Methylphenidate Sandoz - referral

Current status

European Commission final decision

Overview

On 25 July 2013, the European Medicines Agency completed an arbitration procedure following a disagreement among Member States of the European Union (EU) regarding the authorisation of the medicine Methylphenidate Sandoz. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of Methylphenidate Sandoz outweigh its risks, and the marketing authorisation granted in Denmark can be recognised in other Member States of the EU.

What is Methylphenidate Sandoz?

Methylphenidate is a medicine that is used to treat children aged between 6 and 18 years of age who have attention-deficit / hyperactivity disorder (ADHD), a condition in which children show a persistent inability to concentrate, hyperactivity and impulsive behaviour.

Methylphenidate belongs to a group of medicines called 'psychostimulants' and is thought to work by enhancing the activity of areas of the brain that control attention and concentration. It has been available since the 1950s as both immediate-release tablets and capsules, which release methylphenidate straight away, and as modified-release tablets that release some or all of the active substance more slowly over several hours.

Methylphenidate Sandoz is a generic medicine based on a 'reference medicine', Concerta, which is authorised in all the EU Member States. It is available as a modified-release tablet, which releases some of the active substance immediately (the 'immediate-release phase') and the rest over several hours.

Why was Methylphenidate Sandoz reviewed?

Sandoz A/S submitted Methylphenidate Sandoz for mutual recognition on the basis of the initial authorisation granted by Denmark on 29 March 2012 and also valid through a decentralised procedure in Cyprus, Finland, Poland, Portugal and Spain, as well as Iceland and Norway. The company wanted the authorisation to be recognised in Belgium, France, Germany, Luxembourg, Malta, Netherlands, Sweden and United Kingdom (the 'concerned Member States').

However, the Member States were not able to reach an agreement and the Danish medicines regulatory agency referred the matter to the CHMP for arbitration on 21 December 2012.

The grounds for the referral were objections raised by Germany and the Netherlands, which considered that the bioequivalence study carried out under fed conditions did not show that Methylphenidate Sandoz was bioequivalent for the immediate-release phase to its reference product. As the product information states that the tablet can be taken with or without food, a bioequivalence study in fed conditions was required to grant the marketing authorisation. Two medicines are bioequivalent if they produce the same levels of the active substance in the body.

What are the conclusions of the CHMP?

Based on evaluation of the currently available data and the scientific discussion within the Committee, the CHMP concluded that the failure to show bioequivalence between Methylphenidate Sandoz and its reference medicine in the immediate-release phase under fed conditions were due to differences between patients in the effects of a high-fat meal on the way medicines are handled by the body, and not to differences between the formulations of the two medicinal products, and that bioequivalence to the reference medicinal product has been shown. The Committee also noted that the studies were performed by the applicant before the publication of recent updated guidance* for products of this type. The CHMP therefore concluded that the benefits of Methylphenidate Sandoz outweigh its risks and recommended that the marketing authorisation be granted in the concerned Member States.

The European Commission issued a decision on this opinion on 09 October 2013.

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*Committee for Human Medicinal Products. Questions & Answers: Positions on specific questions addressed to the pharmacokinetics working party. 11. Requirements for demonstration of bioequivalence for generics of biphasic modified release formulations for oral use. EMA/618604/2008 Rev. 7.

Methylphenidate Sandoz Article-29 referral - Questions and answers on Methylphenidate Sandoz (methylphenidate hydrochloride, prolonged-release tablet, 18, 36 and 54 mg)

Reference Number: EMA/444197/2013

Key facts

About this medicine

• Approved name:
  Methylphenidate Sandoz
• International non-proprietary name (INN) or common name:
  methylphenidate hydrochloride
• Class:
  -

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29/1359
• 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:
  25/07/2013
• EC decision date:
  09/10/2013

All documents

Opinion provided by Committee for Medicinal Products for human Use

Methylphenidate Sandoz Article-29 referral - Questions and answers on Methylphenidate Sandoz (methylphenidate hydrochloride, prolonged-release tablet, 18, 36 and 54 mg)

Reference Number: EMA/444197/2013

European Commission final decision

Methylphenidate Sandoz Article-29 referral - Annex I

Methylphenidate Sandoz Article-29 referral - Annex II

Methylphenidate Sandoz Article-29 referral - Annex III

Methylphenidate Sandoz Article-29 referral - Assessment report

Adopted Reference Number: EMA/596774/2013

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.