The investigation follows an inspection by the French regulator ANSM at the Indian CRO (contract research organization), which raised concerns about study data dating back to July 2008 used to support the marketing authorisation applications of generic medicines.
ANSM sent a letter to marketing authorization holders with regard to the use of GVK BIO’s clinical facility in Hyderabad, India. A GVK spokeswoman previously told us that the ANSM inspection involved the use of ECGs.
But Sabine Jülicher, Head of Unit, Medicinal products – authorisations at the EMA, cited a number of ANSM’s findings in a letter to CHMP, including: “falsifications of electrocardiograms were detected in each and every one of the 9 trials inspected by the ANSM.”
“The falsification of these ECGs was performed by at least 10 different individuals. The falsifications took place between at least July 2008 and 2013…the systematic nature of the falsifications of electrocardiograms, the extended period of time during which they took place and the number of members of staff involved highlight critical deficiencies in the quality system in place at GVK Bio's clinic in Hyderabad,” Jülicher writes.
“They also show a lack of GCP training, awareness and understanding of members of GVK Bio staff, a lack of understanding by them of the importance of data integrity and of the possible consequences of their acts, as well as a lack of overview of clinical trial activities by the investigators,” she says. “The seriousness of the deficiencies identified and the lack of GCP compliance at GVK Bio's clinic in Hyderabad raise questions as to the acceptability of the clinical part of all other bioequivalence trials performed at that site in support of marketing authorisations applications.”
The EMA’s Committee for Medicinal Products for Human Use (CHMP) will now review available data to determine which medicines are affected by the inspection findings and issue a recommendation on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the EU.
GVK spokeswoman Dorothy Paul told us: "This is a natural next step as per referral procedure initiated by EMA as a follow up of ANSM inspection."
EMA requests that GVK respond in writing several questions, including: “Discuss the root cause of this issue affecting the GVK Biosciences-Hyderabad site and provide assurance that these issues” are confined to the Hyderabad site from July 2008 to present.
In addition, the European regulator calls on GVK to “indicate which measures have been undertaken to investigate if this is a corporate issue.”
As far as a timeline, GVK has until Oct. 3 to respond. Between Oct. 13-23, the EMA rapporteur and co-rapporteurs’ assessment reports will be circulated to CHMP, which will offer comments and then update the reports. A list of outstanding issues and CHMP discussion will begin on Oct. 23.