Mumbai: After ordering a crackdown on loosely controlled drug trials using human subjects in India following a Mint story, the Indian drug regulator is planning a major overhaul in the country’s drug adverse reaction monitoring system.
The Central Drugs Standard Control Organisation is now planning to appoint a team of about 100 clinical pharmacologists across the country, on a contract basis, to collect adverse drug reaction reports and patient complaints from hospitals, clinics and practising clinicians.
“We are not taking any chances now, because the domestic pharma market is growing and a host of new drugs are being launched by domestic as well as foreign companies,” M. Venkateswarlu, India’s drug controller general, told Mint. “Though the new drugs are approved after verifying the clinical trial data, this will not be enough to establish the absolute safety of a drug as these are conducted in limited number of volunteers or patients, which are only indicative. So a regular post-marketing study will only provide the actual response (effects and side effects) of the drug as it has been practically used in a wider patient pool.”
The drug review system, known as pharmacovigilance in industry terms, typically works through collecting adverse reaction reports and analyzing them in the context of safety, efficacy and dosage compliance. It is now being proposed as a regular procedure to keep a close watch on all approved drugs in the post-marketing phase.
Though it is the responsibility of drug manufacturers to do these studies on newly marketed drugs and submit the data to the regulator, the system has been a failure in India as most companies flout the law.
As a result, the country had hardly any drug recalls, even though several drugs marketed here are alleged to have a doubtful safety profile. The system could also be an early-warning system unlike recent cases, including recall controversies over GlaxoSmithKline Plc.’s Avandia diabetes drug and the voluntary recall of cardiac stents by Johnson & Johnson, where Indian authorities are still seeking information from their Western counterparts and the multinational drug companies.
Under the existing Indian drug laws, which fall under the Drugs and Cosmetics Act, every drug maker is bound to conduct post-marketing surveillance (Phase 4 study) of drugs to find any kind of adverse reaction in patients, and submit the real data to the regulator. That study is mandatory as it will generate drug safety data in diverse patients from across the country and the regulator can recall the drug at any point if it finds that the risk associated with the drug is more than the claimed benefit.
Admitted Venkateswarlu, who is on a six-month tenure extension: “Also, since the manufacturers often fail to update the regulator on the feedback that they receive from the doctors and patients, it is always difficult for us to review the safety of the approved drugs on an ongoing basis.”
Venkateswarlu also said that the review of the diabetes drug rosiglitazone (the drug marketed by Glaxo India as Vindia in India) is one of the pharmacovigilance studies being undertaken by an independent team. Rosiglitazone is also marketed here by at least seven local drug makers under different brand names.
The US Food and Drug Administration (FDA), which comes out with regular drug alerts for the information of health care professionals as well as patients, has a very effective feedback registering system within the department along with a very strong pharmacovigilance cell.
“Though US FDA frequently publishes drug reviews and follow-up actions (recalls or restricted-use notifications) on its website, such moves are still unheard of in India,” says C.J. Shishoo, trustee, Consumer Education and Research Centre, an Ahmedabad-based consumer action group.
According to Dr Shishoo, at least half a dozen drugs with dubious safety profiles are still being marketed in India as there were no adverse reports available with the regulator. Rofecoxib, the internationally recalled anti-arthritis drug sold by Merck & Co. as Vioxx, Ceoxx and Ceeoxx; cisapride, one of the most prescribed heartburn drugs sold under the trade names Prepulsid (Janssen-Ortho) and Propulsid (in the US) and discovered by Janssen Pharmaceuticals in 1980; and the popular anti-cold drug phenylproponalamine are some of the controversial molecules still available in the domestic market.
According to a senior official from the central drug regulatory department who does not want to be identified, “Currently our mechanism is grossly inadequate to tackle the issues related to pharmacovigilance as there are no public interaction systems wherein the doctors or patients can (share) their experiences with drugs that they use (with) the regulator directly. Since the department is also facing severe people crunch, it is not able to dedicate special cells or people with the task of collecting patient responses.
“Hence, whenever there is a recall of a drug abroad, we do not have any relevant data to take follow-up actions. This makes the department always dependent on the drug alerts of US FDA or European regulators to initiate an action here.”
Separately, as first reported by Mint on 20 August, the drug controller is also reviewing the licences of another 282 drug combinations, marketed by almost all local drug makers by hundreds of brands each, approved by various state drug controllers, as they were not tested for safety standards.