Micro Therapeutic Research - referral

Current status

European Commission final decision

Overview

EMA recommends suspension of medicines due to unreliable studies from Micro Therapeutic Research Labs

Medicines where suitable alternative data are available can remain on market

On 23 March 2017, the European Medicines Agency (EMA) recommended suspending a number of nationally approved medicines for which bioequivalence studies were conducted by Micro Therapeutic Research Labs at two sites in India. Bioequivalence studies are usually the basis for approval of generic medicines. The Micro Therapeutic Research Article-31 referral - Products for which the marketing authorisations are recommended for suspension and marketing authorisation applications which do not satisfy the criteria for authorisation... is available. The suspensions can be lifted once alternative data establishing bioequivalence are provided.

Alternative supporting data had already been provided for several of the medicines reviewed. Therefore, the Agency recommended that these medicines could remain on the market. The Micro Therapeutic Research Article-31 referral - Medicinal products recommended for maintenance and marketing authorisation applications for which bioequivalence vis-à -vis the EU reference medicinal product has been est... is available.

The Agency also recommended that medicines not yet authorised but which were being evaluated on the basis of bioequivalence studies from these sites should not be authorised until bioequivalence is demonstrated using alternative data.

Micro Therapeutic Research Labs is a contract research organisation (CRO) which conducts the analytical and clinical parts of bioequivalence studies, some of which are used to support marketing authorisation applications of medicines in the EU.

The review of medicines studied by Micro Therapeutic Research Labs was started after inspections to check compliance with good clinical practice (GCP) by Austrian and Dutch authorities in February 2016. The inspections identified several concerns at the company's sites regarding misrepresentation of study data and deficiencies in documentation and data handling.

The review, by EMA's Committee for Medicinal Products for Human Use (CHMP), concluded that data from studies conducted at the sites between June 2012 and June 2016 are unreliable and cannot be accepted as a basis for marketing authorisation in the EU. However, there is no evidence of harm or lack of effectiveness of medicines authorised and being evaluated in the EU on the basis of studies at the sites.

Some of the medicines which have been recommended for suspension may be of critical importance (e.g. due to lack of available alternatives) in certain EU Member States. Therefore national authorities can temporarily postpone the suspension in the interest of patients. Member States should also decide whether recalls of the affected medicines are needed in their territories.

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

Information for patients and healthcare professionals

• A number of medicines for use in the EU were approved based on studies carried out at two Micro Therapeutic Research Labs sites in India. The studies are unreliable because of problems in the way data and documents were managed at the sites. As a result, several medicines approved in the EU have been suspended.
• The Micro Therapeutic Research Article-31 referral - Products for which the marketing authorisations are recommended for suspension and marketing authorisation applications which do not satisfy the criteria for authorisation...
• There is currently no evidence of unexpected harm or lack of effectiveness with any medicine approved on the basis of studies conducted at Micro Therapeutic Research Labs.
• Several medicines which were approved on the basis of studies conducted at Micro Therapeutic Research Labs can remain on the market in the EU. This is because during this review, alternative data were provided for these medicines.
• The Micro Therapeutic Research Article-31 referral - Medicinal products recommended for maintenance and marketing authorisation applications for which bioequivalence vis-à -vis the EU reference medicinal product has been est....
• National authorities in the EU will consider how critical individual medicines recommended for suspension are in their countries and make final decisions on whether to suspend or allow them to remain available, while new data are generated.
• Patients should continue to take their medicines as prescribed and contact their doctors in case of questions or concerns.

More about the medicines

The review covered one medicine authorised centrally through EMA (Tadalafil Mylan), as well as medicines authorised by national procedures in EU Member States (including decentralised or mutual recognition procedures), whose marketing authorisation applications included data from studies conducted by Micro Therapeutic Research Labs at two sites in India:

• Micro Therapeutic Research Labs Pvt. Ltd Rajam Bhavanam, No. 6, Kamarajar Salai, Selaiyur, East Tambaram, Chennai-600 059, Tamil Nadu.
• Micro Therapeutic Research Labs, No. 29 A, Krishna Madhuravanam, Vellokinar Pirivu, Thudiyalur, Coimbatore-641 029, Tamil Nadu.

The review also included ongoing marketing authorisation applications for medicines which use study data from these sites.

More about the procedure

The review was initiated on 15 December 2016 by several medicines regulatory agencies – Austria, Bulgaria, Croatia, Denmark, Estonia, Finland, Germany, Hungary, Iceland, Latvia, the Netherlands, Norway, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom - 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 all questions concerning medicines for human use, which adopted its opinion. The CHMP opinion was forwarded to the European Commission, which issued a final legally binding decision applicable in all EU Member States on 23 June 2017.

Micro Therapeutic Research Article-31 referral - EMA recommends suspension of medicines due to unreliable studies from Micro Therapeutic Research Labs

AdoptedReference Number: EMA/188204/2017

Key facts

About this medicine

• Approved name:
  Micro Therapeutic Research
• Class:
  -

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-31/1450
• 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:
  23/03/2017
• EC decision date:
  23/06/2017

All documents

Procedure started

Micro Therapeutic Research Article-31 referral - Annex I

Reference Number: EMA/866024/2016 Rev. 3

Micro Therapeutic Research Article-31 referral - Review started

Reference Number: EMA/850878/2016

Micro Therapeutic Research Article-31 referral - CHMP list of questions to be addressed by Micro Therapeutic Research Labs

Reference Number: EMA/CHMP/302887/2016

Micro Therapeutic Research Article-31 referral - CHMP list of questions to be addressed by the applicants/marketing authorisation holders

Reference Number: EMA/CHMP/847556/2016

Micro Therapeutic Research Article-31 referral - Timetable for the procedure

Reference Number: EMA/CHMP/847557/2016

Micro Therapeutic Research Article-31 referral - Notification

Opinion provided by Committee for Medicinal Products for human Use

Micro Therapeutic Research Article-31 referral - Medicinal products recommended for maintenance and marketing authorisation applications for which bioequivalence vis-à -vis the EU reference medicinal product has been est...

Reference Number: EMA/203429/2017

Micro Therapeutic Research Article-31 referral - EMA recommends suspension of medicines due to unreliable studies from Micro Therapeutic Research Labs

AdoptedReference Number: EMA/188204/2017

European Commission final decision

Micro Therapeutic Research Article-31 referral - CHMP assessment report

Reference Number: EMA/420215/2017

Micro Therapeutic Research Article-31 referral - Annex II

Micro Therapeutic Research 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.