Poisoned Cough Syrup Killed Kids. Authorities Cut the Investigation Short
Views:
1970-01-01 08:00
This is the first installment of Bad Medicine, a series about how porous regulation and cheap drugs are

This is the first installment of Bad Medicine, a series about how porous regulation and cheap drugs are endangering lives around the world.Ebrima Sagnia was frantic as he carried his son through the doors of a hospital one evening last September. A few days earlier, Lamin had been a rambunctious 3-year-old, chasing a ball around the yard. Now he was listless and unable to speak.

Staff at the Edward Francis Small Teaching Hospital in the tiny West African nation of Gambia recognized the symptoms at once. They weren’t surprised to learn that Sagnia had given his son a few doses of cough syrup, just as thousands of parents around the world do every day.

A doctor snatched the bottle from Sagnia. “All these children lying here, they all took the same medication,” he said. Sagnia looked around. There were four or five other children in the emergency pediatric ward, too ill to eat or sit up. Most of them, like Lamin, would be dead within a week.

The outbreak last summer would eventually kill more than 60 children in Gambia, most of them even younger than Lamin. Tests arranged by the World Health Organization confirmed the hospital staff’s suspicions: Four varieties of cheap, common, over-the-counter syrups meant to treat coughs, colds and nausea were loaded with toxic industrial solvents that can ravage internal organs. A few teaspoons, ladled into a kid’s mouth to help him sleep through the night, was a death sentence.

The syrups had been made in India by a company called Maiden Pharmaceuticals Ltd. In early October, after the WHO sent an urgent communique to India’s national drug agency, inspectors raided the company’s factory on the outskirts of Delhi and determined that it hadn’t been testing its raw materials for contamination as required.

That should have been the first step in a wide-ranging investigation. Somewhere in the country’s chaotic chemical supply chain, someone had replaced a harmless compound used in making syrups with a cheaper, deadly one. There was no telling how many other drugmakers were using the same counterfeit supplies. In fact, by the time of the raid on the Maiden plant, a factory across town had been unwittingly making drugs laced with the same poison for more than a year. But instead of tracking down the rogue suppliers and rooting out contamination, Indian authorities cut the probe short.

They declared that the syrups made in India had nothing to do with the deaths of Lamin Sagnia or any of the other children in Gambia. The factory across town would continue making poisonous drugs. And thousands of miles from Gambia, more frantic parents would soon start showing up at a hospital, carrying dying children in their arms.

India calls itself the “pharmacy of the world.” Over the past few decades, its cheap generic exports have undercut Western brands and made inroads in developing countries, ushering in a global era for pharmaceuticals. Today, about one-fifth of the generic drugs consumed in the world come from India. In Africa, it’s half. For Narendra Modi, the country’s nationalist prime minister, the booming $50 billion industry is a source of national pride and an economic muscle to flex on the international stage.

The global market promises better access to healthcare for the world’s poor — along with new risks. From cough syrup to eyedrops to life-saving medications, quality lapses in one country can now endanger lives elsewhere as never before, even in developed countries. The WHO, an arm of the United Nations, can advise and cajole, but it cannot force national governments to improve their standards. And local regulators are often ill-prepared or unwilling to deal with problems that cross national borders. Rarely have these risks been on display as starkly as they were last year when Indian authorities responded to the outbreak in Gambia.

Two days after getting word from the WHO linking the deaths in Africa to Maiden, inspectors from India’s national drug agency, the Central Drugs Standard Control Organisation, made their way through an aging industrial park north of Delhi. In rows of concrete buildings there, workers churn out shoes, grease, car parts and powdered milk. Cows pick through piles of trash on the roadside, and women wash dishes where an open tap pours onto the ground. Arriving at Plot 81, the inspectors passed a rusty blue gate and stepped inside.

Healthcare watchdog groups and some former regulators say India’s drug regulatory system is set up to promote the industry rather than police it. They say coordination is often lacking between the national drug agency and more than 30 local ones, and that there aren’t enough inspectors for the country’s 3,000 drugmakers and 10,000 factories. Even when quality problems are found, they say, consequences are minimal.

That certainly was the case at Maiden, which repeatedly failed quality tests in the years leading up to the Gambia outbreak. One substandard-drugs case dragged through India’s sclerotic courts for nine years before being dismissed on a technicality. Another took 12 years and resulted in a fine of 1,000 rupees, or about $15 at the time. Maiden specializes in exporting to some of the smallest emerging markets, where prices are low and regulation is light. Despite the quality problems, customers in places like Afghanistan, Iraq and Venezuela kept buying.

Maiden’s founder, Naresh Goyal, worked his way up as a sales rep and a distributor before building a plant of his own, says his son Manish. “He did everything from scratch, by himself.”

Goyal wasn’t above cutting the occasional corner. Once, he tried to sell a pill called Mcalis, bearing an uncanny resemblance to the American-made erectile-dysfunction drug Cialis. It even had the same distinctive swirl engraved on each tablet. Ordering Maiden to stop, a New Delhi judge in 2009 said the firm had been called a “habitual infringer” of brand names. Goyal and Maiden did not respond to calls, emails and personal visits requesting comment for this story.

By the time the inspectors showed up at Plot 81, Goyal was prospering. He had moved his extended family into a four-story home in one of Delhi’s toniest enclaves, where a shiny chrome sign on a wall outside reads “Goyal’s Mansion.” It was a different picture inside the factory. Inspectors found a paperwork mess. Key records were missing and others were contradictory, according to a regulatory notice seen by Bloomberg News. Among other things, there were wildly conflicting dates for when the Gambia drugs had been formulated.

This paper trail was critical because of the way liquid medication is made. Syrups consist of active ingredients, such as the cough suppressant dextromethorphan, suspended in a watery solution. By themselves, those ingredients would just settle to the bottom of the bottle. So manufacturers add a solvent. Often, that’s propylene glycol, a harmless, clear, slightly sweet liquid derived from petroleum.

That’s where the trouble starts. Two other widely available chemicals, ethylene glycol and diethylene glycol, look and taste like propylene glycol. They have the same solvent properties but are much less expensive. They are also toxic in small doses, especially to children whose low body weight makes them more vulnerable. The medicines sold in Gambia contained both.

Mass deaths from syrup tainted the same way have occurred more than a dozen times in recent decades — in Haiti, Panama, Nigeria, India and elsewhere. But Gambia was the first time imported medicine was involved. In the earlier cases, the adulteration often happened when a chemical trader sold the toxic substances mislabeled as propylene glycol and a careless manufacturer failed to check for contaminants. After reviewing the records, the inspectors concluded that Maiden had not been conducting these lab tests, the notice shows. They ordered the plant temporarily shut.

The next step, if Indian authorities had followed the playbook used by regulators elsewhere, would have been to trace the bad chemicals to their source. Only then could they chart the full extent of the outbreak and identify any other drugs that might be poisoned.

Four days after inspectors visited Maiden, the WHO made a public statement linking the deaths in Africa to Indian drugs. The news was picked up around the world, and TV cameras swarmed the plant. There were calls for reforms of the Indian drug control system. When asked for comment, the health ministry said the drugs hadn’t been authorized to be sold in India, only abroad. And it pointed a finger back at Gambia. “It is a usual practice,” the ministry said, “that the importing country tests these imported products on quality parameters.”

Modi’s government is prickly about foreign criticism, particularly when it comes to the pharmaceutical industry. Officials there know how Western pharma giants sometimes use quality concerns as a pretext to fend off Indian rivals and preserve high prices. That happened most memorably in the early 2000s, when Indian companies sent the first cheap AIDS drugs to Africa, defying Western patents and saving millions of lives.

The Maiden investigation soon took some odd turns. Inspectors had seized drug samples from the plant, but months went by without any word of test results. A high-level committee appointed to look into the matter started second-guessing Gambian officials’ conclusions, demanding reams of medical records on each of the dead children.

The WHO, which tries to coordinate cross-border inquiries about bad drugs, pressed V.G. Somani, the Indian drug controller general, for updates on the source of the chemicals. Rutendo Kuwana, who heads the WHO team that tracks bad medicine around the world, says it’s crucial for regulators to share information rapidly. “If we follow the money, we follow the supply, we’ll be able to say which countries are directly impacted, and we stop it before it gets out of hand,” Kuwana says. But his team waited months for a meaningful response.

Finally, in December, Somani sent a defiant letter to the WHO that found its way to Indian newspapers. India, he wrote, had done its own testing of the Maiden drugs and found them to be free of contamination. Any link between the deaths and India, he said, was a “premature deduction” now disproven.

Somani, who declined to comment for this story, went on to complain of “a narrative being built internationally targeting the quality of Indian pharmaceutical products.” He wrote that this “has adversely impacted the image of India’s pharmaceutical products across the globe and caused irreparable damage to the supply chain of pharmaceutical products.”

Among health officials outside India, there was little doubt about the cause of the outbreak. The Maiden drugs were shown to be tainted in separate tests by three independent laboratories, and kids stopped dying as soon as the products were taken off the market. It was particularly ironic that the denial was coming from Somani. He had served for three years as chairman of a WHO forum for international cooperation on substandard medicines. Now he was blocking the way.

Somani treated the test results as the final word on Maiden, but his inspectors didn’t test the same bottles the WHO did — those taken from the families of sick children in Gambia. Instead, they seized samples from the Maiden plant that were labeled as being from the same batches. And they delayed their visit for two days, creating a window of opportunity for anyone who wanted to switch the bottles.

In his letter, Somani dropped a clue about the origin of the chemicals used in the Gambia drugs. He said Maiden had gotten its propylene glycol from a dealer in Delhi and that the material had been manufactured by SKC Co., a leading South Korean chemical maker.

Acting on that clue, the WHO passed the word to the Korean drug ministry, which visited SKC’s plant and conducted an audit looking back two years. The review found nothing amiss, according to Joe Guy Collier, an SKC spokesman, as well as a person outside the company with knowledge of the matter who spoke on condition of anonymity. The ministry declined to comment. It’s chemically impossible for the plant’s “catalyst-free” propylene glycol manufacturing process to generate the contaminants found in Gambia, Collier said in an email.

In all likelihood, Collier said, someone put a fake product in an empty SKC barrel. But with the Indian government claiming there was nothing wrong with the chemicals in the first place, the prospect of tracking down the source of the contamination looked dim.

The idea that someone might slip a deadly poison into the global drug supply seems ghastly. Among people in India’s shambolic chemical marketplace, it’s greeted with a shrug.

“Chemical is one thing which cannot be sold on Amazon or Flipkart, right?” says Pankaj Mehra, a chemicals trader whose family has been in the business since 1951. He’s sitting behind a desk in a dimly lit basement office in North Delhi, explaining to a couple of visitors the convoluted path that propylene glycol takes to a small Indian drugmaker’s door. Every few minutes, Mehra’s mobile phone bleats and glows, and a rapid-fire negotiation ensues, hopscotching between Hindi and English, over how many drums for how many rupees.

Propylene glycol has an astonishing array of uses. You probably ate, inhaled, or touched some today. It gives lipstick its peculiar consistency, makes shampoo foam and strengthens pizza dough. It is used to make the hulls of fishing boats. It keeps cigars moist and paint brushes wet. Farmers pour it down the throats of sick cows. It is used in vape cartridges, breweries and skating rinks.

Most of the propylene glycol in India comes from China, Southeast Asia and the Middle East. As Mehra explains, chemical makers and importers deal only with large orders, so it falls to a complex chain of middlemen — some licensed to handle pharmaceutical-grade products, some not — to break shipments into progressively smaller quantities. A chemical might pass through several dealers’ hands before reaching a buyer as small as Maiden.

With deadly diethylene glycol selling for about half the price of propylene glycol, Mehra says, the temptation to mislabel or dilute is always present. Adulteration is so commonplace, he says, that empty chemical drums with intact labels fetch a premium over bare ones because counterfeiters can re-use the labels. “Unfortunately, there are some creatures who just want to make money,” Mehra says, “and that too at the cost of somebody’s health.”

An example of how that happens came to light last year in Indonesia, after about 200 children died from swallowing poisoned medicine. The chief of the nation’s drug agency, Penny Lukito, convened a press conference in a muddy yard outside a warehouse stacked with rusty drums. She announced that the building’s owner, a small-time chemical dealer, had been selling phony propylene glycol. The material went from there to other traders and into syrups made by at least four local drugmakers, even though the labels on the drums misspelled the name of the purported manufacturer as “Dow Chemmical.”

A shortage of propylene glycol may have played a role in the Indonesia case, giving an opening for the unlicensed supplier, Lukito told a local newspaper. But the market disruptions weren’t limited to Indonesia. They swept across the world in 2020 and 2021. In India, propylene glycol prices more than tripled in the first half of 2021, according to Karan Chechi, research director at ChemAnalyst, a global market intelligence firm based near Delhi. Covid-related plant shutdowns crimped Chinese supply, while a winter storm shuttered Texas refineries. “The market was so much in shortage that people were literally dying for it,” Chechi says. “They were ready to procure anything — whoever called it PG, they literally bought it.”

Mehra scoffs at the memory of that price spike, blaming it on greedy chemical makers and their “so-called MBA culture.” He says he can’t point to anyone specifically who dealt in phony products. But in the past few years, he says, word has circulated in the chemical market that something fishy was going on with drums labeled as coming from SKC — the same company whose barrels were thought to be used in the Gambia medicines. “There is a lot of material coming in as SKC which is not authentic at all,” Mehra says. “Say, 100 metric ton is coming in from abroad, and 120 metric ton is being sold. How is it possible?” Someone, he suspects, is putting fake SKC drums on the street.

Late last year, at the same time India was declaring Maiden blameless in the Gambia poisonings, events unfolding in another part of the world put the episode in a different light. Physicians at a hospital in Samarkand, Uzbekistan, noticed a number of children developing severe kidney problems. The death toll would eventually climb to about 20. Uzbek authorities traced the problem to imported cough syrups made by another Delhi-area manufacturer, Marion Biotech Pvt. Ltd.

The news put Somani, the Indian drug controller general, in an awkward position. It would be difficult to deny responsibility for a second outbreak so soon after the first. This time, his investigators moved aggressively. They raided the Marion factory, confirmed the drugs were loaded with poison and canceled the company’s manufacturing license. Marion told Bloomberg in January that it complied with drugmaking rules and was cooperating with authorities. It did not respond to subsequent requests for comment.

Scouring the Marion plant, investigators found a container labeled propylene glycol that turned out not to be propylene glycol at all — it consisted mostly of the highly toxic ethylene glycol. They determined that Marion had been making poisoned drugs for at least a year and a half, and that it had been getting most of its supply from a small trader called Maya Chemtech India Pvt. Ltd. Drugmakers aren’t supposed to buy from Maya, which doesn’t have a license to sell pharmaceutical supplies. But Maya’s website has openly solicited their business. One page showed a row of white steel drums labeled as pharmaceutical-grade propylene glycol, each bearing the distinctive butterfly logo of SKC.

In addition to supplying Marion, Maya was also, indirectly, supplying propylene glycol to Maiden, the maker of the Gambia syrups, according to two Indian drug officials who asked not to be identified because they weren’t authorized to discuss the matter. Maya had been selling to Goel Pharma Chem, a nearby Delhi trader which in turn sold to Maiden, these people say. If their account is correct, inspectors probing the Maiden case in early October may have missed a chance to identify Maya’s other customers, a step that could have led them to the tainted drugs in Uzbekistan before they proved deadly.

Goel’s proprietor, Sharad Goel, did not respond to inquiries from Bloomberg and has given conflicting accounts to others. He told Reuters in February that he got the chemicals from an importer in Mumbai he would not name. Months earlier, India’s Tribune newspaper reported that Goel’s firm told investigators the material came from “another Delhi trader.” SKC, the Korean manufacturer, says it never sold directly to any of the companies involved.

Perhaps the crucial clues that would unravel both cases lay in Maya’s warehouse on the ground floor of a two-story concrete building on a dusty side street in North Delhi. Was it possible that all the poison passed through its gates on its way to children’s bellies in Central Asia and Africa? Even if no one at Maya knowingly sold fake chemicals, the firm could be a key link in the chain leading back to the perpetrator.

But no evidence has emerged that Indian officials went any further in their investigation, identified anyone who faked chemicals or tracked down other drugmakers that might have bought from Maya. There was no press conference in a muddy courtyard. In March, the drug agency issued an alert telling pharmaceutical companies not to buy propylene glycol from Maya, something they were already not allowed to do.

One of the drug officials who spoke on condition of anonymity says that the authorities’ hands were tied. Inspectors didn’t find any pharma-grade propylene glycol when they visited the warehouse, so Maya was allowed to remain in business. It is impossible, the official adds, to monitor the supply of chemicals in India.

Maya’s proprietor, Baljeet Verma, works out of an office nearby and operates chemical businesses under a number of different names. He did not reply to calls or emails. When reporters showed up in April to try to speak with him, he covered his face with a Covid mask and slipped out without answering questions.

At the Maya warehouse, black soot marks trail up the walls above a padlocked entrance. Neighbors say a fire tore through the place one evening in March, a couple of days after the agency’s alert, and that they didn’t know the cause. A glimpse through a shattered window shows the interior was trashed. White chemical powder lies in heaps where plastic sacks had burned away. The eye-stinging stench of ammonia greets anyone passing by.

After Uzbekistan, the bad news about Indian medicines piled up. Indian-made eyedrops laced with bacteria led to the deaths of four Americans. Officials in Cameroon said a cough syrup bearing the license number of an Indian manufacturer was suspected of killing a dozen children, and poisoned syrup from other Indian companies was found circulating in the Marshall Islands and Liberia, although no deaths were reported there. The WHO said it’s exploring whether pandemic-era gyrations in the propylene glycol market might explain the spate of cases.

In February, India’s health ministry replaced Somani, the drug controller general. His successor pushed through a rule requiring that all cough syrups be tested for contamination at a government lab before export, and he took action against dozens of manufacturers for quality lapses. The moves were calculated to reassure foreign customers that Indian drugs could be trusted.

Public-health watchdogs are skeptical. Depending on how officials interpret “cough syrup,” the new rule may not even cover all risky syrup exports, many of which treat other conditions, says Malini Aisola of the All India Drug Action Network. Nor would the rule help consumers in India, where 13 children died after a similar outbreak in 2020.

“This is just an eyewash to cover up the bad PR,” says Dinesh Thakur, a drug-industry whistleblower and co-author of a book about quality lapses. Instead of doing more testing, he says, the government should overhaul its antiquated drug law, boost enforcement of good manufacturing practices and reform the Balkanized system of local licensing. “Rather than addressing systemic issues with our drug regulation and enforcement, all they do time and time again is to cover up their incompetence.”

Officials continue to insist that Maiden’s drugs were untainted. In February, a judge sentenced Goyal, the Maiden founder, to two and a half years in prison — not for the Gambia poisonings, but for a nine-year-old allegation involving antacid pills that didn’t meet specifications. He was allowed to post bail pending appeal. In a handful of comments to media organizations, Goyal has insisted his company did nothing wrong, at one point blaming the Gambian deaths on French imports or a bacterial infection. As recently as April, he was still trying to get permission to restart his plant.

The health ministry and the drug controller general’s office did not respond to detailed questions from Bloomberg. “We want to assure everyone that we are the ‘quality pharmacy of the world,’” Health Minister Mansukh Mandaviya told India’s PTI news agency last month. “India will never do any bargain with the quality of medicines. We follow a zero-tolerance policy.”

Modi’s strident nationalism continues to loom over the scandal. His health minister, Mansukh Mandaviya, has spoken darkly of “an attempt to tarnish India’s image.” In interviews in Delhi, people in the drug trade take Maiden’s blamelessness as a given, although specific theories vary. Bal Kishan Gupta, a regional vice president at the Indian Drug Manufacturers Association, suggests his country has somehow been framed by a foreign power. “Indian people never do such things, but Chinese are capable of doing that,” he says. “Every possibility should be looked into.”

Even after the consensus had hardened in India, Maiden’s drugs weren’t done killing. On New Year’s Day, 4-year-old Isha Darboe died at the Edward Francis Small hospital in Gambia. She’d been dosed from a bottle of anti-nausea syrup that had somehow escaped the recall. Her father, Lamin Darboe, says he had heard about bad medicine circulating in the country, but a woman at the pharmacy had assured him this one was fine.

At his home in a fishing village on the Atlantic coast, Darboe lights a cigarette and scrolls through photos on his phone. There are dozens of Isha — showing off new dresses, posing with her younger brother, sticking her tongue out for the camera. She had been looking forward to starting school this year when she would have turned 5. He tears up when he recalls her final days in the hospital. Too weak to speak, she communicated with her father mostly by pinching him, he says. “She was dying in pain.”

He scrolls to another snapshot: a picture of the box of Maiden drugs that killed his daughter, an “M” logo indicating its maker. The liquid in the 100-milliliter bottle had completed an astonishing odyssey made possible by the pharmacy of the world, crossing seas and oceans to wind up in Isha Darboe’s mouth. National borders meant nothing — until it came time to determine what went wrong.

--With assistance from Kendall Taggart, Heejin Kim, Nariman Gizitdinov, Chandra Asmara, Eko Listiyorini and Shruti Mahajan.

Author: Zachary Mider, Swati Gupta and Modou Joof

Tags conss coronavir govtop hea cmd africa alltop basic asiatop gen drg 011790 ks cos 0751538dsw cons business gentop gov chm asia