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Global AMR Threat: Centrally Approved & Unapproved Antibiotic Formulations Sold In India

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  • Global AMR Threat: Centrally Approved & Unapproved Antibiotic Formulations Sold In India

    Global AMR Threat: Centrally Approved & Unapproved Antibiotic Formulations Sold In India


    The global spread antimicrobial resistance (AMR) has been of great concern for years, but gained new prominence just over 7 years ago when The Lancet published a study (see NDM-1: A New Acronym To Memorize) by Walsh, Toleman, Livermore, et al. that awakened the world to the emergence and growing prevalence of the NDM-1 (New Delhi metallo-β-lactamase) enzyme.
    Widely found on the Indian sub-continent, but increasingly found around the globe, this enzyme can make many types of bacteria resistant to a wide spectrum of antibiotics.
    Of particular concern, this enzyme (and others like it) can be carried by a plasmid – a snippet of portable DNA - that can be horizontally transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species), conveying resistance to them as well.

    Six months after the first Lancet article - in April, 2011 - the same researchers published another study that found the NDM-1 enzyme in 4% of New Delhi’s sampled drinking water sources, and 30 per cent of the sewage tested. Most alarmingly, the researchers also identified 11 new species of bacteria carrying the NDM-1 gene, including strains which cause cholera and dysentery.

    Since then, we've seen scattered variants of NDM-1 emerge around the globe, including NDM-2, NDM-4, NDM-5, NDM-7 and NDM-9 along side a growing list of other resistant pathogens including CRE (Carbapenem-resistant Enterobacteriaceae) and mcr-1 (see MCR-1: The Return Of The Plasmids).
    The rise of antibiotic resistance - including these emerging NDM enzymes - has long been linked to the overuse and misuse of antibiotics. A practice that is still widespread in many parts of the world, but has been particularly rampant on the Indian sub-continent.
    In 2014, in EID Journal: Acquisition of Drug Resistant Genes Through International Travel, we looked at a study from the Netherlands tested that 122 healthy travelers both before and after making an international trip for evidence that they carried one of (several) antimicrobial resistance-inducing genes.
    They found a high rate of resistance genes in the commensalgut bacteria of returning travelers – particularly those visiting Southeast Asia and the Indian subcontinent .
    After years of denials, delays, and debate, in 2014 India finally placed restrictions on the sale of antibiotics without a prescription (see Times of India report 46 drugs under strict prescription norm) although reports since then have left serious doubts as to how well these regulations were being enforced.
    Today we've a new study, published in the British Journal of Clinical Pharmacology, that finds despite new regulations, the levels of illicit and unapproved antibiotic formulations manufactured and sold in India continues to climb.
    A link to and some excerpts from the study, followed by a link to a press release from Queen Mary University of London. You'll want to read both in their entirety, after which I'll post some additional links at the end.
    Threats to global antimicrobial resistance control Centrally approved and unapproved antibiotic formulations sold in India

    Accepted manuscript online: 4 February 2018Full publication history
    DOI: 10.1111/bcp.13503 View/save citation
    Cited by (CrossRef): 0 articles Last updated 05 February 2018


    Rising antimicrobial resistance (AMR) is a global health crisis. India has among the highest resistance rates and antibiotic consumption internationally. Extensive use of fixed dose combination (FDC) antibiotics and of unapproved formulations are claimed contributory factors but there has been no systematic examination of formulations or volumes sold.

    To investigate the regulatory approval status and sales volumes of systemic antibiotics marketed in India.


    This was an ecological study using regulatory records in India, the UK and US to determine the approval status in each country of systemic antibiotic FDC and single drug formulations (SDFs) marketed in India. Pharmatrac? sales data were used to determine the formulations and volumes sold in India (2007-2012), branded-product numbers, and manufacturers.

    Of 118 systemic antibiotic FDC formulations marketed in India, 43(36%) were approved but 75 (64%) had no record of regulatory approval; 5(4%) formulations were approved in the UK and/or US. Almost half of formulations (58/118,49%) comprised dual antimicrobials, most unapproved in India (43/58,74%), and many pharmacologically problematic. In contrast, 80/86(93%) SDFs were approved in India and over two-thirds in the UK and/or US.

    Total antibiotic sales increased by 26% from 2056 Million-Units (2007-08) to 2583 Million-Units (2011-12). FDC sales rose by 38% versus 20% for SDFs. By 2011-12, FDCs comprised one-third of sales (872 Million-Units). Over one-third of FDCs sold (300.26 Million-Units, 34.5%) were of unapproved formulations. Multi-National Companies manufactured unapproved formulations and accounted for 19% of FDC and of SDF sales annually.


    Sales in India of antibiotic FDCs, including unapproved formulations, are rising. In the context of increasing AMR rates nationally and globally, unapproved antibiotic FDCs undermine India's national AMR strategy and should be banned from sale.
    (Continue . . . )
    Millions of unapproved antibiotics are being sold in India, according to a new study by researchers at Queen Mary University of London and Newcastle University.
    5 February 2018
    The research, 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.
    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.
    Exacerbating antimicrobial resistance

    Of 118 different formulations of FDCs being sold in India between 2007 and 2012, the team found that 64 per cent (75) 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.
    Lead author Dr Patricia McGettigan from Queen Mary's William Harvey Research Institute said: “Selling unapproved, unscrutinised 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.”
    (Continue . . . .)

    Other recent blogs on this growing global threat include:
    All medical discussions are for educational purposes. I am not a doctor, just a retired paramedic. Nothing I post should be construed as specific medical advice. If you have a medical problem, see your physician.