On 23 January 2020 the Indian Ministry of Environment, Forest and Climate Change (MoEF&CC) announced stringent standards on concentrations of antibiotics found in the waste discharged by pharmaceutical factories into rivers and the surrounding environment.
By doing so it became the first state regulator anywhere in the world to introduce such standards, meant to reduce chances of creating drug-resistant bacteria. Currently, there are no laws specifically aimed at curtailing antibiotics in wastewater in order to limit antibiotic resistance, even in Europe or the USA.
The proposed Environment (Protection) Amendment Rules, 2019, which sets limits on residues of 121 antibiotics in the treated effluents discharged by drug production units, was open to public comments till March 23 and is expected to be finalized subsequently.
The move has been welcomed by global experts, who have long worried that India’s antibiotic production facilities were dumping large quantities of inadequately treated effluent into the environment, increasing the selective pressure for emergence of resistant bacteria. Professor Joakim Larsson, director of the Centre for Antibiotic Resistance research at the University of Gothenburg, Sweden was quoted by the Bureau of Investigative Journalism as calling the bill “a great leap forward” and critically important, but also warning it could be challenging to enforce.
The huge volumes of antibiotic production and use in the last eight decades have made many pathogenic bacteria resistant to a variety of antibiotics, resulting in common infectious diseases becoming untreatable and increasing costs of treatment.
While for a long time global focus was on the use and misuse of antibiotics in the human and animal health sectors in recent years researchers and public health campaigners have pointed to the role of waste from pharmaceutical production facilities as a significant driver of AMR.
Antibiotics in the environment: from production of active pharmaceutical ingredients in the medicines
A main cause of antibiotics in the environment is the production of the active pharmaceutical ingredient (API), the working element of a medicine, which is often produced in a separate facility.
In 2009, when researchers analyzed water from wells in six villages surrounding Hyderabad’s industrial suburb Pattancheru, the largest medicine production hub in India, all of them were found to be contaminated with drugs. Ciprofloxacin, enoxacin, cetirizine, terbinafine, and citalopram were detected at more than 1 microgram/L in several wells.
Water samples from the common effluent treatment plant at the industrial estate, which receives process water from approximately 90 bulk drug manufacturers, were found to have very high concentrations of ciprofloxacin and cetirizine often into the milligrams per liter range, even higher than what one would find in the blood of patients taking antibiotics. Very high concentrations of ciprofloxacin, cetirizine, norfloxacin and enoxacin were also detected in two nearby lakes.
Subsequently, in 2015, another study found the polluted lakes harboured considerably high proportions of ciprofloxacin-resistant and sulfamethoxazole-resistant bacteria. It also found multi-resistance plasmids in environmental bacteria that could potentially be transferred to E. coli, a common bacterium responsible for many human infections. While the probability of such transfer is still considered low, the risk increases as the types and abundance of antibiotic resistance genes in the environment go up.
“For too long the pharmaceutical manufacturers have passed on the costs of dealing with negative impact of effluents on poor villagers living around the industrial estates,”
says Babu Rao, a Hyderabad-based scientist and environmental activist.
He also criticized the industry for refusing to invest in more efficient production processes and adoption of green technology and claimed the state pollution control boards did not have the capacity or will to deal with the problem.
Control of manufacturing effluent emissions
In response to growing worldwide concerns about antimicrobial resistance, in 2018, the AMR Industry Alliance, a global coalition of private pharmaceutical manufacturers, developed the Antibiotic Manufacturing Framework to ensure adequate control of manufacturing effluent emissions. Among the measures suggested was calculating API discharge amounts, called the Predicted-No-Effect Concentration (PNEC) or antibiotic concentrations at which, the alliance believes, the selection pressure is minimal on microbes in the environment to mutate and develop drug resistance.
Pharmaceutical companies should not set their own standards
However academics and researchers, working to mitigate antibiotic resistance, have pointed out that pharmaceutical companies are not the right actors to set their own standards. Apart from having an obvious conflict of interest, they also because they lack expertise both in antibiotic resistance and on the environmental impact of pharmaceuticals.
The new standards prescribed by the MoEF&CC are much more stringent than that suggested by the AMR Industry Alliance, with several of them ten times lower. Indian pharmaceutical companies have complained to the Ministry stating they will not be able to comply without shutting production altogether in some cases.
The Indian Drug Manufacturer’s Association (IDMA) said in a letter to the Secretary, MoEF&CC, that it will be technically impossible to monitor levels of individual APIs in units which manufacture multiple APIs and asked for withdrawal of the stipulation till current levels of API in effluents are assessed and technology for their reduction is available. According to the IDMA, there was no technology available currently for achieving the proposed limits and therefore the entire industry would be ‘pushed into non-compliance’.
While agreeing that some of the IDMA suggestions were reasonable Mark Chernaik, an environmental scientist at the US-based non-profit Environmental Law Alliance Worldwide, points out that their call for withdrawing the antibiotic residue limits themselves defeats the central purpose of the notification.
“The antibiotic PNECs should not be the basis for the limits because their purpose is to prevent adverse ecological impacts whereas the notification is meant to prevent the creation of antibiotic resistant pathogens, which is best obtained by reducing the discharge of antibiotics to the lowest level technologically achievable,”
Chernaik said over email in response to a query.
Will global COVID-19 dilute new rules?
Environmental activists fear that, given the current panic over drug supplies being disrupted by the global COVID-19 crisis, the Indian government may either dilute the new rules or postpone their implementation for a long time to come.
A better way may be to not rush and allow more time for wider public discussion on the notification’s merits and shortcomings, taking all points of view on board. This will help come up with options that are both workable and also seriously address the issue of antimicrobial resistance in the long run.
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