An infant in Bangalore, who had a pre-existing cardiac disorder, died during a clinical trial for an advanced pneumonia vaccine. And India's rules prohibit testing on human subjects with such conditions without prior approval of the Drugs Controller General of India,LiveMint reports.
Wyeth had been permitted to conduct tests only on healthy babies, according to the regulator, LiveMint continues, adding that the trial began last year was being conducted on 350 healthy babies who were between 42 and 72 days old. Some 250 have already been tested and Wyeth is still allowed to collect the data.
"The baby was suffering from a cardiac abnormality and should not have been included in the trial at all. It seems that the ‘inclusion-exclusion’ criteria protocol has not been adhered to by the investigator,” Surinder Singh, drugs controller general, tells LiveMint. “We have suspended all further trials across the country.”
The incident brings to the fore an ongoing debate over allowing foreign drugmakers to conduct what are called phase III trials here for a drug that is not marketed anywhere else in the world. Until January 2005, human trials for a molecule developed outside India were allowed only under if the drug was already approved for use abroad and was sold in the market.
Though the Indian regulator has suspended several drug trials in the past, all of them have been over adverse reactions or efficacy issues, and not for violation of the rules themselves, according to drug regulation experts.
“This is the first reported instance I can recall,” Chandra Gulati, one of India’s top experts in drug regulations, and editor of Monthly Index of Medical Specialities, tells LiveMint.
Under the inclusion-exclusion protocol, if the investigator or drugmaker decides to include or exclude a subject from its trial for not fitting into approved criteria such as age, weight and health conditions, prior permission must be sought from the licensing authority, in this case, DCGI.
It was not immediately clear at which link in the testing chain the mistake occurred. Wyeth Ltd, the Indian unit, said the tests were conducted by GVK Biosciences, contracted for the trials, LiveMint writes, although Singh says Wyeth had conducted the trials on its own.
A GVK Biosciences spokeswoman tells LiveMint it couldn’t comment because of “client confidentiality”. The tests were done at Bangalore’s St John’s Hospital’s National Academy of Health Sciences.
The Wyeth phase III trial was part of global clinical trials to assess the safety, tolerability and immunogenicity of a pneumococcal conjugate vaccine that fights 13 strains of bacteria compared with seven strains in the company’s current vaccine, Prevnar.
Singh says he would be sending his drug inspectors to investigate the death of the baby, next week. “Further action will be taken based upon the outcome of our investigation,” he tells LiveMint. “We want to take very stern action. You (the company) should select the right type of child and subject. When the child has died, you are telling us that the child had a cardiac abnormality. We will not allow companies to fiddle with the safety system set out for clinical trials in India.”
Wyeth says the child who died had been administered Prevnar and not the new 13-strain variant. “The event occurred in the control group, which used the current worldwide standard vaccine for prevention of pneumococcal disease and which has been administered safely more than 200 million times worldwide during the past seven years,” a Wyeth spokesperson wrote LiveMint in an email. The test was comparing efficacy of Prevnar and the new variant.
Gulati predicted Wyeth would be eventually held responsible even if it contracted a testing firm for the trials: “Ultimately, the sponsor is legally responsible though if there is any injury, then in a court case summons will also be issued to the investigator (for negligence), hospital (for not monitoring the trial properly) and DCGI (for not conducting inspection of the trial).”