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

‘1 This Regulation lays down provisions concerning 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, Directive 2001/82/EC, and Council Directive 87/22/EEC .

‘3a Chapter IIa shall apply only to variations to the terms of purely national marketing authorisations.’;

‘1 “Variation to the terms of a marketing authorisation” or “variation” means any amendment to: (a) the information referred to in Articles 12(3) to 14 of Directive 2001/82/EC and Annex I thereto, Articles 8(3) to 11 of Directive 2001/83/EC and Annex I thereto, Articles 6(2) and 31(2) of Regulation (EC) No 726/2004, or Article 7 of Regulation (EC) No 1394/2007; (b) the terms of the decision granting the marketing authorisation for a medicinal product for human use, including the summary of the product characteristics and any conditions, obligations, or restrictions affecting the marketing authorisation, or changes to the labelling or the package leaflet connected with changes to the summary of the product characteristics; (c) the terms of the decision granting the marketing authorisation for a veterinary medicinal product, including the summary of the product characteristics and any conditions, obligations, or restrictions affecting the marketing authorisation, or changes to the labelling or the package leaflet.’;

‘8 “Urgent safety restriction” means an interim change in the terms of the marketing authorisation due to new information having a bearing on the safe use of the medicinal product.’;

‘9 “Purely national marketing authorisation” means any marketing authorisation granted by a Member State in accordance with the acquis outside the mutual recognition or decentralised procedure and that has not been subject to a complete harmonisation following a referral procedure.’;

‘2 A variation which is not an extension and whose classification is undetermined after application of the rules provided for in this Regulation, taking into account the guidelines referred to in Article 4(1) and, where relevant, any recommendations delivered pursuant to Article 5, shall by default be considered a minor variation of type IB.’;

1 The Commission shall, after consulting the Member States and the Agency, draw up guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of this Regulation, and on the documentation to be submitted pursuant to those procedures.

2 The guidelines referred to in paragraph 1 shall be regularly updated.’;

1 Where several variations are notified or applied for, a separate 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 paragraph 1, the following shall apply: (a) where the same minor variation(s) of type IA to the terms of one or more marketing authorisations owned by the same holder are notified at the same time to the same relevant authority, a single notification as referred to in Article 8 or 14 may cover all such variations; (b) where several variations to the terms of the same marketing authorisation are submitted at the same time, 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 several variations to the terms of the same marketing authorisation are submitted at the same time and the variations 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 subparagraphs (b) and (c) shall be made simultaneously to all relevant authorities by means of the following: (i) a single notification in accordance with Article 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 Article 10 or 16 where at least one of the variations is a major variation of type II and none of the variations is an extension; (iii) a single application in accordance with Article 19 where at least one of the variations is an extension.’;

1 Where a minor variation of type IA is made, the holder shall submit to the competent authority a notification containing the elements listed in Annex IV. This notification shall be submitted within 12 months following the implementation of the variation. However, the notification shall be submitted immediately after the implementation of the variation in the case of minor variations requiring immediate notification for the continuous supervision of the medicinal product concerned.

2 Within 30 days following receipt of the notification, the measures provided for in Article 13e shall be taken.

1 The holder shall submit to the competent authority a notification containing the elements listed in Annex IV. If the notification fulfils the requirement laid down in the first subparagraph, the competent authority shall acknowledge receipt of a valid notification.

2 If within 30 days following the acknowledgement of receipt of a valid notification, the competent authority has not sent the holder an unfavourable opinion, the notification shall be deemed accepted by the competent authority. Where the notification is accepted by the competent authority, the measures provided for in Article 13e shall be taken.

3 Where the competent authority is of the opinion that the notification cannot be accepted, it shall inform the holder, stating 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 notification in accordance with the second subparagraph, the notification shall be deemed rejected.

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 and does not contain an extension. In such case, the prior approval procedure in Article 13c shall apply. This Article shall not apply where a type IB variation request is submitted in a grouping that includes an extension. In such case, the procedure in Article 19 shall apply.

1 The holder shall submit to the competent authority an application containing the elements listed in Annex IV. If the application fulfils the requirements laid down in the first 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 period 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 accordance 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 paragraph 2, the competent authority may request the holder to provide supplementary information within a time limit set by the competent authority. In this case the procedure shall be suspended until such supplementary information has been provided and the competent authority may extend the period referred to in paragraph 2.

4 Within 30 days after the conclusion of the 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 extension. In such case, the procedure in Article 19 shall apply.

1 Where several variations are notified or applied for, a separate notification or application in accordance with Articles 13a, 13b, 13c, or 19 as appropriate shall be submitted to the competent authority in respect of each variation sought.

2 By way of derogation from paragraph 1 the following shall apply: (a) where the same minor variation(s) of type IA to the terms of one or more marketing authorisations owned by the same holder are notified at the same time to the same competent authority, a single notification as referred to in Article 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 same competent 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 the same variation(s) to the terms of one or more marketing authorisations owned by the same holder are submitted at the same time to the same competent authority and they are not covered under subparagraph (a) or (b), a single submission may cover all such variations 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 with Article 13b 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 Article 13c where at least one of the variations is a major variation of type II and none of the variations is an extension; (iii) a single application in accordance with Article 19 where at least one of the variations is an extension.

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 rejected, it shall inform the holder of the grounds for the rejection; (c) where necessary, it shall amend the decision granting the marketing authorisation in accordance with the accepted variation within the time limit laid down in paragraph 1 of Article 23.

1 By way of derogation from Article 13c, the procedure laid down in paragraphs 2 to 4 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 requirements laid down in the first 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 decision within 45 days from the receipt of a valid application and shall take the measures 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.’;

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 rejected, it shall inform the holder 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 granting the marketing authorisation, the Agency shall transmit to the Commission its opinion and the grounds for its opinion as well as the revised versions of the documents referred to in Article 9(4) or Article 34(4) of Regulation (EC) No 726/2004 as appropriate.

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(1a), shall amend where necessary the decision 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 updated accordingly.’;

The statement indicating compliance with the agreed completed paediatric investigation plan provided for under Article 28(3) of Regulation (EC) No 1901/2006 shall be included within the technical dossier of the marketing authorisation. The relevant authority shall provide the holder with a confirmation that the statement is included in the technical dossier within 30 days after the relevant assessment has been concluded.’;

1 Minor variations of type IA may be implemented any time before completion of the procedures laid down in Articles 8, 13a and 14. Where a notification concerning one or several 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 accepted 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 has informed the holder that it has accepted the notification pursuant to Article 13b, or after the notification 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 opinion is deemed favourable pursuant to Article 15(2); (d) for variations submitted in accordance with the procedure laid down in Article 20, after the reference authority has informed the holder that its opinion is favourable.

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 the variation pursuant to Article 10, under the condition that the documents necessary for the amendment to the marketing authorisation have been provided to the Member States concerned. 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 authority 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(1a)(a). Variations referred to in Article 23(1a)(a) may only be implemented after the Commission has amended the decision granting the marketing authorisation and notified the holder thereof; (d) for variations submitted in accordance with the procedure laid down in Article 20, 30 days after the reference authority has informed the holder that its opinion is favourable, under the condition that the documents necessary for the amendment to the marketing authorisation have been provided to the Member States concerned; unless an arbitration 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(1a)(a). 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(1a)(a), the holder shall not implement the variation until the arbitration procedure has concluded that the variation is accepted, or until the Commission Decision amending the decision granting the marketing authorisation has been adopted.

4 An extension may only be implemented after the relevant authority or, in the case of extensions to a centralised marketing authorisation, the Commission has amended the decision granting the marketing authorisation and notified the holder accordingly.

5 Urgent safety restrictions and variations which are related to safety issues shall be implemented within a time frame agreed by the holder and the relevant authority and, in the case of a centralised marketing authorisation, the Agency. By way of derogation from the first subparagraph, urgent safety restrictions and variations related to safety issues which concern marketing authorisations granted in accordance with Chapter 4 of Directive 2001/82/EC or Chapter 4 of Directive 2001/83/EC shall be implemented within a time frame agreed by the holder and the competent authority of the reference Member State, in consultation with the other relevant authorities.’;

Member States that, in accordance with Article 23b(4) of Directive 2001/83/EC, may continue to apply their national provisions on variations to certain purely national marketing authorisations are listed in Annex VI to this Regulation.’;

From 2 November 2012, the following changes shall apply: (a) in Article 23(1) of Regulation (EC) No 1234/2008, the reference to ‘Chapters II and III’ is replaced by ‘Chapter II’; (b) in Article 23(1) of Regulation (EC) No 1234/2008, subparagraph (a) is deleted.

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 2 November 2012. However, points (10), (15), (18)(a) and (c), (21), (22) and (23) of Article 1 shall apply from 4 August 2013.