A study by Newcastle University and Queen Mary University of London, published today in the British Journal of Clinical Pharmacology, found that multinational companies continued to manufacture many unapproved formulations, despite pledging to tackle rising antimicrobial resistance.

These findings highlight serious hurdles for controlling antimicrobial resistance in India, which has among the highest antibiotic consumption rates and sales in the world, and has had parliamentary investigations into failures of the country’s drug regulatory system.

Indian market

The researchers examined figures for fixed-dose combination (FDC) antibiotics (formulations composed of two or more drugs in a single pill) and single-drug formulation (SDF) antibiotics (composed of a single drug) on the market in India.

Of 118 different formulations of FDCs being sold in India between 2007 and 2012, the team found that 64% were not approved by the national drugs regulator, the Central Drugs Standard Control Organisation (CDSCO), even though the sale of unapproved new medicines is illegal in India. Only five of the formulations were approved in the UK or US.

The 118 FDC formulations gave rise to more than 3,300 brand-named products made by almost 500 pharmaceutical manufacturers, including multinational companies.

By 2011-2012, FDCs made up a third of total antibiotic sales in India, yet 34.5% of these sales (comprising 300 million units) were unapproved formulations. Many of the FDCs combined two antimicrobials, often poorly chosen and likely to exacerbate resistance problems.

The study also found that multinational companies manufactured nearly 20% of the FDCs and SDFs sold. As many as 20 FDC formulations manufactured by multinational companies had no record of CDSCO approval, and only four of the 53 FDC formulations made in India by multinational companies had UK or US regulatory approval.

In contrast, 94% of multinational companies’ SDFs were CDSCO-approved, and more than 70% had UK or US regulatory approval.

Change needed

Professor Allyson Pollock, director of the Institute of Health and Society at Newcastle University, co-author of the research, said: “Limiting antimicrobial resistance is a strategic goal of the WHO and countries worldwide—governments and regulators must take all necessary steps to prevent the production and sale of illegal and unapproved medicines and scrutinize the actions of multinational companies.”

The researchers argue that changes needed to achieve the WHO's vision of good use of antibiotics include banning the sale of unapproved FDC antibiotics and enforcing existing regulations to prevent unapproved and illegal drugs reaching the market.

Improved access to health care to reduce non-prescription sales is also needed, alongside research to understand why doctors complicate problems by prescribing unapproved antibiotics.

Lead author Dr. Patricia McGettigan, from Queen Mary University of London, said: “Selling unapproved, unscrutinized antibiotics undermines measures in India to control antimicrobial resistance. Multinational companies should explain the sale of products in India that did not have the approval of their own national regulators and, in many cases, did not even have the approval of the Indian regulator.”