Paclitaxel Hetero and associated names - referral

Current status

European Commission final decision

Overview

On 18 October 2018, the European Medicines Agency (EMA) completed a review of Paclitaxel Hetero following a disagreement among EU Member States regarding its authorisation. The Agency concluded that the benefits of Paclitaxel Hetero do not outweigh its risks, and the marketing authorisation cannot be granted in Portugal or in other Member States of the EU (Germany, the Netherlands and the UK).

What is Paclitaxel Hetero?

Paclitaxel Hetero is a medicine that contains the active substance paclitaxel. It was to be available as a concentrate for solution for infusion (6 mg/ml) for the treatment of breast cancer, cancer of the ovaries, non-small cell lung cancer and Kaposi’s sarcoma (a cancer of the blood vessels) in patients with acquired immune deficiency syndrome (AIDS).

Paclitaxel belongs to the group of cancer medicines known as the ‘taxanes’. It blocks the ability of cancer cells to break down their internal ‘skeleton’ that allows them to divide and multiply. With their skeleton still in place, the cells cannot divide and they eventually die.

Paclitaxel Hetero was developed as a generic medicine. This means that Paclitaxel Hetero was developed to contain the same active substance and work in the same way as a ‘reference medicine’ already authorised in EU called Taxol.

The paclitaxel in Paclitaxel Hetero and in Taxol is contained in tiny particles called micelles, to help it dissolve in the solution.

Why was Paclitaxel Hetero reviewed?

Hetero Europe S.L. Viladecans (Barcelona) submitted Paclitaxel Hetero to the Portuguese medicines agency for a decentralised procedure. This is a procedure where one Member State (the ‘reference Member State’, in this instance Portugal) 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 where the company has applied for a marketing authorisation (the ‘concerned Member States’, in this instance Germany, the Netherlands and the UK).

However, the Member States were not able to reach an agreement and the Portuguese agency referred the matter to EMA for arbitration on 2 November 2017.

The grounds for the referral were concerns raised by the Netherlands that the data submitted to support the application were not sufficient to show that Paclitaxel Hetero is ‘bioequivalent’ to Taxol. Two medicines are bioequivalent when they produce the same levels of the active substance in the body and are therefore expected to have the same effect. In particular, the company did not provide direct comparative data with the reference medicine, which is normally required for medicines formulated in micelles. Instead, it submitted indirect comparative data and a study which compared blood levels of paclitaxel in Paclitaxel Hetero with those of another generic paclitaxel medicine, which was not considered sufficient by the Netherlands.

What is the outcome of the review?

Based on the evaluation of the currently available data, the Agency concluded that they were not sufficient to show that Paclitaxel Hetero is ‘bioequivalent’ to Taxol and that their active substances behave in the same way in the body.

The Agency therefore concluded that the benefits of Paclitaxel Hetero do not outweigh its risks and recommended that the marketing authorisation should not be granted in the concerned Member States.

More about the procedure

The review of Paclitaxel Hetero was initiated at the request of Portugal under Article 29 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 11 January 2019.

Paclitaxel Hetero Article 29(4) referral - EMA recommends refusal of authorisation for Paclitaxel Hetero (paclitaxel, 6 mg/ml concentrate for solution for infusion)

Reference Number: EMA/712446/2018 Summary:

EMA completes review following disagreement among EU Member States

Key facts

About this medicine

• Approved name:
  Paclitaxel Hetero and associated names
• International non-proprietary name (INN) or common name:
  paclitaxel

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-29(4)/1466
• 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:
  18/10/2018
• EC decision date:
  11/01/2019

All documents

Opinion provided by Committee for Medicinal Products for human Use

Paclitaxel Hetero Article 29(4) referral - EMA recommends refusal of authorisation for Paclitaxel Hetero (paclitaxel, 6 mg/ml concentrate for solution for infusion)

Reference Number: EMA/712446/2018 Summary:

EMA completes review following disagreement among EU Member States

European Commission final decision

Paclitaxel Hetero and associated names Article 29(4) referral - Assessment report

Adopted Reference Number: EMA/813213/2018

Paclitaxel Hetero and associated names ARticle 29(4) referral - Annex II

Adopted

Paclitaxel Hetero and associated names ARticle 29(4) referral - Annex I

Adopted

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.