GVK Biosciences - referral

Current status

European Commission final decision

Overview

GVK Biosciences: European Medicines Agency confirms recommendation to suspend medicines over flawed studies

Medicines considered critically important for patients to remain available

On 21 May 2015, the European Medicines Agency (EMA) confirmed its recommendation to suspend a number of medicines for which authorisation in the European Union (EU) was primarily based on clinical studies conducted at GVK Biosciences in Hyderabad, India. This is the outcome of a re-examination requested by marketing authorisation holders for seven of the medicines concerned.

EMA's Committee for Medicinal Products for Human Use (CHMP) had adopted its original recommendation in January 2015 following an inspection of GVK Biosciences' site at Hyderabad by the French medicines agency (ANSM) that raised concerns about how GVK Biosciences conducted studies at the site on behalf of marketing authorisation holders.

The inspection revealed data manipulations of electrocardiograms (ECGs) during the conduct of some studies of generic medicines, which appeared to have taken place over a period of at least five years. Their systematic nature, the extended period of time during which they took place and the number of members of staff involved cast doubt on the integrity of the conduct of trials at the site generally and on the reliability of data generated.

During the re-examination, the CHMP concluded that concerns about reliability of the clinical studies remain and therefore maintained its recommendation of January 2015 to suspend medicines for which no supporting data from other studies were available. This is with the exception of one medicine included in the re-examination for which concerns about studies were addressed. This medicine was removed from the list of medicines recommended for suspension.*

As a result of the CHMP's January 2015 opinion and the re-examination, around 700 pharmaceutical forms and strengths of medicines studied at the Hyderabad site were recommended for suspension. For around 300 other pharmaceutical forms and strengths, sufficient supporting data from other sources had been provided; these medicines will therefore remain on the market in the EU.

The Products for which the marketing authorisations are recommended for suspension by the CHMP on 21 May 2015 is available on the EMA website.

The CHMP noted that there is no evidence of harm or lack of effectiveness linked to the conduct of studies by GVK Biosciences at Hyderabad. Some of these medicines may remain on the market in some countries if they are of critical importance for patients because alternatives cannot meet patients' needs.

The decision on whether a medicine is critical for patients lies with the national authorities of EU Member States. For medicines that are considered critical, companies are given 12 months to submit additional data.

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

The CHMP's recommendation was sent to the European Commission for a legally binding decision. The Commission has issued its decision which applies to all Member States irrespective of whether or not they have taken interim measures to suspend medicines.

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^* Bivolet (nebivolol) 5 mg tablets (marketing authorisation holder: Neo Balkanika EOOD); the product has now been removed from the list of medicines recommended for suspension.

Information to patients and healthcare professionals

A number of medicines are being considered for suspension in EU countries following concerns about how studies had been conducted at GVK Biosciences' site in Hyderabad, India. Patients and healthcare professionals are advised of the following:

• There is no evidence of harm or lack of effectiveness with any of the medicines linked to studies conducted by GVK Biosciences.
• Some medicines considered critical for patients will remain on the market in some countries pending the submission of new data.
• National authorities in the EU will consider how critical individual medicines 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 doctor or pharmacist if they have any questions.

More about the medicines

The review covered nationally authorised medicines whose marketing authorisation applications included clinical data from studies conducted by GVK Biosciences at its Hyderabad site.

More about the procedure

The review was initiated on 25 September 2014 at the request of the European Commission, under Article 31 of Directive 2001/83/EC, in relation to findings by the French medicines agency (ANSM) of non-compliance with Good Clinical Practice (GCP) at the GVK Biosciences' site in Hyderabad, India.

The review was carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which adopted in January 2015 an opinion on the marketing authorisation of these medicines.

Following a request from some marketing authorisation holders, the CHMP re-examined its January 2015 opinion. The CHMP's final opinion was forwarded to the European Commission, which issued a final legally binding decision applicable in all EU Member States on 16/07/2015.

National authorities will decide if some of the medicines recommended for suspension are critical in their countries.

GVK Biosciences Article-31 referral - GVK Biosciences: European Medicines Agency confirms recommendation to suspend medicines over flawed studies

Reference Number: EMA/466132/2015

Key facts

About this medicine

• Approved name:
  GVK Biosciences
• International non-proprietary name (INN) or common name:
  • esomeprazole magnesium
  • candesartan cilexetil
  • nebivolol
  • desloratadine
  • donepezil
  • repaglinide
  • candesartan
  • esomeprazole
  • alendronic acid
  • ropinirole
  • cefpodoxime
  • quetiapine
  • trimetazidine
  • bosentan
  • tramadol
  • paracetamol
  • escitalopram
  • trimetazidine hydrochloride
  • entacapone
  • valsartan
  • hydrochlorothiazide
  • donepezil hydrochloride
  • ropinirole hydrochloride
  • clopidogrel hydrochloride
  • escitalopram oxalate
  • metformin hydrochloride
  • trimetazidine dihydrochloride
  • rizatriptan benzoate
  • metformin
  • fluconazole
  • eletriptan
  • rizatriptan
  • ebastine
  • ibuprofen
  • desmopressin
  • aciclovir
  • levetiracetam
  • irbesartan
  • venlafaxine
  • ciprofloxacin
  • cefpodoxime proxetil
  • tacrolimus
  • fexofenadine hydrochloride
  • phenoxymethylpenicillin
  • amlodipine besilate
  • metoclopramide
  • clopidogrel
  • levodopa
  • carbidopa
  • entacapone
  • atorvastatin
  • telmisartan
  • clindamycin hydrochloride
  • metoclopramide hydrochloride
  • clonazepam
  • clobazam
  • dexamethasone
  • thiamine hydrochloride
  • tramadol hydrochloride
  • pioglitazone
  • dipyridamole
  • fexofenadine
  • amlodipine
  • pantoprazole
  • hydrocortisone

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-31/1408
• 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:
  21/05/2015
• EC decision date:
  16/07/2015

All documents

Procedure started

GVK Biosciences Article-31 referral - CHMP list of questions to all marketing-authorisation holders

Reference Number: EMA/CHMP/658332/2014

GVK Biosciences Article-31 referral - Review started

Reference Number: EMA/580140/2014

GVK Biosciences Article-31 referral - CHMP list of questions

Reference Number: EMA/590962/2014

GVK Biosciences Article-31 referral - Timetable for the procedure

Reference Number: EMA/591005/2014 Rev. 5

GVK Biosciences Article-31 referral - Notification

Opinion provided by Committee for Medicinal Products for human Use

GVK Biosciences Article-31 referral - GVK Biosciences: European Medicines Agency confirms recommendation to suspend medicines over flawed studies

AdoptedReference Number: EMA/324341/2015

GVK Biosciences Article-31 referral - GVK Biosciences: European Medicines Agency recommends suspending medicines over flawed studies

Reference Number: EMA/37763/2015

European Commission final decision

GVK Biosciences Article-31 referral - GVK Biosciences: Final assessment report following the re-examination procedure

AdoptedReference Number: EMA/348074/2015

GVK Biosciences Article-31 referral - Annex II

GVK Biosciences Article-31 referral - Annex III

GVK Biosciences Article-31 referral - Annex I

GVK Biosciences Article-31 referral - GVK Biosciences: European Medicines Agency confirms recommendation to suspend medicines over flawed studies

Reference Number: EMA/466132/2015

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.