Rambis and associated names - referral

Current status

European Commission final decision

Overview

EMA recommends authorisation of Rambis (ramipril / bisoprolol) in the EU

On 15 December 2022, the European Medicines Agency completed a review of Rambis following a disagreement among EU Member States regarding its authorisation. The Agency concluded that the benefits of Rambis outweigh its risks, and marketing authorisation should be granted in Poland and in the other Member States of the EU where the company has applied for a marketing authorisation (Czechia and Slovakia).

What is Rambis?

Rambis is a medicine for patients with certain long-term heart conditions and high blood pressure in whom these conditions are well controlled by a combination of two medicines called ramipril and bisoprolol.

Rambis contains both ramipril and bisoprolol and is intended as a replacement for patients taking these medicines separately. Patients taking Rambis will have ramipril and bisoprolol at the same dose and schedule as before.

Why was Rambis reviewed?

Adamed Pharma S.A. submitted a marketing authorisation application for Rambis to the Polish medicines regulatory agency for evaluation under a decentralised procedure. This is a procedure where one Member State (the ‘reference Member State’, in this instance Poland) assesses a medicine with a view to granting a marketing authorisation that will be valid in this country as well as in other Member States (the ‘concerned Member States’, in this instance Czechia and Slovakia) where the company has applied for a marketing authorisation.

However, the Member States were not able to reach an agreement and the Polish medicines regulatory agency referred the matter to EMA for arbitration on 22 June 2022.

The grounds for the referral were concerns from the medicines agency in Czechia that the company had not complied with the relevant guideline for combination medicines. The parts of the guideline at issue were those requiring the company to show how each of the active substances contributes to the medicine’s overall effects and to show that the benefits of the combination outweigh the risks for all strengths and uses.

What is the outcome of the review?

Based on the evaluation of all the available data, the Agency concluded that there is sufficient evidence to support the use of the ramipril and bisoprolol combination. Furthermore, having both substances in the same medicine will benefit patients who need them.

The Agency therefore concluded that the benefits of Rambis outweigh its risk and recommended that marketing authorisation be granted in all concerned Member States.

More about the procedure

The review of Rambis was initiated on 22 June 2022 at the request of Poland under Article 29(4) of Directive 2001/83/EC.

The review was carried out by EMA’s Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use.

The European Commission issued an EU-wide legally binding decision on the marketing authorisation of Rambis on 15 February 2023.

Rambis Article 29(4) referral - EMA recommends authorisation of Rambis (ramipril / bisoprolol) in the EU

Reference Number: EMA/75435/2023

Key facts

About this medicine

• Approved name:
  Rambis and associated names
• International non-proprietary name (INN) or common name:
  • ramipril
  • bisoprolol fumarate
• Associated names:
  Ralbior

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29(4)/1519
• Type:
  Article 29(4) referrals

  This type of referral is triggered when there is a disagreement between Member States regarding a marketing authorisation application being evaluated in a mutual-recognition or decentralised procedure, on the grounds of a potential serious risk to public health.

• Authorisation model:
  Nationally authorised product(s)
• Decision making model:
  CHMP-EC

Key dates and outcomes

• CHMP opinion date:
  15/12/2022
• EC decision date:
  15/02/2023

All documents

Opinion provided by Committee for Medicinal Products for human Use

Rambis Article 29(4) referral - Annex III

European Commission final decision

Rambis Article 29(4) referral - Assessment report

Adopted Reference Number: EMA/15850/2023

Rambis Article 29(4) referral - Annex III

Rambis Article 29(4) referral - Annex II

Rambis Article 29(4) referral - Annex I

Rambis Article 29(4) referral - EMA recommends authorisation of Rambis (ramipril / bisoprolol) in the EU

Reference Number: EMA/75435/2023

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.