Unapproved Drug Combinations Complicate AMR Battle in India

Patricia McGettigan, MD

A new study has found that the sale of unapproved formulations of antibiotics is continuing to rise in India, despite growing fears about global antimicrobial resistance (AMR) rates, and industry pledges to combat the problem.

British and Indian researchers found that of the 118 systemic antibiotic fixed-dose combinations (FDCs) on the market in India, nearly two-thirds (64%) hadn’t been approved by the country’s pharmaceutical regulator, the Central Drugs Standard Control Organization (CDSCO). Of the 118 FDCs studied, only 5 had been approved in either the United States or the United Kingdom. Those 118 FDCs were sold under 3300 brand names and manufactured by more than 500 companies, both domestic firms and multinational corporations. The data cover sales between 2007 and 2012.

Lead author, Patricia McGettigan, MD, of the William Harvey Research Institute at Queen Mary University of London, said these unapproved medications get to consumers in multiple ways, both with a prescription and without, even though the latter is illegal. She told Contagion^® that both physicians and pharmacies have a role to play in helping combat AMR by curbing rampant antibiotic sales.

“Pharmacies could enforce the requirement to have a prescription before antibiotics are dispensed,” said Dr. McGettigan. “Doctors could make sure to issue prescriptions where they are reasonably certain that the patient's illness is due to bacterial infection that is likely to be responsive to antibiotic treatment.”

However, Dr. McGettigan said there are a number of complicating factors. For one, many Indians pay for health care out-of-pocket, and thus seeing a doctor to get a prescription isn’t financially feasible for many patients.

In a letter published this month in The Lancet, Johns Hopkins University’s Sachin R. Atre, PhD, said part of the problem is a lack of scientific regulatory manpower to cohesively tackle the problem.

“When I asked pharmacists in rural India about visits by drug inspectors, the frequent answer was ‘once in a year or 2,’ which might explain the grim regulatory control situation there,” Dr. Atre wrote.

The FDC landscape is starkly different from the landscape for sales of single-drug formulations (SDFs), the latter of which make up two-thirds of total antibiotic sales in India. In the case of SDFs, 93% of the drugs on the market were approved for sale in India, and more than 70% had been approved in the United States or the United Kingdom.

Altogether, antibiotic sales in India jumped by 26% over the course of the study, from 2007 to 2012. Sales of SDFs rose by 20%, but sales of FDCs soared by nearly double that rate, 38%. Those increases come against a backdrop of growing concern about AMR, something the World Health Organization has been working to combat. Banning the sale of unapproved FDCs is seen as an important key to solving that problem. Data of drug sales from 71 countries between 2000 and 2010 showed India had the highest per-capita consumption of antibiotics.

The problem is not unknown to regulators and government officials in India, but Dr. McGettigan said the country’s approach to fixing the problem has been “rather odd.”

For instance, instead of simply banning the sale of the unapproved drugs, the CDSCO asked states to order drug companies to file show cause notices, in which the drug companies were asked to defend the drugs’ sales and submit applications to have the drugs approved. Some 6000 applications were received. That’s a big number, but Dr. McGettigan said it’s unclear what it actually represents.

“Who knows how many unapproved drugs were on the market for which no application was submitted and there is no record of whether all companies making/selling centrally unapproved drugs chose to respond to the letters from the state authorities,” she stated. Moreover, efforts to ban specific FDCs have been met by legal challenges.

Dr. McGettigan also noted that the pharmaceutical industry is powerful in India, and not keen to submit to regulation. She pointed to a 2014 letter from the Indian Drug Manufacturers’ Association written to India’s Ministry of Health and Family Welfare. In the letter, the trade group contends that CDSCO approval isn’t necessary for FDCs already in use, “since the acceptance by the medical profession serves as a pointer to their efficacy and safety.”

The association went on to say that if there were safety concerns, sales would dwindle, and the drugs would disappear from the market.