India''s Drug Act makes it possible for FDCs (fixed dose combinations) to evade CDSCO (Central Drugs Standard Control Organisation) approval and is in urgent need of an overhaul.
India’s Drug Act has aided proliferation of harmful combination drugs, many of it available on retail shelves, without any clinical trials and with little medical rationale, a study has found.
This has helped harmful fixed dose combinations of metformin, used for managing diabetes, to evade approval as well as price controls, reputed medical journal Lancet has said.
The findings, shared exclusively with TOI, show that there is hardly any evidence to support its use and suggest that the regulator should withdraw all licences until the manufacturers provide scientific rationale for their safety.
"India’s Drug Act makes it possible for FDCs (fixed dose combinations) to evade CDSCO (Central Drugs Standard Control Organisation) approval and is in urgent need of an overhaul," Lancet says in its analysis.
Though metformin fixed dose combinations are not recommended by international or national treatment guidelines for diabetes control, over 500 marketed brands are available in the country. Some of the top-selling metformin combination medicines include Amaryl MP, Gemer P1, Glimy M, Glyciphage PG1 and Pioglar GF.
Globally, there is little use of metformin combinations, Lancet says.
"Many such dubious drug combinations should be banned, and taken off the market. Strict criteria and testing should be applied to screen any new FDC (fixed dose combination), and also background and past performance of manufacturing company should be strictly monitored," says DrAnoopMisra, chairman of Fortis CDOC (hospital for diabetes and allied specialities).
"This short and elegant analysis highlights what primarily plagues Indian pharma sector, possibility of many substandard FDCs of frontline diabetes drugs being available in market," he adds.
Although 41 metformin FDCs have been approved for diabetes in India, the rationale (for their approval) is not clear as the drug regulator does not publish grounds for new drug approvals, while the country’s clinical trials registry, which has been mandatory only since 2009, has no data of these trials conducted in India. Sales volumes of metformin FDCs outstrip metformin (single drug) formulations by a factor of three to one, and account for 56% of all oral diabetic drug sales, while disturbingly, only one of these is marketed outside India.
"Our research shows that the short-duration trials sponsored by multinational companies failed to consider the balance of any possible advantage of FDCs over potential disadvantages, and did not provide robust evidence of the efficacy and safety of these combinations. Furthermore, when these trials were scrutinized against WHO guidelines for approval of FDCs, none met the recommended criteria for efficacy and safety. We concluded that CDSCO must make public the evidence it used when granting approval of metformin FDCs and the basis for efficacy and safety," Lancet says.
Earlier, an expert committee chaired by Ranjit Roy Chaudhury stated that about 85,000 drug formulations available here should not be marketed at all since the scientific basis for their approval is in need of urgent review. A parliamentary report found that new drug approvals were being granted without the necessary clinical trials.
Of particular concern were approvals for oral fixed dose combinations.
FDCs-which are a peculiar feature of the Indian pharmaceutical landscape, with an estimated 5,000 available here-have faced flak over the years, with the drug regulator directing states to stop giving licences and ban some of them.
However, this action is yet to be taken and many harmful ones are still available on retail shelves.