The inspection “has raised serious concerns regarding the GCP compliance of the conduct of the clinical part of bioequivalence trials at GVK Bio, Hyderabad, India in the period July 2008 – 2014,” according to the ANSM letter.
As part of the concerns, all MAHs (marketing authorization holders) and applicants must provide information on whether the clinical part of a pivotal bioequivalence study in any of their dossiers was conducted at the CRO GVK Bio Hyderabad, India in the defined period. But ANSM notes that the enquiry is only for the clinical facility at GVK’s Hyderabad headquarters “and it does not concern the bioanalytical facility at the same site.”
ANSM also requested that GVK’s response should cover clinical activities conducted in Hyderabad, India from July 2008 onwards till the present. The company was also asked to provide information on the importance of the bioequivalence studies for dossiers submitted to national competent authorities, and on “the potential impact on the evidence of bioequivalence mitigated by other information in the dossier.”
GVK spokeswoman Dorothy Paul told us that the May inspection covered nine studies conducted at the Hyderabad facility that had "check-out ECGs [electrocardiograms]." Clinogent, which is the new name of GVK's clinical research business development unit, "is closely working with the authorities to resolve the queries to their satisfaction."
"No decision on either rejection or approval is made yet," Paul added.
The letter comes about five years since GVK was cited for two deaths in its clinical trials, according to a study in the Indian Journal of Medical Ethics.
The first case pertains to the death of an infant while being part of a trial on a pneumonia vaccine developed by Wyeth Pharmaceuticals, at St John’s Hospital in Bangalore.
The DCGI (Drug Controller General of India) eventually cancelled the trial after media reports were published. GVK, however, maintained that the infant died of an underlying condition, a serious congenital heart disease, and was not even administered the new vaccine as the child was part of the control group.
The second case pertained to the death of a young adult in a Hyderabad-based facility after being subject to a bioequivalence study of the cardiac drug Felodipine.
“Here again GVK has denied any lapse on its part and claimed that the death occurred over a week after the drug was administered, by which time the drug would have been ‘washed out’ of the body,” according to the Journal. “What is particularly curious about this case is GVK’s additional claim that the subject was a part of many other studies. The company claimed that the subject “has been participating in similar bioequivalence studies in various CROs.’… This raises the suspicion that the deceased was a ‘professional’ subject of studies and trials and was recruited after being provided monetary incentives. Not only would such a practice be unethical, it would also be dangerous given the cocktail of different drugs to which such a participant would be subjected [sic] GVK.”