MultiHance - referral

Current status

European Commission final decision

Overview

MultiHance is a paramagnetic contrast agent for use in diagnostic magnetic resonance imaging (MRI), containing the active substance gadobenic acid 334 mg/ml, as the dimeglumine salt. The indication when first authorised in a number of Member States related to imaging of the liver, for the detection of focal liver lesions in patients with known or suspected primary liver cancer (e.g. hepatocellular carcinoma) or metastatic disease.

In November 1998, Bracco s.p.a. submitted applications for a Type II variation in the Mutual Recognition procedure, with the United Kingdom as Reference Member State, for MultiHance. The scope of the variation was to extend the indication to include MRI imaging of the CNS, in addition to the liver. The Mutual Recognition Variation procedure started on 8 December 1998. The Concerned Member States were Austria, Belgium, Denmark, Germany, Finland, Greece, France, Ireland, Italy, Luxembourg, The Netherlands and Sweden. The Concerned Member State, France, not agreeing to the conclusions and proposals in the Reference Member State's final variation assessment report referred the reasons for disagreement to the EMEA on 5 October 1999, with a request to initiate an arbitration procedure in order to clarify the matter.

The objections raised by France related to the main Phase III trials designed to show non-inferiority of MultiHance to an authorised comparator product. In summary, the referral notification stated that it was not possible to conclude non-inferiority of MultiHance to the comparator product in the main Phase III trials, mainly due to a major problem of external validity of the comparator, and to methodological biases. The CPMP prepared a list of questions for the Marketing Authorisation Holder, including the above issues, and the arbitration procedure started on 21 October 1999. The Applicant's response to this list of questions was received in February 2000 and the CPMP started the clock on 18 February 2000.

The CPMP having considered the written responses provided by the Applicant, the joint Rapporteur/Co- Rapporteur's assessment report, an oral explanation by the Marketing Authorisation Holder and the comments from CPMP members was of the opinion that the objections raised by France should not prevent the approval of the variation applied for.

The CPMP therefore adopted a positive opinion on 25 May 2000 CPMP recommending the granting of the variation of the Marketing Authorisation for MultiHance, and the amendment of the Summary of Product Characteristics.

An overall summary of the scientific evaluation is provided, together with the amended SPC.

A Decision was issued by the European Commission on 15 September 2000.

Opinion following a referral for arbitration according to Article 7(5) of Commission Regulation (EC) No 541/95 as amended, for MultiHance International Non-Proprietary Name (INN): gadobenic acid: Background information

Adopted Reference Number: CPMP/1361/00

Key facts

About this medicine

• Approved name:
  MultiHance
• International non-proprietary name (INN) or common name:
  gadobenic acid

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CPMP/1361/00
• Type:
  Article 6(12) referrals (prior to January 2010)

  This type of referral was triggered for a medicine that had been authorised by mutual recognition or via the decentralised procedure when there was disagreement between Member States on a variation (type II). This referral has been replaced by Article 13 referrals.

Key dates and outcomes

• CHMP opinion date:
  25/05/2000
• EC decision date:
  15/09/2000

All documents

Opinion following a referral for arbitration according to Article 7(5) of Commission Regulation (EC) No 541/95 as amended, for MultiHance International Non-Proprietary Name (INN): gadobenic acid: Background information

Adopted Reference Number: CPMP/1361/00

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.