drug drain

India’s pharma industry is creating superbugs with its dirty effluent discharges

Major study finds ‘excessively high’ levels of drug residues in water bodies in Hyderabad, allowing microbes to build resistance to medicines.

Industrial pollution from Indian pharmaceutical companies making medicines for nearly all the world’s major drug companies is fuelling the creation of deadly superbugs, suggests new research. Global health authorities have no regulations in place to stop this happening.

A major study published this week in the prestigious scientific journal Infection found “excessively high” levels of antibiotic and antifungal drug residue in water sources in and around a major drug production hub in Hyderabad, as well as high levels of bacteria and fungi resistant to those drugs. Scientists told the Bureau the quantities found meant they believe the drug residues must have originated from pharmaceutical factories.

The presence of drug residues in the natural environment allows the microbes living there to build up resistance to the ingredients in the medicines that are supposed to kill them, turning them into what we call superbugs. The resistant microbes travel easily and have multiplied in huge numbers all over the world, creating a grave public health emergency that is already thought to kill hundreds of thousands of people a year.

When antimicrobial drugs stop working common infections can become fatal, and scientists and public health leaders say the worsening problem of antibiotic resistance (also known as AMR) could reverse half a century of medical progress if the world does not act fast. Yet while policies are being put into place to counter the overuse and misuse of drugs which has propelled the crisis, international regulators are allowing dirty drug production methods to continue unchecked.

Global authorities like the Food and Drug Administration and the European Medicines Agency strictly regulate drug supply chains in terms of drug safety – but environmental standards do not feature in their rulebook. Drug producers must adhere to Good Manufacturing Practices guidelines - but those guidelines do not cover pollution.

Even the World Health Organisation – a global public health body which has repeatedly called for concerted international action to tackle the dangerous threat of antibiotic resistance – buys antibiotics from companies whose drug ingredients are made in Hyderabad without carrying out environmental checks.

The international bodies say the governments of the countries where the drugs are made are the ones responsible for stopping pollution – but domestic legislation is having little impact on the ground, say the study’s authors. The lack of international regulation must be addressed, they argue, highlighting the grave public health threat faced by antibiotic resistance as well as the rampant global spread of superbugs from India, which has become an epicentre of the crisis.

‘Unprecedented antimicrobial drug contamination’

A group of scientists based at the University of Leipzig worked with German journalists to take an in-depth look at pharmaceutical pollution in Hyderabad, where 50% of India’s drug exports are produced. A fifth of the world’s generic drugs are produced in India, with factories based in Hyderabad supplying Big Pharma and public health authorities like World Health Organisation with millions of tons of antibiotics and antifungals each year.

The researchers tested 28 water samples in and around the Patancheru-Bollaram Industrial zone on the outskirts of the city, where more than than 30 drug manufacturing companies supplying nearly all the world’s major drug companies are based. Thousands of tons of pharmaceutical waste are produced by the factories each day, the paper says.

Almost all the samples contained bacteria and fungi resistant to multiple drugs (known as MDR pathogens, the technical name for superbugs). Researchers then tested 16 of the samples for drug residues and found 13 of them were contaminated with antibiotics and antifungals. Previous studies have shown how exposure to antibiotics and antifungals in the environment causes bacteria and fungi to develop immunity to those drugs.

 Antibiotic resistance tests; the bacteria in the culture on the left are sensitive to the antibiotics contained in the white paper discs. The bacteria on the right are resistant to most of the antibiotics. (Dr Graham Beards/Wikimedia Commons)
Antibiotic resistance tests; the bacteria in the culture on the left are sensitive to the antibiotics contained in the white paper discs. The bacteria on the right are resistant to most of the antibiotics. (Dr Graham Beards/Wikimedia Commons)

Environmental pollution and poor management of wastewater in Hyderabad is causing “unprecedented antimicrobial drug contamination” of surrounding water sources, conclude the researchers - contamination which appears to be driving the creation and spread of dangerous superbugs which have spread across the world. Combined with the mass misuse of antibiotics and poor sanitation, superbugs are already having severe consequences in India - an estimated 56,000 newborn babies die from resistant infections there each year.

German broadcaster NDR, which contributed to the study, identified 19 companies operating inside the area tested as suppliers of antibiotics to the European market. Of those 19, the Bureau has identified at least four companies which supply the UK and five which supply the US.

The companies in question strongly deny that their factories pollute the environment, and the sheer number of factories operating in Hyderabad means it is impossible to identify exactly which companies are responsible for the contamination found in the samples tested.

What is clear is one of the world’s biggest drug production hubs is producing dangerous levels of pharmaceutical pollution, and the international bodies tasked with ensuring drug safety are doing little to address it.

Health regulators have to take action, said Professor Ramanan Laxminarayan, director of the Center for Disease Dynamics, Economics & Policy and a leading voice on antibiotic resistance. “We need to take environmental contamination from bulk manufacturing facilities seriously and put an immediate end to the practice,” he said. “This should be a part of GMP without question and pharmaceutical companies throughout the world should be subject to an audit to ensure that they are compliant with what the industry has promised to do.”

The densely populated and increasingly prosperous city of Hyderabad in southern India was once an international trading centre for diamonds and pearls. Today, it is a major international hub for the pharmaceutical and biotech industries, producing millions of tons of medicines, chemicals and pesticides each year.

Around 170 companies making bulk drugs like antibiotics operate in and around Hyderabad, the majority clustered in sprawling industrial estates along the banks of the Musi river. Companies in Europe and the US, as well as health authorities like WHO and the UK’s NHS are reliant on drugs being produced in these factories.

The area has long been criticised for its pollution, which has continued unabated despite decades of campaigning by Indian NGOs, say the report authors. In 2009 the Patancheru-Bollaram zone was classified as “critically polluted” in India’s national pollution index and construction in the area was banned. But the government relaxed the rules in 2014 and building was allowed to begin again.

Last year India’s Supreme Court ordered the country’s pharmaceutical companies to operate a zero liquid waste policy, but “massive violations” have reportedly occurred, says the Infection report.

As India’s drug production industry has grown, so has the prevalence of superbugs – a national crisis intensified by the widespread overuse and misuse of antibiotics, which are easily bought over the counter, and poor sanitation Alongside the creation of individual superbugs, genes and enzymes have developed which can pass between multiple types of bacteria, making them resistant to drugs.

India has become the epicentre of the global drug resistance crisis, with 56,000 newborn Indian babies estimated to die each year from drug-resistant blood infections, and 70% to 90% of people who travel to India returning home with multi-drug-resistant bacteria in their gut, according to the study.

The bacteria can remain in the gut without causing problems, but if they travel from there into a patient’s bloodstream or urinary tract they can cause serious infections. They can also pass on resistance to other bacteria in the gut - so if a patient gets food poisoning the bacteria that caused it could acquire the resistance and become hard to treat.

Highest concentrations

Many previous studies have highlighted pharmaceutical pollution in India and China - which together produce most of the world’s antibiotics – and shown how such pollution fuels the proliferation of superbugs worldwide. The authors of the new Infection study set out to provide a detailed picture of the levels and types of pollution in Hyderabad and its links to drug resistance.

Researchers took water samples from rivers, lakes, groundwater, drinking water and surface water from rural and urban areas in and around the industrial estate, as well as pools near factories and water sources contaminated by sewage treatment plants. Four were taken from taps, one from a borehole, and the remaining 23 were classed as environmental samples.

The samples were tested for bacteria resistant to multiple drugs (known as MDR pathogens, the technical name for superbugs). The researchers then tested 16 of the samples for the antibiotics and antifungals used to treat infections.

All samples apart from one taken from tap water at a four star hotel were found to contain drug-resistant bacteria. All 23 environmental samples contained carbapenemase-producing bacteria - a group of bugs dubbed the “nightmare bacteria” because they are virtually untreatable and kill 40-50% of people whose blood gets infected with them.

Of the 16 samples then tested for drug residue, 13 were found to be contaminated with antibiotics and antifungals, some in disturbingly high levels. The researchers compared the levels of residue to limits recommended by leading microbiologists; once levels exceed those limits it is likely that superbugs will develop.

A sample taken from one sewer contained concentrations of the antifungal drug fluconazole – a drug used in ointments for fungal infections such as thrush and athlete’s foot or given intravenously for more serious infections – at levels 950,000 times higher than the recommended safe limit. The researchers repeatedly analysed this finding to make sure it was correct. “To our knowledge, this is the highest concentration of any drug ever measured in the environment,” wrote the authors.

Samples from sewers in the industrial area were also found to contain “extremely high concentrations” of nine different antibiotics. Levels of moxifloxacin – used to treat lung, skin and sinus infections as well as tuberculosis – were up to 5,500 times higher than the recommended limit, while another common antibiotic ciprofloxacin was found at levels up to 700 times above that recommended. Concentrations of the antibiotics clarithromycin and ampicillin were found at levels more than 100 times higher than the safe limit.

The amounts of antimicrobials found in the new tests were “eye-wateringly high”, said Dr Mark Holmes, a microbiologist at the University of Cambridge. “The quantities involved mean the amount in the water is almost the same as a therapeutic dose,” he said, calling on the Indian authorities to investigate immediately by testing each factory’s effluent. “That’s not just getting rid of a few tablets down the toilet.”

Pharmaceutical pollution is not the only way in which antibiotics get into the Indian environment – excrement from people and animals and waste from hospitals and farms also contain residues of the drugs. But some of the levels detected in the recent testing mean the residues can only have come from bulk manufacturing, according to scientists.

Flamingos at the Ameenpur Lake in Hyderabad. (Sanjeev Verma/HT Photo)
Flamingos at the Ameenpur Lake in Hyderabad. (Sanjeev Verma/HT Photo)

Professor Joakim Larsson, of the University of Gothenburg believes the levels of antimicrobials found could not be explained by anything else other than industrial discharges. “So it tells us that the problem is still there, it needs to be solved,” he told German journalists who worked on the report.

The pharmaceutical industry in Hyderabad produces “enormous amounts” of waste each day, says the Infection report. Effluent is transported in trucks to one waste treatment plant, it says, where it is treated before being sent to a mega sewage plant. There, it is mixed with sewage and further treated then discharged into the nearby Musi river.

Adhering to the zero liquid waste policy ordered by the Supreme Court requires expensive technology, and some waste is still clandestinely sent to the waste treatment plant or dumped straight into the surrounding environment, according to the report.

Virtually all of the world’s major drug companies are supplied by production plants in Hyderabad. Various companies whose factories are located next to or near sites where the water samples were taken supply the US and UK markets, though with such huge amounts of antibiotics present throughout the Indian environment it is impossible to concretely link specific factories to specific test results.

Using the Bulk Drug Manufacturing Industry’s 2015 manual, which lists all Indian drug manufacturers, their locations and their products, journalists at NDR were able to identify 19 companies operating in the Patancheru-Bollaram area which produce the antimicrobial drugs found in the water samples. (There may be other unnamed manufacturers operating in the area or companies which do not advertise which antimicrobials they produce.)

The Bureau has linked a number of these companies to the US and UK markets. MSN Pharmachem is one of the fastest growing drug manufacturers in India. It makes the raw ingredient of the antibiotic moxifloxacin on behalf of international drug companies Macleods and Sun Pharmaceuticals, which then turn it into a finished product supplied to the World Health Organisation.

Other major companies operating in the zone which supply the US and UK markets include Aurobindo, a leading Indian producer which exports to more than 150 countries around the globe, and Mylan, a company which claims its products fill one out of every 13 prescriptions dispensed in America. Mylan also supplies the European Union market, and says it is the fourth biggest supplier of generic (non-branded) drugs in the UK.

The companies strongly refute suggestions that their factories are responsible for pollution.

MSN Pharmachem said it conformed to the highest industry standards, applicable laws and regulations, and operated a zero discharge policy at its factories.

“Our sites are regularly monitored internally and inspected externally,” said a spokesperson. “We are committed to a clean environment, health of all our employees, neighbors, partners and customers.”

Aurobindo said it was impossible any pollution could have originated from its factories as it also operated a zero liquid waste policy – all waste is treated and recycled within the plants. It also said the topography and water flows of the relevant locations meant not even rainwater or drain water would be able to flow from its factories to the sample collection sites.

Mylan also said its factory could not have contributed to the residues identified by the researchers, as all its plants operated a zero liquid waste policy whereby all effluent is recycled and reused on site. It has its own wastewater treatment systems at all its Hyderabad plants, said a spokesperson, which use advanced technology to eliminate harmful waste. “These plants are operated 24 hours a day, seven days a week by qualified individuals,” said the statement.

Macleods and Sun Pharmaceuticals did not respond to requests for comment.

A WHO spokesperson said the organisation did not buy the drug ingredients, just the final medicine, and had no contact with ingredient manufacturers. “Manufacturing sites are typically inspected for Good Manufacturing Practice which focuses on ensuring consistent quality for the product in question from the perspective of human health risk,” said a statement. “GMP does not address waste management and environmental management measures vis-à- vis emissions and pollution control – as here relevant domestic environmental and industrial regulations would apply.”

No mention of pollution

There are reams of regulations and stipulations that manufacturers have to adhere to in order to export their products to the US and Europe – known as the Good Manufacturing Practices framework. These focus on making sure drugs are safe, pure, and effective.

Stringent inspections by the FDA, WHO and European authorities check that these rules are being followed.

However these regulations do not address environmental concerns. Inspectors have no mandate to sanction a factory for polluting, failing to treat its waste or other environmental problems – this falls within the remit of local governments.

Within India, there are environmental regulations covering what ingredients factories are allowed to produce, how they use water and how they dispose of their waste. In Hyderabad, the Telangana State Pollution Board inspects factories based on these.

However these inspection have been labelled toothless by local and international campaign groups. In November 2015, an analysis of TSPCB inspection reports by the Centre for Science and Environment in Delhi found that 15 bulk drug manufacturers within the Patancheru Bollaram industrial area were producing ingredients for which they did not have permission, using more water than the permitted limit, and dumping more effluents and hazardous waste than allowed.

Lots of promises have been made. More than 100 drug companies (including Mylan) signed a declaration at the World Economic Forum in Davos at the beginning of last year pledging to clean up production; commitments which were repeated in an industry roadmap released by 13 major manufacturers in the run-up to the first ever high-level United Nations meeting on antimicrobial resistance last September.

Last week the European Commission also published a roadmap acknowledging the release of antimicrobial ingredients into the environment during manufacture “may pose a risk.” It promised it would explore how to address the challenge in 2018, but fell short of committing to actual policy.

The UK government promised to take action on pollution in NHS supply chains following a previous Bureau report last October, but could not comment on whether this had been followed up due to purdah rules prohibiting any policy announcements in the run-up to an election.

And WHO, along with sister UN agencies, signed a “Statement of Intent” last December aimed at “advancing environmental and socially responsible procurement” of their health products. Just this week, WHO director-general Margaret Chan warned the world was moving towards a “post-antibiotic era” and called once again for concerted global action. She listed actions which were urgently needed, including cutting antibiotic prescriptions, developing new drugs, and coordinated government policies around the world. She did not mention pharmaceutical pollution.

The European Public Health Alliance, an umbrella group for more than 90 non-profit organisations, lambasted the failure of international regulators to do anything about the “rife” pollution which was a “clear cause” of AMR.

“This glaring omission must be rectified by including legally binding environmental standards in GMP protocols, particularly with regard to contamination with antimicrobial substances – as a condition for authorisation and import of drugs,” said a spokesperson. “Voluntary agreements are not enough to stop a race to the bottom, where pharmaceutical companies exploit weak links in global supply chains, in places where there is little or no enforcement of vital environmental standards.”

Tighter regulations on pollution must be introduced, said Dr Yohei Doi, Associate Professor of Medicine at the University of Pittsburgh School of Medicine, and it was up to international buyers of drugs such as the FDA to make this happen. “It’s the buyers in the US that pay for these things,” he said. “As long as people buy these drugs, the companies will keep making them in this way.”

This article was first published on The Bureau of Investigative Journalism.

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Swara Bhasker: Sharp objects has to be on the radar of every woman who is tired of being “nice”

The actress weighs in on what she loves about the show.

This article has been written by award-winning actor Swara Bhasker.

All women growing up in India, South Asia, or anywhere in the world frankly; will remember in some form or the other that gentle girlhood admonishing, “Nice girls don’t do that.” I kept recalling that gently reasoned reproach as I watched Sharp Objects (you can catch it on Hotstar Premium). Adapted from the author of Gone Girl, Gillian Flynn’s debut novel Sharp Objects has been directed by Jean-Marc Vallée, who has my heart since he gave us Big Little Lies. It stars the multiple-Oscar nominee Amy Adams, who delivers a searing performance as Camille Preaker; and Patricia Clarkson, who is magnetic as the dominating and dark Adora Crellin. As an actress myself, it felt great to watch a show driven by its female performers.

The series is woven around a troubled, alcohol-dependent, self-harming, female journalist Camille (single and in her thirties incidentally) who returns to the small town of her birth and childhood, Wind Gap, Missouri, to report on two similarly gruesome murders of teenage girls. While the series is a murder mystery, it equally delves into the psychology, not just of the principal characters, but also of the town, and thus a culture as a whole.

There is a lot that impresses in Sharp Objects — the manner in which the storytelling gently unwraps a plot that is dark, disturbing and shocking, the stellar and crafty control that Jean-Marc Vallée exercises on his narrative, the cinematography that is fluid and still manages to suggest that something sinister lurks within Wind Gap, the editing which keeps this narrative languid yet sharp and consistently evokes a haunting sensation.

Sharp Objects is also liberating (apart from its positive performance on Bechdel parameters) as content — for female actors and for audiences in giving us female centric and female driven shows that do not bear the burden of providing either role-models or even uplifting messages. 

Instead, it presents a world where women are dangerous and dysfunctional but very real — a world where women are neither pure victims, nor pure aggressors. A world where they occupy the grey areas, complex and contradictory as agents in a power play, in which they control some reigns too.

But to me personally, and perhaps to many young women viewers across the world, what makes Sharp Objects particularly impactful, perhaps almost poignant, is the manner in which it unravels the whole idea, the culture, the entire psychology of that childhood admonishment “Nice girls don’t do that.” Sharp Objects explores the sinister and dark possibilities of what the corollary of that thinking could be.

“Nice girls don’t do that.”

“Who does?”

“Bad girls.”

“So I’m a bad girl.”

“You shouldn’t be a bad girl.”

“Why not?”

“Bad girls get in trouble.”

“What trouble? What happens to bad girls?”

“Bad things.”

“What bad things?”

“Very bad things.”

“How bad?”

“Terrible!!!”

“Like what?”

“Like….”

A point the show makes early on is that both the victims of the introductory brutal murders were not your typically nice girly-girls. Camille, the traumatised protagonist carrying a burden from her past was herself not a nice girl. Amma, her deceptive half-sister manipulates the nice girl act to defy her controlling mother. But perhaps the most incisive critique on the whole ‘Be a nice girl’ culture, in fact the whole ‘nice’ culture — nice folks, nice manners, nice homes, nice towns — comes in the form of Adora’s character and the manner in which beneath the whole veneer of nice, a whole town is complicit in damning secrets and not-so-nice acts. At one point early on in the show, Adora tells her firstborn Camille, with whom she has a strained relationship (to put it mildly), “I just want things to be nice with us but maybe I don’t know how..” Interestingly it is this very notion of ‘nice’ that becomes the most oppressive and deceptive experience of young Camille, and later Amma’s growing years.

This ‘Culture of Nice’ is in fact the pervasive ‘Culture of Silence’ that women all over the world, particularly in India, are all too familiar with. 

It takes different forms, but always towards the same goal — to silence the not-so-nice details of what the experiences; sometimes intimate experiences of women might be. This Culture of Silence is propagated from the child’s earliest experience of being parented by society in general. Amongst the values that girls receive in our early years — apart from those of being obedient, dutiful, respectful, homely — we also receive the twin headed Chimera in the form of shame and guilt.

“Have some shame!”

“Oh for shame!”

“Shameless!”

“Shameful!”

“Ashamed.”

“Do not bring shame upon…”

Different phrases in different languages, but always with the same implication. Shameful things happen to girls who are not nice and that brings ‘shame’ on the family or everyone associated with the girl. And nice folks do not talk about these things. Nice folks go on as if nothing has happened.

It is this culture of silence that women across the world today, are calling out in many different ways. Whether it is the #MeToo movement or a show like Sharp Objects; or on a lighter and happier note, even a film like Veere Di Wedding punctures this culture of silence, quite simply by refusing to be silenced and saying the not-nice things, or depicting the so called ‘unspeakable’ things that could happen to girls. By talking about the unspeakable, you rob it of the power to shame you; you disallow the ‘Culture of Nice’ to erase your experience. You stand up for yourself and you build your own identity.

And this to me is the most liberating aspect of being an actor, and even just a girl at a time when shows like Sharp Objects and Big Little Lies (another great show on Hotstar Premium), and films like Veere Di Wedding and Anaarkali Of Aarah are being made.

The next time I hear someone say, “Nice girls don’t do that!”, I know what I’m going to say — I don’t give a shit about nice. I’m just a girl! And that’s okay!

Swara is a an award winning actor of the Hindi film industry. Her last few films, including Veere Di Wedding, Anaarkali of Aaraah and Nil Battey Sannata have earned her both critical and commercial success. Swara is an occasional writer of articles and opinion pieces. The occasions are frequent :).

Watch the trailer of Sharp Objects here:

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This article was published by the Scroll marketing team with Swara Bhasker on behalf of Hotstar Premium and not by the Scroll editorial team.