Alkem - referral

Current status

European Commission final decision

Overview

On 23 June 2016, the European Medicines Agency (EMA) recommended the suspension of a medicine (Riluzole Alkem), for which studies were conducted at the Alkem Laboratories Ltd site in Taloja, India, and has required companies to provide new data for another medicine before it can be authorised in the EU.

The recommendations followed a joint routine inspection by German and Dutch authorities in March 2015, which revealed misrepresentation of data during the conduct of two different trials performed in 2013 and 2014 at the Taloja site. The findings cast doubts on the quality management system in place at the site, and thus on the reliability of the data of bioequivalence studies conducted between March 2013 and March 2015.

EMA's Committee for Medicinal Products for Human Use (CHMP) noted that, although there is no evidence of harm or lack of effectiveness linked to the conduct of studies by Alkem Laboratories Ltd, the studies cannot be accepted in marketing authorisation applications in the EU. Therefore, the Committee recommended that medicines authorised or being evaluated on the basis of these studies should be suspended or refused authorisation, unless alternative data are available from other sources.
The specific recommendations of the CHMP are as follows:

• Riluzole Alkem, a medicine for amyotrophic lateral sclerosis (ALS) which has yet to be marketed in the EU, should now be suspended.
• Ibuprofen Orion, a painkiller currently under evaluation by national authorities, cannot be authorised on the basis of studies carried out at Alkem Laboratories Ltd. So far no alternative studies from other sources have been provided
• Cefuroxime Ingen Pharma, currently under evaluation by national authorities, can still be considered for authorisation, as studies from other sources have been provided.
• Cefuroxime Alkem and Cefuroxime Krka (antibiotics) can remain on the market in the EU, as alternative studies have been provided that support a positive benefit-risk balance.

The CHMP's recommendations concerning these medicines were sent to the European Commission, which issued a legally binding decision valid throughout the EU.

EMA will continue to work closely with national authorities and international partners to ensure that studies underpinning marketing authorisations in the EU are carried out to the highest standards and that companies continue to comply fully with all aspects of Good Clinical Practice (GCP).

Information for patients and for healthcare professionals

Some studies carried out at the Alkem Laboratories Ltd site have been found to be flawed. As a result, a medicine is being suspended. Medicines under evaluation cannot be granted authorisation on the basis of these studies; further data would have to be provided to support authorisation.

• The medicine being suspended, Riluzole Alkem, contains riluzole and is not yet on the market in the EU. Its suspension is therefore not expected to have any impact on patients in the EU. Other riluzole-containing medicines remain available.
• There is no evidence of harm or lack of effectiveness with any of the medicines linked to studies conducted by Alkem Laboratories Ltd.
• Patients should continue to take their medicines as prescribed.

More about the medicines

The review covered medicines authorised via national procedures in individual EU Member States, whose marketing authorisation applications included data from studies conducted by Alkem Laboratories Ltd, Department of Bioequivalence, C-17/7, MIDC Industrial Estate, Taloja, Dist. Raigad - 410208 India. It also included ongoing marketing authorisation applications for medicines which use study data from the site.

More about the procedure

The review of Alkem was initiated on 1 April 2016 at the request of the German medicines authority (BfArM), under Article 31 of Directive 2001/83/EC.

The review was carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which has adopted the Agency's opinion. The CHMP opinion was forwarded to the European Commission, which issued a final legally binding decision applicable in all EU Member States on 8 September 2016.

Alkem Article-31 referral - Studies from Alkem Laboratories Ltd cannot be used to support medicines approval in the EU

Reference Number: EMA/427636/2016 Rev. 1

Key facts

About this medicine

• Approved name:
  Alkem

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-31/1436
• Type:
  Article 31 referrals

  This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Key dates and outcomes

• CHMP opinion date:
  23/06/2016
• EC decision date:
  08/09/2016

All documents

Procedure started

Alkem Article-31 referral - Annex I

Reference Number: EMA/239593/2016 Rev. 1

Alkem Article-31 referral - Review started

Reference Number: EMA/186742/2016

Alkem Article-31 referral - CHMP List of questions to Alkem BE Centre

Reference Number: EMA/CHMP/228248/2016

Alkem Article-31 referral - CHMP list of questions

Reference Number: EMA/CHMP/228189/2016

Alkem Article-31 referral - Timetable for the procedure

Reference Number: EMA/CHMP/228190/2016

Alkem Article-31 referral - Notification

Opinion provided by Committee for Medicinal Products for human Use

Alkem Article-31 referral - Studies from Alkem Laboratories Ltd cannot be used to support medicines approval in the EU

Reference Number: EMA/427636/2016 Rev. 1

European Commission final decision

Alkem Article-31 referral - Assessment report

AdoptedReference Number: EMA/630996/2016

Alkem Article-31 referral - Annex II

Alkem Article-31 referral - Annex III

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.