Serial testers and cursory checks: India’s flawed generic drug trials business
Over the past two years, international regulators have suspended or banned medicines tested by four major Indian CROs after finding manipulation of clinical trial data and other violations.
Issues found at Indian CROs are “a big problem that is gaining more and more attention from all sorts of agencies,” said Anders Fuglsang, a consultant and former regulator long involved in audits and inspections of CROs around the world on behalf of international regulatory agencies and companies.
Last year, the European Union banned about 700 medicines that had been approved based on clinical trial data provided by GVK Biosciences, then India’s largest CRO. European regulators said they found GVK had manipulated data concerning the heart readings of patients taking part in the study. GVK denied any violation, but several large drugmakers that had won drug approvals based on GVK’s data were asked to re-apply for approval with fresh evidence.
Such re-testing is a headache for drugmakers, as it is expensive, and delays lead to a loss in sales, said Nilesh Gupta, managing director of India’s Lupin Ltd, which was one of the companies to be affected by a U.S. ban on trials by Semler earlier this year.
GVK, part of the Indian conglomerate GVK Group, has since limited its business interests in the generic drugs testing business, said Shankar Chelluri, a spokesman for the company. Overall, sentiment toward the generic drug trials business is weak, Chelluri said.
Another CRO, Quest Life Sciences, was found last year to have manipulated clinical data on certain trials, according to inspection reports from the WHO and the UK’s medicines authority. The Spanish and German regulators had also found problems with Quest’s trials, and the WHO said it found Quest had falsified data on drugs including the antibiotic doxycycline hyclate and HIV/AIDS drugs lamivudine, zidovudine and nevirapine.
Quest managing director T.S. Jaishankar said his CRO, which has conducted dozens of generic drug trials for companies including India’s top drugmaker Sun Pharmaceutical Industries, has since invested heavily in improving its systems and been cleared by all international regulators. In a response to Reuters, a spokeswoman for the European Medicines Agency said they were “closely monitoring” the involvement of Quest in the drug approval applications they receive.
India, like other countries, has ethics committees – groups of independent experts – meant to approve the design and conduct of clinical trials. Their stamp of approval is required by foreign regulators considering allowing a generic drug to be sold. However, these committees depend on the CROs for reimbursement in exchange for reviewing trials. Three members of different committees Reuters spoke to said national guidelines did not clearly define their roles and responsibilities.
In the wake of trial data manipulation scandals at CROs in the past three years, many large drugmakers including Swiss firm Novartis, have been shifting more critical trials back to the United States and Europe, according to consultants and industry executives.
Novartis is also ramping up its own checks of Indian CROs, said Bodo Lutz, a data integrity officer at the Swiss firm. Speaking on the sidelines of a conference in Hyderabad in July, he said: “We can’t rely on the regulators … we’re increasing our own audits.”
VOLUNTEERING “LIKE AN ADDICTION”
Prakash, the former mechanic, said he was never asked by CROs, and their ‘agents’ who approached him for studies, about whether he had recently taken part in another trial.
“Everybody does it. Once you start getting the money, it’s very hard to quit. It’s like an addiction,” said Prakash.
He said after the first study, he began to regularly receive messages on his phone and Facebook, often from agents working on behalf of CROs, informing him about ongoing clinical trials where volunteers were required. Such messages included three key things: the city where the trial was being conducted, the total pay offered, and the “blood loss”, or the amount of blood the volunteer will need to provide.
Venkatesh, from the southern city of Tirupathi, described traveling from Chennai to Hyderabad and then to Bangalore and Mangaluru for different trials.
“I know of several people who participate in three or four trials in the same month,” said Venkatesh, who stopped volunteering two months ago and has since married. He did not want to be referred to by his full name.
Prakash said he was paid 10,000-30,000 rupees ($147-$441) per trial, depending on the duration and type. He stopped participating after his health began to deteriorate last year at age 25.
He now works at a call center earning 20,000 rupees a month, but, despite knowing the risks, entered two more trials recently to raise cash.
“I needed some money desperately so I did it, but I won’t do it again,” he said.
(Additional reporting by Aditya Kalra in New Delhi; Editing by Martin Howell)