL  MARKETING AUTHORISATIONS  
Article 13a 
Notification procedure for minor variations of type IA 
1. Where a minor variation of type IA is ma de, the holder shall submit to the competent 
authority a notification containing the elemen ts listed in Annex IV. This notification 
shall be submitted within 12 months following the implementation of the variation. 
However, the notification shall be submitte d immediately after the implementation of 
the variation in the case of minor variati ons requiring immediat e notification for the 
continuous supervision of th e medicinal product concerned.  
2. Within 30 days following receipt of the notification, the measures provided for in 
Article 13e shall be taken. 
Article 13b 
Notification procedure for minor variations of type IB 
1. The holder shall submit to the competen t authority a notifi cation containing the 
elements listed in Annex IV.  
If the notification fulfils th e requirement laid down in the first subparagraph, the 
competent authority shall acknowledg e receipt of a valid notification. 
2. If within 30 days followi ng the acknowledgement of receip t of a valid notification, 
the competent authority ha s not sent the ho lder an unfavourable opinion, the 
notification shall be deemed accepted by the competent authority. 
Where the notification is accepted by the co mpetent authority, the measures provided 
for in Article 13e shall be taken. 
3. Where the competent authority is of th e opinion that the notification cannot be 
accepted, it shall inform the holder, stat ing the grounds on which its unfavourable 
opinion is based. 
Within 30 days following the receipt of  the unfavourable opinion, the holder may 
submit to the competent authority an amended notification in order to take due account of the grounds laid down in that opinion. 
If the holder does not amend the notifi cation in accordance with the second 
subparagraph, the notification shall be deemed rejected.  
EN 10   EN 4. Where an amended notification has been submitted, the competent authority shall 
assess it within 30 days following its receipt and the measures provided for in Article 13e shall be taken. 
5. This Article shall not apply where a type  IB variation request is submitted in a 
grouping that includes a variation type II a nd does not contain an  extension. In such 
case, the prior approval procedur e in Article 13c shall apply. 
This Article shall not apply where a type  IB variation request is submitted in a 
grouping that includes an exte nsion. In such case, the pr ocedure in Article 19 shall 
apply. 
Article 13c 
‘Prior Approval’ procedure for major variations of type II 
1. The holder shall submit to the competent authority an application containing the 
elements listed in Annex IV. 
If the application fulfils the requirement s laid down in the fi rst subparagraph, the 
competent authority shall acknowledge receipt of a valid application.  
2. Within 60 days following the acknowledgement  of receipt of a valid application, the 
competent authority shall conclude the assessment.  
The competent authority may reduce the peri od referred to in the first subparagraph, 
having regard to the urgency of the matter, or extend it to 90 days for variations 
listed in Part 1 of Annex V or for grouping of variations in acco rdance with Article 
13d(2)(c).  
The period referred to in the first subparagraph shall be 90 days for variations listed 
in Part 2 of Annex V. 
3. Within the periods referred to in paragr aph 2, the competent authority may request 
the holder to provide supplementary info rmation within a time limit set by the 
competent authority. In this case the pr ocedure shall be su spended until such 
supplementary information has been pr ovided and the compet ent authority may 
extend the period referred to in paragraph 2. 
4. Within 15 days after the conclusion of th e assessment, the measures provided for in 
Article 13e shall be taken. 
5. This Article shall not apply where a type  II variation request is submitted in a 
grouping that includes an exte nsion. In such case, the pr ocedure in Article 19 shall 
apply.   
EN 11   EN Article 13d 
Grouping of variations to purely na tional marketing authorisations 
1. Where several variations are notified or applied for, a separa te notification or 
application in accordance with Articles 13a, 13b, 13c, or 19 as appropriate shall be submitted to each competent authority in  respect of each variation sought. 
2. By way of derogation from paragr aph 1 the following shall apply: 
(a) where the same minor vari ation(s) of type IA to the terms of one or more 
marketing authorisations owned by the sa me holder are notified at the same 
time to the same relevant authority, a si ngle notification as referred to in 
Articles 13a may cover all such variations; 
(b) where several variations to the terms of the same marketing authorisation are 
submitted at the same time to the comp etent authority, a single submission may 
cover all such variations provided that the variations concerned fall within one 
of the cases listed in Annex III; 
(c) where one or more variations to the terms of one or more marketing 
authorisations owned by the same holde r are submitted at the same time to the 
competent authority and they are not covered under subparagraphs (a) or (b), a 
single submission may cover all such va riations provided that the competent 
authority agrees to such single submission. 
The submission referred to in points (b) and (c) shall be made by means of the 
following: 
(i) a single notification in accordance w ith Article 13b where at least one of the 
variations is a minor varia tion of type IB and the rema ining variations are minor 
variations; 
(ii) a single application in accordance with Article 13c where at least one of the 
variations is a major variati on of type II and none of the va riations is an extension; 
(iii) a single application in accordance w ith Article 19 where at least one of the 
variations is an extension. 
Article 13e 
Measures to close the procedu res of Articles 13a to 13c 
Where reference is made to this Article, the competent authority shall take the following 
measures: 
(a) it shall inform the holder as to whether the variation is accepted or rejected;  
(b) where the variation is rej ected, it shall inform the hol der of the grounds for the 
rejection;  
EN 12   EN (c) where necessary, it shall amend th e decision granting the marketing 
authorisation in accordance with the accep ted variation within the time limit 
laid down in paragraph 1 of Article 23.  
Article 13f  
Human influenza vaccines 
1. By way of derogation from Article 13c, the procedure laid down in paragraphs 2 to 6 
shall apply to the examination of variations concerning changes to the active substance for the purposes of the annual  update of a human influenza vaccine. 
2. The holder shall submit to the competent authority an application containing the 
elements listed in Annex IV. 
If the application fulfils the requirement s laid down in the fi rst subparagraph, the 
competent authority shall acknowledge receipt of a valid application.  
3. The competent authority shall assess the application submitted. Where deemed 
necessary, the competent authority may request  additional data to the holder in order 
to complete its assessment. 
4. The competent authority shall adopt a deci sion within 45 days from the receipt of a 
valid application and shall take the m easures provided for in Article 13e.  
The 45-day period referred to in the first subparagraph shall be suspended from the 
moment when the additional data referred to  in paragraph 3 is requested until the 
data is submitted." 
(11) Article 15 is amended as follows: 
(a) in paragraph 3, the third subparagraph is replaced by the following: 
"If the holder does not amend the notification in accordance with the second 
subparagraph, the notification sh all be deemed rejected." 
(b) The following paragraph 5 is added: 
"5. This Article shall not apply where a t ype IB variation request is submitted in a 
grouping that includes a variation type II a nd does not contain an  extension. In such 
case, the prior approval procedur e in Article 16 shall apply.  
This Article shall not apply where a type  IB variation request is submitted in a 
grouping that includes an exte nsion. In such case, the pr ocedure in Article 19 shall 
apply." 
(12) Article 16 is amended as follows: 
(a) in paragraph 2, the second subparagraph is replaced by the following:  
EN 13   EN "The Agency may reduce the period referre d to in the first subparagraph, having 
regard to the urgency of the matter, or extend  it to 90 days for vari ations listed in Part 
1 of Annex V or for grouping of variations  in accordance with Article 7(2)(c)." 
(b) the following paragraph 5 is added: 
"5. This Article shall not apply where a t ype II variation request is submitted in a 
grouping that includes an exte nsion. In such case, the pr ocedure in Article 19 shall 
apply." 
(13) Article 17 is repl aced by the following: 
"Article 17 
Measures to close the proce dures of Articles 14 to 16 
1. Where reference is made to this Article, the Agency shall take the following 
measures:  
(a) it shall inform the holder of the outcome of the assessment;  
(b) where the variation is rej ected, it shall inform the hol der of the grounds for the 
rejection; 
(c) where the outcome of the assessment is favourable and the variation affects the 
terms of the Commission decision gran ting the marketing authorisation, the 
Agency shall transmit to the Commi ssion its opinion and the grounds for its 
opinion as well as the revise d versions of the document s referred to in Article 
9(4) of Regulation (EC) No 726/2004. 
2. In the cases identified under paragraph 1(c), the Commission, having regard to the 
opinion from the Agency and within the time limit foreseen in Article 23(2), shall amend where necessary the decision gran ting the marketing authorisation. The 
Community Register of  Medicinal Products provided fo r in Article 13(1) and Article 
38(1) of Regulation (EC) No 726/2004 shall be updated accordingly." 
(14) Article 18 is amended as follows: 
(a) paragraphs 3, 4, 5 and 6 are replaced by the following: 
"3. The Agency shall assess the application submitted. Where deemed necessary, 
the Agency may request additional da ta to complete its assessment.  
4. Within 55 days from the receipt of a valid application, the Agency shall adopt 
an opinion. The Agency's opinion on the a pplication shall be transmitted to the 
applicant. Where the Agency's opinion is favourable, the Agency shall also transmit 
to the Commission its opinion and the grounds  for its opinion as well as the revised 
versions of the documents referred in Ar ticle 9(4) of Regulation (EC) No 726/2004.   
EN 14   EN 5. The 55-day period referred to in paragraph 4 shall be suspended from the 
moment when the additional data referred to  in paragraph 3 is requested until the 
data is submitted.  
6. Having regard to the favourable opini on of the Agency, the Commission shall 
amend where necessary the decision gran ting the marketing authorisation. The 
Community Register of Medi cinal Products provided for in  Article 13(1) shall be 
updated accordingly. " 
(b)  paragraph 7 is deleted. 
(15) Article 20 is amended as follows: 
(a) paragraph 1 is replaced by the following: 
"1. By way of derogation from Articles 7(1), 9, 10, 13b, 13c, 13d, 15 and 16 the 
holder of a marketing authorisation may c hoose to follow the worksharing procedure 
laid down in paragraphs 3 to  9 in the following cases:  
(a) for marketing authorisations referred to  in Chapters II and III, where a minor 
variation of type IB, a major variation of type II, or a gr oup of variations as provided 
for in Article 7(2) (b) or (c) that does not contain any extension relates to several 
marketing authorisations owned by the same holder;  
(b) for purely national marketing authorisati ons referred to in Chapter IIa, where a 
minor variation of type IB or a major vari ation of type II relates to one or more 
marketing authorisation(s) owned by the same holder, or where the reference 
authority agrees to process a group of variations relate d to one or more marketing 
authorisation(s) of the same holder under worksharing. 
The reference authority or, in the case of  purely national marketing authorisations, 
the competent authority may refuse to process a submission under the worksharing 
procedure where the same change(s) to diffe rent marketing authorisations require the 
submission of individual supportive data fo r each medicinal product concerned or a 
separate product-specific assessment."  
(b) in paragraph 3, the first and second subparagraphs are replaced by the 
following: 
"3. The holder shall submit to all relevant authorities an application containing the 
elements listed in Annex IV, with an indica tion of the preferred reference authority.  
The coordination group shall choose a refere nce authority. If the application fulfils 
the requirements laid down in the first s ubparagraph, that reference authority shall 
acknowledge receipt of a valid application."  
(c) paragraphs 4 and 5 are replaced by the following: 
"4. The reference authority shall issue an  opinion on a valid application as referred 
to in paragraph 3 within one of the following periods:   
EN 15   EN (a) a period of 60 days following ack nowledgement of receipt of a valid 
application in the case of minor variati ons of type IB or major variations 
of type II; 
(b) a period of 90 days following ack nowledgement of receipt of a valid 
application in the case of  variations listed in  Part 2 of Annex V. 
5. The reference authority may reduce the period referred to in point (a) of 
paragraph 4, having regard to  the urgency of the matter, or extend it to 90 days for 
variations listed in Part 1 of Annex V or for grouping of variations in accordance 
with Article 7(2)(c) or  Article 13d(2)(c)." 
(d) paragraphs 7 and 8 are replaced by the following: 
"7. Where the reference authority is the Agency, Article 9(1) and (2) and Article 
34(1) and (2) of Regulation (EC) No 726/2004 shall apply to the opinion referred to 
in paragraph 4.  
The Agency's opinion on the application shall be transmitted to the applicant and the 
Member States, together with the asse ssment report. Where the outcome of the 
assessment is favourable and the variati on affects the terms of the Commission 
decision granting the marketing authorisati on, the Agency shall also transmit to the 
Commission its opinion and the grounds fo r its opinion as well as the revised 
versions of the documents referred in Ar ticle 9(4) of Regulation (EC) No 726/2004.  
Where the Agency issues a favourable  opinion, the following shall apply: 
(a) if the opinion recommends the variat ion to the terms of a Commission decision 
granting the marketing authorisation, th e Commission shall, having regard to 
the final opinion and within the time limits  foreseen in Article 23(2), amend the 
decision(s) accordingly. The Community  Register of Medicinal Products 
provided for in Article 13(1) and Article 38(1) of Regulation (EC) No 
726/2004 shall be updated accordingly; 
(b) the Member States concerned shall, within 60 days following receipt of the 
final opinion of the Agency, approve that final opinion, inform the Agency 
thereof and, where necessary, amend the marketing authorisations concerned accordingly, provided that the documents necessary for the amendment of the marketing authorisation have been transmitted to the Member States concerned. 
8. Where the reference authority is the co mpetent authority of a Member State: 
(a) it shall send its opinion to the holde r and to all rele vant authorities; 
(b) without prejudice to Article 13 and within 60 days following receipt of the 
opinion, the relevant authorities sha ll approve that opinion, inform the 
reference authority and amend where n ecessary the marketing authorisations 
concerned accordingly, provided that the documents necessary for the amendment of the marketing authoris ation have been transmitted to the 
Member States concerned."  
EN 16   EN (e) the following paragraph 10 is inserted after paragraph 9: 
"10. Where harmonisation of a section of th e summary of product characteristics of a 
purely national marketing authorisation has been achieved through a worksharing 
procedure, any subsequent variation s ubmission affecting the harmonised section 
shall be transmitted simultaneously to all Member States concerned."  
(16) In Article 21, paragraph 1 is replaced by the following: 
"1. By way of derogation from Chapter I, II, IIa, and III, where a pandemic situation 
with respect to human influenza is duly recognised by the World Health Organisation 
or by the Union in the framework of Decision 2119/98/EC of the European Parliament and of the Council,
6the relevant authorities or, in the case of centralised 
marketing authorisations, the Commission may exceptionally and temporarily accept 
a variation to the terms of a marketing au thorisation for a human influenza vaccine, 
where certain non-clinical or clinical data are missing." 
(17) In Article 22, paragraph 1 is replaced by the following: 
"1. Where, in the event of a ri sk to public health in the case of medicinal products for 
human use or, in the case of veterinary medicinal products, in the event of a risk to 
human or animal health or to the envi ronment, the holder takes urgent safety 
restrictions on its own initiativ e, it shall forthwith inform all relevant authorities and, 
in the case of a centralised marketing authorisation, the Agency. 
If the relevant authority or, in the case of a centralised marketing authorisation, the 
Agency has not raised objections within  24 hours following receipt of that 
information, the urgent safety restrictions shall be deemed accepted."  
(18) Article 23 is amended as follows: 
"Article 23 
Amendments to the decision granting the marketing authorisation  
(a) paragraph 1 is replaced by the following: 
"1. Amendments to the decision granti ng the marketing authorisation resulting 
from the procedures laid down in Chapters II and IIa shall be made: 
 (a) within 30 days following receipt of  the information referred to in Article 
11(1)(c) and Article 13e(c), where the c oncerned variation leads to a six-month 
extension of the period referred to in Artic les 13(1) and (2) of Regulation (EC) No 
469/20097in accordance with Article 36 of  Regulation (EC) No 1901/2006; 
 (b) within two months following receipt of  the information referred to in Article 
11(1)(c) and Article 13e(c), in the case of major variations of type II;  
                                                 
6 OJ L 268, 3.10.1998, p. 1. 
7 OJ L 152, 16.06.2009, p. 1.  
EN 17   EN  (c) within six months following receipt of  the information referred to in Article 
11(1)(c) and Article 13e(c), in the other cases." 
(b) paragraph 2 is replaced by the following: 
"2. Amendments to the decision granti ng the marketing authorisation resulting 
from the procedures laid down in Chapter III shall be made: 
 (a) within two months following receipt of  the information referred to in Article 
17(1)(c), where the concerned variation leads to a six-m onth extension of the period 
referred to in Articles 13(1) and (2) of  Regulation (EC) No 469/2009 in accordance 
with Article 36 of Regul ation (EC) No 1901/2006;  
 (b) within two months following receipt of  the information referred to in Article 
17(1)(c) for the following variations:  
(i) variations related to the addition of a new therapeutic indication or to 
the modification of an existing one; 
(ii) variations related to the a ddition of a new contraindication; 
(iii) variations related to a change in posology; 
(iv) variations related to the addition of an specie or the modification of an 
existing one for veterina ry medicinal products; 
(v) variations concerning the replacemen t or addition of a serotype, strain, 
antigen or combination of serotypes, strains or antigens for a veterinary 
vaccine;   
(vi) variations related to changes to the active substance of a seasonal, pre-
pandemic or pandemic vaccine against human influenza; 
(vii) variations related to changes to the withdrawal period  for a veterinary 
medicinal product; 
(viii) other type II variations that are intended to implement changes to the 
terms of the marketing authorisation due to a significant public health concern or significant animal health or environmen tal concern in the case of veterinary 
medicinal products.  
(c) within twelve months following receipt of  the information referred to in Article 
17(1)(c) in the other cases. 
 The Agency shall determine the variations referred to in point (b)(viii) and provide 
reasons for such determination." 
(a) The following paragraph 3 is added: 
"3. Where the decision granting a marketing authorisation is amended as a result 
of one of the procedures laid down in Ch apters II, IIa, III and IV, the relevant  
EN 18   EN authority or, in the case of centralised marketing authorisations, the Commission 
shall notify the amended decision without delay to the holder." 
(19) Article 24 is repl aced by the following: 
"Article 24 
Implementation of variations 
1. Minor variations of type IA may be im plemented any time before completion of the 
procedures laid down in Articles 8, 13a, and 14. 
Where a notification concerning one or seve ral minor variations of type IA is 
rejected, the holder shall cease to apply the concerned variation(s)  immediately after 
receipt of the information referred to in Articles 11(1)(a), 13e (a), and 17(1)(a). 
2. Minor variations of type IB may only be implemented in the following cases: 
 (a) for variations submitted in accordance with the procedures laid down in 
Chapter II, after the competent authority of  the reference Member State has informed 
the holder that it has accepte d the notification pursuant to  Article 9, or after the 
notification is deemed accepted pursuant to Article 9(2);  
 (b) for variations submitted in accordance with the procedures laid down in 
Chapter IIa, after the relevant authority ha s informed the holder that it has accepted 
the notification pursuant to Ar ticle 13b, or after the notif ication is deemed accepted 
pursuant to Article 13b(2); 
 (c) for variations submitted in accordance with the procedures laid down in 
Chapter III, after the Agency has informed  the holder that its opinion referred to in 
Article 15 is favourable, or after that opi nion is deemed favourable pursuant to 
Article 15(2). 
3. Major variations of type II may only be  implemented in the following cases:  
 (a) for variations submitted in accordance with the procedures laid down in 
Chapter II, 30 days  after the competent authority of the reference Member State has 
informed the holder that it has accepted th e variation pursuant to Article 10. Where 
an arbitration procedure has been initiated  in accordance with Article 13, the holder 
shall not implement the variation until the arbitration procedure has concluded that 
the variation is accepted. 
 (b) for variations submitted in accordance with the procedures laid down in 
Chapter IIa, after the competent author ity has informed the holder that it has 
accepted the variation pursuant to Article 13c. 
 (c) for variations submitted in accordance with the procedures laid down in 
Chapter III, after the Agency has informed  the holder that its opinion referred to in 
Article 16 is favourable, unless the variation is one referred  to in Article 23(2)(b).  
EN 19   EN  Variations referred to in Article 23(2)(b) may only be implemented after the 
Commission has amended the decision gran ting the marketing authorisation and 
notified the holder thereof. 
4. Variations submitted in accordance with Article 20, may only be implemented 60 
days after the reference authority referred to in Article 20 has informed the holder that its opinion is favourable, unless an ar bitration procedure has been initiated in 
accordance with Article 13, or unless the procedure concerns a variation to a 
centralised marketing authorisation as  referred to in Article 23(2)(b). 
 Where an arbitration procedure has been initiated in accordance with Article 13, or 
where the worksharing procedure concerns a variation to a centralised marketing 
authorisation as referred to in Article 23( 2)(b), the holder shall not implement the 
variation until the arbitration procedure ha s concluded that the variation is accepted, 
or until the Commission D ecision amending the decision  granting the marketing 
authorisation has been adopted. 
5. An extension may only be implemented after the relevant authority or, in the case of 
extensions to a centralised  marketing authorisation, th e Commission has amended the 
decision granting the marketing authorisa tion and notified the holder accordingly". 
(20) The following Article 24a is inserted after Article 24: 
 "Article 24a 
Application of national provisio ns on variations to purely na tional marketing authorisations 
Member States that, in accordance with Arti cle 23b(4) of Directiv e 2001/83, may continue to 
apply their national provision s on variations to certai n purely national marketing 
authorisations are listed in Annex VI to this Regulation." 
(21) The Annex set out in the A nnex to this Regulation is added. 
Article 2 
Entry into force and application 
1. This Regulation shall enter into force on the twentieth day following that of its 
publication in the Official Journal of the European Union . 
2. It shall apply from [60 days fo llowing that of its publication].  
 However, points (15), (16), 18(a) and (c) and 20 of Artic le 1 shall apply from [8 
months following publication in the Offici al Journal of the European Union] 
This Regulation shall be binding in  its entirety and directly applicable in all Member States.  
EN 20   EN Done at Brussels,  
 For the Commission 
 On behalf of the President  […]  [Position]  
EN 21   EN "ANNEX VI  
List of Member States re fered in Article 1(20): 
the Republic of Bulgaria the French Republic."