1.   This Regulation lays down provisions concerning the examination of variations to the terms of the following marketing authorisations for medicinal products for human use and veterinary medicinal products:

2.   This Regulation shall not apply to transfers of a marketing authorisation from one marketing authorisation holder (hereinafter holder) to another.

3.   Chapter II shall apply only to variations to the terms of marketing authorisations granted in accordance with Directive 87/22/EEC, Chapter 4 of Directive 2001/82/EC or Chapter 4 of Directive 2001/83/EC.

4.   Chapter III shall apply only to variations to the terms of marketing authorisations granted in accordance with Regulation (EC) No 726/2004 (hereinafter centralised marketing authorisations).

1.   In relation to any variation which is not an extension the classification laid down in Annex II shall apply.

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 point (a) of Article 4(1) and, where relevant, any recommendations delivered pursuant to Article 5, shall by default be considered a minor variation of type IB.

3.   By way of derogation from paragraph 2, a variation which is not an extension and whose classification is undetermined after application of the rules provided for in this Regulation shall be considered a major variation of type II in the following cases:

1.   The Commission shall, after consulting the Member States, the Agency and interested parties, draw up:

2.   Guidelines referred to in point (a) of paragraph 1 shall be drawn up by the date referred to in the second subparagraph of Article 28 and shall be regularly updated, taking into account the recommendations delivered in accordance with Article 5 as well as scientific and technical progress.

1.   Prior to submission or examination of a variation whose classification is not provided for in this Regulation, a holder or a competent authority of a Member State may request the coordination group referred to in Article 31 of Directive 2001/82/EC or in Article 27 of Directive 2001/83/EC (hereinafter the coordination group) or, in the case of a variation to the terms of a centralised marketing authorisation, the Agency to provide a recommendation on the classification of the variation.

The recommendation referred to in the first subparagraph shall be consistent with the guidelines referred to in point (a) of Article 4(1). It shall be delivered within 45 days following receipt of the request and sent to the holder, the Agency and the competent authorities of all Member States.

2.   The Agency and the two coordination groups referred to in paragraph 1 shall cooperate to ensure the coherence of the recommendations delivered in accordance with that paragraph and publish those recommendations after deletion of all information of commercial confidential nature.

1.   Where several variations are notified or applied for, a separate notification or application as laid down in Chapters II, III and IV shall be submitted in respect of each variation sought.

2.   By way of derogation from paragraph 1, the following shall apply:

The submission referred to in point (b) of the first subparagraph shall be made by means of the following:

1.   Where a minor variation of type IA is made, the holder shall submit simultaneously to all relevant authorities 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 11 shall be taken.

1.   The holder shall submit simultaneously to all relevant authorities a notification containing the elements listed in Annex IV.

If the notification fulfils the requirement laid down in the first subparagraph, the competent authority of the reference Member State shall, after consulting the other Member States concerned, acknowledge receipt of a valid notification.

2.   If within 30 days following the acknowledgement of receipt of a valid notification, the competent authority of the reference Member State has not sent the holder an unfavourable opinion, the notification shall be deemed accepted by all relevant authorities.

Where the notification is accepted by the competent authority of the reference Member State, the measures provided for in Article 11 shall be taken.

3.   Where the competent authority of the reference Member State is of the opinion that the notification cannot be accepted, it shall inform the holder and the other relevant authorities, 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 all relevant authorities 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 by all relevant authorities and the measures provided for in Article 11 shall be taken.

4.   Where an amended notification has been submitted, the competent authority of the reference Member State shall assess it within 30 days following its receipt and the measures provided for in Article 11 shall be taken.

1.   The holder shall submit simultaneously to all relevant authorities an application containing the elements listed in Annex IV.

If the application fulfils the requirements laid down in the first subparagraph, the competent authority of the reference Member State shall acknowledge receipt of a valid application and inform the holder and the other relevant authorities that the procedure starts from the date of such acknowledgement.

2.   Within 60 days following the acknowledgement of receipt of a valid application, the competent authority of the reference Member State shall prepare an assessment report and a decision on the application, which shall be communicated to the other relevant authorities.

The competent authority of the reference 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 variations listed in Part 1 of Annex V.

The period referred to in the first subparagraph shall be 90 days for variations listed in Part 2 of Annex V.

3.   Within the period referred to in paragraph 2, the competent authority of the reference Member State may request the holder to provide supplementary information within a time limit set by that competent authority. In this case:

4.   Without prejudice to Article 13 and within 30 days following receipt of the decision and of the assessment report referred to in paragraph 2, the relevant authorities shall recognise the decision and inform the competent authority of the reference Member State accordingly.

If, within the period referred to in the first subparagraph, a relevant authority has not expressed its disagreement in accordance with Article 13, the decision shall be deemed recognised by that relevant authority.

5.   Where the decision referred to in paragraph 2 has been recognised by all relevant authorities in accordance with paragraph 4, the measures provided for in Article 11 shall be taken.

1.   Where reference is made to this Article, the competent authority of the reference Member State shall take the following measures:

2.   Where reference is made to this Article, each relevant authority shall, where necessary and within the time limit laid down in paragraph 1 of Article 23, amend the decision granting the marketing authorisation in accordance with the accepted variation.

1.   By way of derogation from Article 10, 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 simultaneously to all relevant authorities an application containing the elements listed in Annex IV.

If the application fulfils the requirements laid down in the first subparagraph, the competent authority of the reference Member State shall acknowledge receipt of a valid application and inform the holder and the other relevant authorities that the procedure starts from the date of such acknowledgement.

3.   Within 30 days following the acknowledgement of receipt of a valid application, the competent authority of the reference Member State shall prepare an assessment report and a decision on the application, which shall be communicated to the other relevant authorities.

4.   Within the period referred to in paragraph 3, the competent authority of the reference Member State may request the holder to provide supplementary information. It shall inform the other relevant authorities accordingly.

5.   Within 12 days from the date of receipt of the decision and of the assessment report referred to in paragraph 3, the relevant authorities shall recognise the decision and inform the competent authority of the reference Member State accordingly.

6.   Where requested by the competent authority of the reference Member State, the clinical data and data concerning the stability of the medicinal product shall be submitted by the holder to all relevant authorities within 12 days from the expiry of the period referred to in paragraph 5.

The competent authority of the reference Member State shall evaluate the data referred to in the first subparagraph and draft a final decision within seven days following receipt of the data. The other relevant authorities shall, within seven days following its receipt, recognise that final decision and adopt a decision in accordance with the final decision.

1.   Where recognition of a decision in accordance with Article 10(4) or approval of an opinion in accordance with point (b) of Article 20(8) is not possible on grounds of a potential serious risk to public health in the case of medicinal products for human use or, in the case of veterinary medicinal products, on grounds of a potential serious risk to human or animal health or to the environment, a relevant authority shall request that the matter of disagreement be forthwith referred to the coordination group.

The party in disagreement shall give a detailed statement of the reasons for its position to all Member States concerned and to the applicant.

2.   Article 33(3), (4) and (5) of Directive 2001/82/EC or Article 29(3), (4) and (5) of Directive 2001/83/EC shall apply to the matter of disagreement referred to in paragraph 1.

1.   Where a minor variation of type IA is made, the holder shall submit to the Agency a notification containing the elements listed in Annex IV. This notification shall be submitted within 12 months following 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 17 shall be taken.

1.   The holder shall submit to the Agency a notification containing the elements listed in Annex IV.

If the notification fulfils the requirement laid down in the first subparagraph, the Agency shall acknowledge receipt of a valid notification.

2.   If within 30 days following the acknowledgement of receipt of a valid notification the Agency has not sent the holder an unfavourable opinion, its opinion shall be deemed favourable.

Where the opinion of the Agency on the notification is favourable, the measures provided for in Article 17 shall be taken.

3.   Where the Agency 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 of receipt of the unfavourable opinion, the holder may submit to the Agency 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 and the measures provided for in Article 17 shall be taken.

4.   Where an amended notification has been submitted, the Agency shall assess it within 30 days following its receipt and the measures provided for in Article 17 shall be taken.

1.   The holder shall submit to the Agency an application containing the elements listed in Annex IV.

If the application fulfils the requirements laid down in the first subparagraph, the Agency shall acknowledge receipt of a valid application.

2.   The Agency shall issue an opinion on the valid application referred to in paragraph 1 within 60 days following its receipt.

The Agency 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.

The period referred to in the first subparagraph shall be 90 days for variations listed in Part 2 of Annex V.

3.   Within the period referred to in paragraph 2, the Agency may request the holder to provide supplementary information within a time limit set by the Agency. The procedure shall be suspended until such time as the supplementary information has been provided. In this case the Agency may extend the period referred to in paragraph 2.

4.   Article 9(1) and (2) and Article 34(1) and (2) of Regulation (EC) No 726/2004 shall apply to the opinion on the valid application.

Within 15 days from the adoption of the final opinion on the valid application, the measures provided for in Article 17 shall be taken.

1.   Where reference is made to this Article, the Agency shall take the following measures:

2.   Where reference is made to this Article, the Commission shall, where necessary, based on a proposal from the Agency and within the time limit laid down in paragraph 1 of Article 23, amend the decision granting the marketing authorisation and update the Community Register of Medicinal Products provided for in Article 13(1) and Article 38(1) of Regulation (EC) No 726/2004 accordingly.

1.   By way of derogation from Article 16, the procedure laid down in paragraphs 2 to 7 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 Agency an application containing the elements listed in Annex IV.

If the application fulfils the requirements laid down in the first subparagraph, the Agency shall acknowledge receipt of a valid application and inform the holder that the procedure starts from the date of such acknowledgement.

3.   Within 45 days following the acknowledgement of receipt of a valid application, the Agency shall give its opinion on the application.

4.   Within the period referred to in paragraph 3, the Agency may request the holder to provide supplementary information.

5.   The Agency shall submit forthwith its opinion to the Commission.

The Commission shall, where necessary and on the basis of that opinion, adopt a decision on the variation to the terms of the marketing authorisation and inform the holder accordingly.

6.   Where requested, the holder shall submit the clinical data and the data concerning the stability of the medicinal product to the Agency within 12 days from the expiry of the period referred to in paragraph 3.

The Agency shall evaluate the data referred to in the first subparagraph and shall give its final opinion within 10 days following receipt of the data. The Agency shall communicate its final opinion to the Commission and to the holder within three days from the date of issue of its final opinion.

7.   Where necessary and based on the final opinion of the Agency, the Commission shall amend the decision granting the marketing authorisation and update the Community Register of Medicinal Products provided for in Article 13(1) of Regulation (EC) No 726/2004 accordingly.

1.   Regulations (EC) No 1084/2003 and (EC) No 1085/2003 are hereby repealed.

References to the repealed Regulations shall be construed as references to this Regulation.

2.   By way of derogation from paragraph 1, Regulations (EC) Nos 1084/2003 and 1085/2003 shall continue to apply to valid notifications or applications for variations which are pending at the date referred to in the second subparagraph of Article 28.