Isotretinoin - referral

Current status

European Commission final decision

Overview

The European Medicines Agency has completed an arbitration procedure following a disagreement among Member States of the European Union (EU) regarding the authorisation of the generic isotretinoin-containing medicine from Ranbaxy (UK) Limited. The Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that the benefits of this medicine do not outweigh its risks, and the marketing authorisation granted in the United Kingdom cannot be recognised in other Member States of the EU: France and Spain. The marketing authorisation in the United Kingdom should also be suspended.

What is Isotretinoin?

Isotretinoin is a retinoid (a substance derived from vitamin A) that is used to treat severe acne that has not responded to standard treatments.

Acne is a skin disease caused by an excessive production of sebum (the skin's natural oil) from overactive sebaceous glands in the skin. The sebum accumulates under the skin and causes inflammation. Isotretinoin works by decreasing the size and activity of the sebaceous glands in the skin, reducing sebum production and inflammation in the skin.

Isotretinoin capsules from Ranbaxy are a generic medicine based on a 'reference medicine', Roaccutane, which has been marketed in the EU since 1984.

Why was Isotretinoin reviewed?

Ranbaxy (UK) Limited submitted the generic isotretinoin-containing medicine for mutual recognition on the basis of the initial authorisation granted by the United Kingdom (the 'reference Member State') on 20 November 2006. The company wanted the authorisation to be recognised in France and Spain (the 'concerned Member States').

However, the Member States were not able to reach an agreement and the United Kingdom referred the matter to the CHMP for arbitration on 29 July 2010.

The grounds for the referral were that the bioequivalence study to show that Ranbaxy's isotretinoin capsules produce the same levels of active substance in the body as Roaccutane had been performed under fasting conditions. As the product information states that the capsules should be taken with food, Spain considered that a bioequivalence study under fed conditions would be required for the granting of the marketing authorisation.

What are the conclusions of the CHMP?

The CHMP considered that demonstration of bioequivalence in the fed state was essential and in line with current guidance on investigation of bioequivalence. However, the company was unable to demonstrate bioequivalence under fed conditions.

Based on evaluation of the currently available data and the scientific discussion within the Committee, the CHMP concluded that bioequivalence of the generic isotretinoin capsules to the reference medicinal product has not been shown according to the current requirements. The CHMP therefore concluded that the benefits of the medicine do not outweigh its risks and recommended that the marketing authorisation should not be granted in the concerned Member States. In addition, the Committee recommended that the marketing authorisation for Isotretinoin Ranbaxy (UK) Limited in the United Kingdom be suspended until bioequivalence in the fed state is shown.

The European Commission issued a decision on 18 May 2011.

Questions and answers on Isotretinoin Ranbaxy (UK) Limited (isotretinoin 10 and 20 mg capsules)

Reference Number: EMA/820119/2010

Key facts

About this medicine

• Approved name:
  Isotretinoin
• International non-proprietary name (INN) or common name:
  isotretinoin

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29/001276
• 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.

Key dates and outcomes

• CHMP opinion date:
  16/12/2010
• EC decision date:
  18/05/2011

All documents

Isotretinoin - Article 29 referral - Assessment report

Adopted

Isotretinoin - Article 29 referral - Annex I

Adopted

Isotretinoin - Article 29 referral - Annex II

Adopted

Isotretinoin - Article 29 referral - Annex III

Adopted

Questions and answers on Isotretinoin Ranbaxy (UK) Limited (isotretinoin 10 and 20 mg capsules)

Reference Number: EMA/820119/2010

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.