COMMISSION REGULATION (EC) No 542/95 of 10 March 1995 concerning the examination of variations to the terms of a marketing authorization falling within the scope of Council Regulation (EEC) No 2309/93
THE COMMISSION OF THE EUROPEAN  COMMUNITIES
,
Having regard to the Treaty establishing the European Community,
Having regard to Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of  Medicinal Products (1), and in particular Articles 15 (4) and 37 (4) thereof,
Whereas, appropriate provisions should be adopted for the examination of variations to the terms of a marketing authorization of medicinal products which have been authorized in accordance with Regulation (EEC) No 2309/93;
Whereas, it is appropriate to include a notification system or administrative procedures concernng minor variations for which it is necessary to precisely define minor variations;
Whereas, moreover, it is necessary to distinguish from amongst those variations which do not qualify as minor variations, those which must be considered to so fundamentally alter the marketing authorization, particularly form the point of view of the  quality, safety or efficacy of a medicinal product, that a new application for a marketing authorization would be required;
Whereas, the provisions of this Regulation are in accordance with the opinion of the Standing Committee on Medicinal Products for Human Use and the Standing Committee on Veterinary Medicinal Products,
Scope and definitions
1. This Regulation lays down the procedure for the examination of applications for variations to the terms of a marketing authorization granted in accordance with Regulation (EEC) No 2309/93.
2. This Regulation does not impede the marketing authorization holder from taking provisional urgent safety restrictions in the event of risk to public or animal health. The holder shall forthwith inform the Agency. If the Agency has not raised any  objections within 24 hours, the urgent safety restrictions may be introduced and the corresponding application for this variation shall be submitted without delay to the Agency for the application of the procedures set out in Articles 6 and 7 of this  Regulation.
For the purpose of this Regulation, the following definitions shall apply;
1. 'variation to the terms of a marketing authorization': an amendment to the contents of the documents referred to in Article 6 (1) and (2) or Article 28 (1) and (2) of Regulation (EEC) No 2309/93 such as they existed at the moment the decision on the  marketing authorization has been adopted in accordance with Article 10 or Article 32 of that Regulation or after approval of any previous variations, except where a new application for a marketing authorization must be presented pursuant to Annex II to  this Regulation.
2. 'Urgent safety restriction': an interim change to product information by the marketing authorization holder restricting the indication(s), and/or dosage, and/or target species of the medicinal product; or adding a contra-indication, and/or warning  due to new information having a bearing on the safe use of the product.
1. (a) A 'minor variation' (type I) means a variation as defined in Article 2 and listed in Annex I to this Regulation, provided the conditions for such variation laid down in the said Annex are met.
(b) A 'major variation' (type II) means a variation as defined in Article 2 which cannot be deemed to be a type I variation within the meaning of the preceding paragraph.
2. For the purposes of this Regulation, transfer of marketing authorization to a new holder, except for the situations covered by the point 3 of Annex I to this Regulation, and changes to the maximum residue limit (MRL) shall not be considered as a  variation in the meaning of Article 2 (1).
Notification procedure for minor variations
1. To obtain a type I variation, the holder of the marketing authorization shall submit to the Agency an application, accompanied by documents demonstrating that the conditions laid down in Annex I to this Regulation for the requested  variation are met, and all documents amended as a result of the application.
2. An application within the meaning of paragraph 1 shall not concern more than one variation in the marketing authorization. Where several variations are to be made to a single marketing authorization, an application shall be submitted within the  meaning of paragraph 1 in respect of each variation sought; each such application shall contain a reference to the other application(s).
3. By derogation from paragraph 2, where a variation in the marketing authorization entails one or more further changes, a single application may cover all such consequential variations. The single application shall describe the relation between the  main variation and its consequential variations.
4. To be valid an application within the meaning of paragraph 1 shall be consistent with the provisions of this Article and accompanied by the relevant fee provided for in the applicable Community regulation.
1. If, within 30 days of receipt of a valid application as provided for in Article 4, the Agency has not sent the holder of the marketing authorization the notification provided for in paragraph 4, the variation applied for shall be deemed to  have been accepted.
2. The Agency shall inform the Commission within the period referred to in the preceding paragraph of the variation to be made to the terms of the marketing authorization. The Commission shall, where necessary, amend the decision taken pursuant to
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or Article 32 of Regulation (EEC) No 2309/93. The decision thus amended shall take effect retroactively from the day following the end of the period referred to in paragraph 1.
3. The Community Register of Medicinal Products provided for in Articles 12 and 34 of Regulation (EEC) No 2309/93 shall be updated as necessary.
4. Where the Agency is of the opinion that the application cannot be accepted, it shall send a notification to that effect to the holder of the marketing authorization within the period referred to in paragraph 1, stating the objective grounds on which  its opinion is based:
(a) within 30 days of receipt of the said notification, the marketing authorization holder may amend the application in a way which takes due account of the grounds set out in the notification. In that case the provisions of paragraphs 1, 2 and 3 shall  apply to the amended application.
(b) if the marketing authorization holder does not amend the application as provided for in (a) above, this application shall be deemed to have been rejected.
Approval procedure for major variations
1. To obtain a type II variation, the holder of the marketing authorization shall send the Agency an application accompanied by the relevant particulars and supporting documents referred to in Article 2 (1) of this Regulation.
The application must also be accompanied by:
- the supporting data relating to the variation applied for,
- all documents amended as a result of the application,
- an Addendum to or updating of existing expert report(s) to take account of the variation applied for.
2. An application within the meaning of paragraph 1 shall not concern more than one variation in the marketing authorization. Where several variations are to be made to a single marketing authorization, an application shall be submitted within the  meaning of paragraph 1 in respect of each variation sought; each such application shall contain a reference to the other application(s).
3. By derogation from paragraph 2, where a variation in the marketing authorization entails one or more further changes, a single application may cover all such consequential variations. The single application shall describe the relation between the  main variation and its consequential variations.
4. To be valid an application within the meaning of paragraph 1 shall be consistent with the provisions of this Article and accompanied by the relevant fee provided for in the applicable Community regulation.
1. The competent Committee of the Agency shall give its opinion within 60 days following receipt of a valid application as provided for in Article 6.
2. Within that period, the competent Committee may send the marketing authorization holder a single request for information supplementary to that already supplied pursuant to Article 6. In this case, the period shall be extended by a further 60 days.  This period may be extended, for a period to be determined by the competent Committee, on its own initiative or at the request of the marketing authorization holder.
1. Where the competent Committee delivers a favourable opinion, the Agency shall so inform the marketing authorization holder and the Commission forthwith and shall send to the Commission the amendments to be made to the terms of the  marketing authorization accompanied by the documents set out in Article 9 (3) and Article 31 (3) of Council Regulation (EEC) No 2309/93.
2. Where the competent Committee delivers an unfavourable opinion, the appeal procedure provided for in Article 9 (1) and (2) or Article 31 (1) and (2) of Regulation (EEC) No 2309/93 shall apply.
3. The decision varying the terms of the marketing authorization shall be adopted in accordance with the procedure laid down in Article 10 or Article 32 of Regulation (EEC) No 2309/93.
4. The Community Register of Medicinal Products provided for in Articles 12 and 34 of Regulation (EEC) No 2309/93 shall be updated as necessary.
This Regulation shall enter into force on the third day following its publication in the Official Journal of the European Communities.
This Regulation shall be binding in its entirety and directly applicable in all Member States.