- Procedure started
- Under evaluation
- CHMP opinion
- European Commission final decision
Table of contents
Gadovist/Gadograf 1.0 mmol/ml contains gadobutrol, a neutral macrocyclic gadolinium (Gd) complex with contrast-enhancing properties, which is used for magnetic resonance imaging (MRI). MRI is a widely used technique for the evaluation and detection of diffuse liver disease as well as for further characterisation of focal liver disease. Gd-based contrast agents are frequently administered prior to contrast-enhanced dynamic liver MRI and may improve both detection and classification of focal liver lesions.
Gadovist/Gadograf was approved for "Contrast enhancement in cranial and spinal magnetic resonance imaging" in Germany in January 2000 and subsequently in June 2000 in the EU and Norway via the mutual recognition procedure (MRP). A label extension to the indication "Contrast-enhanced Magnetic resonance angiography" (CE-MRA) followed in November 2003.
In June 2005, a MR procedure started for a type II variation to add the indication of "Contrast enhanced MRI of other body regions: liver, kidneys" and the following posology and method of administration/dosage: "CE-MRI of other body regions: The recommended dose for adults is 0.1 mmol per kilogram body weight (mmol/kg BW). This is equivalent to 0.1 ml/kg BW of the 1.0 M solution". After finalisation of the procedure the Spanish Agency for Medicines and Health Products initiated a referral for arbitration to the CHMP under article 36.1 of Directive 2001/83/EC.
Having considered the grounds for the referral triggered by Spain, the CHMP, during its May 2006 plenary meeting, adopted a List of Questions and a TT for a referral procedure under Article 36. The CHMP appointed Dr. Broich (DE) as Rapporteur and Dr. Prieto (ES) as Co- Rapporteur.
The questions identified pertained to insufficient data on the evaluation of disseminated liver disease that could justify an extrapolation to the general population undergoing examinations of liver and kidney. Concerns were further raised with regards to the Paediatric Indication and the use of the comparator Magnevist. Magnevist is not approved "to classify focal lesions [of liver or kidney] as benign or malignant" throughout the EU and it was questioned whether it would support the granting of an indication for which Magnevist has not been approved. The Applicant was asked to justify the choice of this comparator and the clinical utility of Gadovist/Gadograf with respect to diagnostic thinking, therapeutic management and clinical outcome. A Request for Supplementary Information was adopted on 16 November 2006. The company responded to these points on 30 November 2006. In its response the Applicant addressed the issue of clinical utility by comparing Gadovist-enhanced with Magnevistenhanced MRI and underlined the diagnostic efficacy of Gadovist/Gadograf. The Applicant further agreed to the proposed wording by the CHMP as follows:
Section 4.1 (Indication):
"Contrast enhanced MRI of liver or kidneys in patients with high suspicion or evidence of having focal lesions to classify these lesions as benign or malignant". Section 4.2 (Posology):
Gadograf is not recommended for use in population below age 18 due to a lack of data on efficacy and safety."
The CHMP opinion was converted into a Decision by the European Commission on 13 April 2007.
The list of product names concerned is given in Annex I. The scientific conclusions are provided in Annex II and the amended Summary of Product Characteristics in Annex III.
About this medicine
|International non-proprietary name (INN) or common name||
About this procedure
European Commission final decision
Article 36 referrals (prior to July 2012)
This type of referral applied for a marketing authorisation that were granted via the mutual-recognition or decentralised procedure. It was triggered when a Member State considered that action (variation, suspension or withdrawal) was needed on the grounds of the need to protect public health. This referral has been replaced by Articles 107i and 31.
Key dates and outcomes
|CHMP opinion date||
|EC decision date||
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.