New Delhi: An audit by India’s drugs quality regulator has found a clinical trial sponsored by Wyeth Pharmaceutical Ltd and monitored by GVK Biosciences Pvt Ltd has violated protocol, standard operating procedure and good clinical practices norms mandatory in the country.

The office of the drugs controller general of India, or DCGI, issued warning letters on Tuesday asking for explanations, based on the audit findings.

Answerable: The headquarters of Wyeth in Madison, New Jersey. Mike Derer / AP

The report was recently submitted to drugs controller general Surinder Singh. Details of the report were shared with Mint.

Mint had first reported on 15 November that DCGI suspended the clinical trial after the death of an infant, who should not have been included in the trial at all as per the so-called exclusion criteria of the protocol.

Good clinical practices, or GCP, are international quality standards provided by the International Conference on Harmonisation, which governments can incorporate into their domestic regulations for clinical trials on human subjects. GCP are mandatory in India.

“Our investigation has revealed that there have been violations of the protocol, the SOP (standard operating procedure) and GCP," said a senior official at the DCGI’s office. “We conducted random checks at St John’s Hospital of the trial." He said that medical files, meant to record subjects’ medical condition and body temperature during their visits for monitoring by the trial investigator, were incomplete. Besides, test drug accountability forms, mandated in the SOP to record each dose administered to the subject, were not filled in, he added.

Moreover, the first step of any clinical trial is to obtain a written consent form, a practice that was not followed. “The written consent was being taken after the clinical investigator conducted a medical examination," said the official, who didn’t want to be named because he isn’t authorised to speak to the media.

Wyeth confirmed having received a communication from the DCGI regarding its phase 3 clinical trial for its advanced vaccine.

“We are confident that all of the topics raised will be adequately addressed to resolve this situation," said Durga Gadgil, director, clinical research and development, Wyeth. “We look forward to providing the DCGI’s office with the information necessary to complete this review and allow for the restart of this study."

“With reference to the Wyeth pneumococcal vaccine trial, GVK Bio has followed all necessary protocols and practices and there has been no violation on our part," GVK Biosciences said in an emailed response, adding that it would be responding to the DCGI’s letter within the stipulated time. Pneumococcal bacteria mainly causes pneumonia and meningitis, besides other diseases.

Calls made to a member of St John’s Hospital’s ethical committee weren’t answered.

An expert said the responsibility for the alleged violations ultimately lies on the study’s sponsor Wyeth.

“There are grave irregularities in the manner in which this trial has been conducted by Wyeth, GVK Bio and St John’s Hospital," said Chandra M. Gulati, one of India’s top experts in drug regulations, and editor of Monthly Index of Medical Specialities.

“First, they violated protocol, which they are duty bound to follow. Second, they did not follow SOP, which makes us wonder if regular examinations on the subjects were conducted at all. We already know that the exclusion criterion was not followed. And the fact that consent form was not signed before the child was even touched is a...violation of ...child rights as well," he said.

This is the first time such an incident has been recorded in India. The clinical trial began in 2007 and was being conducted on 350 children in the country. Some 250 had already been tested before the trials were suspended.