Credit: Steven Harbour
The European Medicines Agency (EMA) has recommended suspending a number of drugs that were approved in the European Union (EU) based on clinical studies conducted at GVK Biosciences in Hyderabad, India.
An inspection of the site suggested GVK Bio employees may have manipulated data from trials that took place there.
So the EMA compiled a list of drugs—which includes clopidogrel, dexamethasone, and tacrolimus, among others—that should be suspended.
However, the EMA said there is no evidence of harm or lack of effectiveness linked to the conduct of studies by GVK Bio, and patients should continue taking their medicines as prescribed.
The EMA’s opinion has been forwarded to the European Commission (EC), which will adopt a legally binding decision.
It was at the request of the EC that the EMA’s Committee for Medicinal Products for Human Use (CHMP) reviewed the drugs set to be suspended.
An inspection by the French medicines agency, Agence nationale de sécurité du médicament et des produits de santé (ANSM), in May 2014 uncovered “non-compliance with good clinical practice” at the GVK Bio site in Hyderabad.
The ANSM inspector analyzed 9 studies conducted there from 2008 to 2013 and found evidence suggesting that data from electrocardiograms (ECGs) had been manipulated. It appeared that GVK Bio employees were taking multiple ECGs of one volunteer and presenting them as ECGs of other volunteers.
The EMA said the systematic nature of these data manipulations, the extended period of time during which they took place, and the number of staff members involved casts doubt on the integrity of the way trials were performed at the Hyderabad facility and on the reliability of data generated there.
With this in mind, the CHMP looked at more than 1000 pharmaceutical forms and strengths of medicines studied at the site. For more than 300 of the medications, there was sufficient data from other sources to support the drugs’ authorization, so these will remain on the market in the EU.
For drugs that lack data from other studies, the CHMP recommended suspension unless they are of critical importance for patients because alternatives will not be able to meet patients’ needs.
Whether a medicine is critical for patients will be determined by the national authorities of EU member states, depending on the situation in their country. For drugs that are considered critical, companies developing those drugs will be given 12 months to submit additional data.
The CHMP’s recommendation will be sent to the EC for a legally binding decision that will apply to all EU member states whether or not they have taken interim measures to suspend medicines.
GVK Bio responds
GVK Bio said an internal audit conducted following the ANSM inspection suggested that standard operating procedures were followed for the 9 trials analyzed. The organization also sought the opinion of 4 independent cardiologists, who said it was difficult to determine if the ECGs belong to the same volunteer or more than one person.
GVK Bio presented this information to the ANSM, but the agency concluded that the studies did not meet good clinical practice guidelines and should be rejected.
Following subsequent meetings and analyses, the EMA came to a similar conclusion—that the overall findings cast doubt on the results of trials conducted at the Hyderabad facility from 2008 to 2014.
GVK Bio said it respects the EMA’s decision, but their recommended suspension of drugs is “unprecedented and highly disproportional” for a few reasons.
First, the ANSM said the ECGs in question were not essential to demonstrate the bioequivalence of the drugs tested, and the agency’s recommendation to reject the 9 studies was a “precautionary” measure.
The ANSM also said the observations made during the inspection should not be extrapolated to other trial-related activities at the Hyderabad site or GVK Bio’s other site in Ahmedabad.
And finally, the EMA itself said there is no evidence proving that the drugs in question are ineffective or pose a risk to human health.
