Pharma companies are risking the wrath of India's drugs regulator by ignoring a demand for clinical trials of combination drugs.
Earlier this year, India's Central Drugs Standard Control Organisation (CDSCO) banned 344 fixed-dose combination (FDC) drug products, saying they were unapproved and in some cases included medicines that are "banned, restricted, or never approved internationally owing to adverse effects."
The products in question are drug formulations containing two or more active drugs--combined in a fixed ratio of doses--that are usually available only in a single dosage form. They are generally considered useful for minimizing pill burden and reducing treatment costs.
According to the Indian government, a "very large number" of drugmakers sidestepped central review of FDC medicines and instead submitted them to state licensing authorities. Once approved, the drugs were then rolled out nationwide.
The Drugs Controller General of India (DCGI)--Dr. G.N. Singh--has issued a terse notice to state authorities and industry associations, revealing that so far "hardly any" companies have submitted phase IV (post-marketing) trial protocols for FDCs, as requested by the government back in 2013.
The failure to do so "has been viewed very seriously by this Directorate," the notice continues. The DCGI re-iterates the request to submit trial protocols without indicating what further regulatory action may be taken.
There are also reports that the CDSCO is gearing up to extend its ban. An article in Pharmabiz suggests the agency will soon ban several additional FDCs approved by state licensing authorities.
The decision to ban the FDCs was greeted with consternation by pharma companies, including Sanofi ($SNY), whose diabetes combination Amaryl MP drug--which contains metformin and glimepiride--was caught up in the cull. The French drugmaker is among a number of companies that have opted to challenge the decision in the courts.
Last month, a paper published in The Lancet concluded that the government's action was "necessary to safeguard public health." One in 5 of the banned FDCs were antibiotics and could contribute to antibiotic resistance, the journal said.
In 2015, the same journal also took issue with what it described the "proliferation of irrational metformin FDCs in India," pointing out that metformin combinations are not recommended by international or national treatment guidelines for the management of type 2 diabetes.