Ibuprofen NVT - referral

Current status

European Commission final decision

Overview

EMA recommends refusal of authorisation for Ibuprofen NVT (ibuprofen, 400 mg, soft capsules)

On 22 February 2024, the European Medicines Agency (EMA) completed a review of Ibuprofen NVT 400 mg soft capsules following a disagreement among EU Member States regarding its authorisation. The Agency concluded that the benefits of Ibuprofen NVT 400 mg do not outweigh its risks and the marketing authorisation granted in Lithuania cannot be recognised in Spain, where the company had applied for a marketing authorisation.

In addition, the marketing authorisations in Lithuania and other Member States where the medicine is authorised (Estonia, France, Latvia, Poland and Romania) should be suspended.

What is Ibuprofen NVT?

Ibuprofen NVT is a painkiller and anti-inflammatory medicine that belongs to the class of medicines called non-steroidal anti-inflammatory drugs (NSAIDs).

The active substance in Ibuprofen NVT, ibuprofen, works by blocking an enzyme called cyclo-oxygenase, which produces prostaglandins, substances that are involved in the inflammation process. By reducing the production of prostaglandins, Ibuprofen NVT is expected to reduce fever and pain linked to inflammation.

Ibuprofen NVT is a generic medicine. This means that Ibuprofen NVT was developed to contain the same active substance and work in the same way as a ‘reference medicine’ already authorised in the EU. The reference medicine is Nurofen Rapid 400 mg soft capsules.

Why was Ibuprofen NVT reviewed?

The applicant, Laboratorios Liconsa S.A., requested that the marketing authorisation for Ibuprofen NVT 400 mg granted in Lithuania (the ‘reference Member State’) on 8 June 2022 be recognised in Spain (the ‘concerned Member State’).

However, the Member States were not able to reach an agreement and the Lithuanian medicines agency referred the matter to EMA for arbitration on 17 November 2023.

The grounds for the referral were concerns raised by the Spanish medicines agency, which considered that Ibuprofen NVT 400 mg was not bioequivalent to the reference medicine. Two medicines are considered bioequivalent if the active substances from both medicines are absorbed in the body at the same rate and to the same extent.

The Spanish agency had concerns about the average time it takes for the active substance to reach its maximum level (known as median T_max), as this measure was higher with Ibuprofen NVT 400 mg than with the reference medicine. Based on this, the Spanish agency had concerns that Ibuprofen NVT 400 mg may not have the same effect as the reference medicine. 

What is the outcome of the review?

For two medicines to be considered bioequivalent, all the bioequivalence criteria defined in EU guidance must be met. For Ibuprofen NVT 400 mg, the company submitted data from a bioequivalence study and data from scientific literature.

After reviewing the available data, EMA concluded that, although other bioequivalence criteria had been met, the median T_max for Ibuprofen NVT 400 mg was not comparable with that of the reference medicine. Therefore bioequivalence of Ibuprofen NVT 400 mg to the reference medicine had not been shown.

The Agency concluded that the benefits of Ibuprofen NVT 400 mg do not outweigh its risks and recommended that the marketing authorisation should not be granted in Spain. In addition, until all criteria for bioequivalence have been met, marketing authorisations for Ibuprofen NVT 400 mg in Lithuania, Estonia, France, Latvia, Poland and Romania should be suspended. 

More about the procedure

The review of Ibuprofen NVT 400 mg was initiated on 17 November 2023 at the request of Lithuania 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 Ibuprofen NVT on 10 May 2024.

EMA recommends refusal of authorisation for Ibuprofen NVT (ibuprofen, 400 mg, soft capsules)

AdoptedReference Number: EMA/231236/2024

Key facts

About this medicine

• Approved name:
  Ibuprofen NVT
• International non-proprietary name (INN) or common name:
  ibuprofen

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29(4)/1533
• 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)

Key dates and outcomes

• CHMP opinion date:
  22/02/2024
• EC decision date:
  13/05/2024

All documents

Opinion provided by Committee for Medicinal Products for human Use

EMA recommends refusal of authorisation for Ibuprofen NVT (ibuprofen, 400 mg, soft capsules)

AdoptedReference Number: EMA/231236/2024

European Commission final decision

Ibuprofen NVT Article 29(4) referral - Assessment report

AdoptedReference Number: EMA/16944/2024

Ibuprofen NVT Article 29(4) referral - Annex I

Adopted

Ibuprofen NVT Article 29(4) referral - Annex III

Ibuprofen NVT Article 29(4) referral - Annex II

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.