Cough medicine tainted with ethylene glycol that killed at least 19 children in Uzbekistan in late December 2022 has once again revealed lax oversight and regulation of pharmaceutical companies based in India.
That preventable tragedy, which involves products made by Marion Biotech, based in Noida, India, echoes earlier cases. In the summer of 2022, at least 70 children in Gambia died from kidney failure after using cough medicine made by India-based Maiden Pharmaceuticals that contained ethylene glycol and diethylene glycol, toxic chemicals often used in manufacturing as dissolving agents that can damage the heart, brain, and kidneys.
India has had plenty of time to learn about — and control — tainted drugs, but hasn’t done so. The outbreak in Gambia became public just days after a new book, “The Truth Pill: The Myth of Drug Regulation in India,” was published. The book, written by Dinesh S. Thakur, a former pharmaceutical executive whose revelations of fraud led to a huge and successful U.S. Department of Justice lawsuit against Indian drugmaker Ranbaxy in 2013, and his colleague Prashant Reddy T, a lawyer specializing in intellectual property and drug regulatory law, opens with descriptions of five previous episodes of people dying after using cough medicine.
I spoke with Thakur and Reddy about what ails drug regulation in India, and why it needs to be fixed. Our conversation has been lightly edited for length and clarity.
How common is the problem of ineffective or unsafe or dangerous drugs being made by Indian pharmaceutical companies?
Thakur: It is far more common than it should be. We wrote about five episodes of deaths due to poisoning by medicines made with diethyl glycol that go back as far as 1972. At least 90 people, mostly children, died, though that is certainly an underestimate because this type of poisoning can be difficult to diagnose. All of these were reported to drug regulators, but it kept happening. And it goes beyond cough syrup made with diethylene or ethylene glycol: An adulterated batch of propofol, a sedative used in surgery, killed five people at a hospital in Chandigarh, a city in north India. During the pandemic there was a confirmed news report of generic Remdesivir manufactured by an Indian pharmaceutical company that tested positive for bacterial endotoxins.
Unsafe drugs are just the tip of the iceberg. Substandard or ineffective drugs may be an even bigger problem.
Reddy: India has come to be known as the pharmacy for the developing world. Some of the drugs it makes are used in India or sold to well-regulated markets in the United States and European Union. But India exports a high volume of drugs, mainly generic drugs, to poorly regulated markets in Southeast Asia, Africa, and Latin America. Few of these countries can send inspectors to Indian manufacturing plants to ensure that their processes are safe, or don’t have the resources to test batches of drugs when they arrive in their countries, things the U.S. and Europe can do. So those countries are completely dependent on Indian drug regulators doing their job. If they don’t do their job, people can die.
Is this a difficult problem to stop?
Thakur: It shouldn’t be. The first mass poisoning with diethylene glycol occurred in the United States in 1937 with a “wonder drug” antibiotic called sulfanilamide, made by a U.S. company called S.E. Massengill. The first deaths were reported within a few days of the drug entering the market and, despite a frantic recall, 105 people died. That episode provoked an overhaul of the Federal Food, Drug, and Cosmetics Act with an increased focus on safety. The U.S. has not experienced another mass poisoning with DEG since.
But the same thing hasn’t happened in India because of how the system of oversight was set up, and how it has been managed since.
Reddy: In the U.S., there is a single regulator: the U.S. Food and Drug Administration. It is responsible for overseeing the development and approval of new drugs, and making sure that all drugs are manufactured properly. Its oversight even extends to manufacturing plants in India and elsewhere that are making medicines for the U.S. market. In contrast, India has multiple regulators. The Central Drugs Standard Control Organisation, which is part of the Ministry of Health, is charged with approving new medicines. But once a drug has been approved, oversight of its manufacturing — and the decision to approve generic versions — is in the hands of the regulator in each of India’s 28 states.
After a new drug has been on the market for four years, any competitor can apply to any state in India for a license to make a generic version. Once the application has been approved by the state, the company is good to go. If the product fails testing in a different state, drug inspectors in that state can initiate criminal prosecution of the company, but they cannot inspect the company’s manufacturing facility without the permission and cooperation of the state that licensed the facility.
In other words, India has a system that is fragmented and unwieldy, in which different parts of the regulatory framework are not cooperating, and talking to each other, or sharing information. The country doesn’t even have a simple database of all the drugs that have been approved by different states.
You wrote that “The Government of India is more interested in propping up the Indian pharmaceutical industry — the only manufacturing success story for India to showcase on the global stage — and toward this end it will always resist tightening the regulatory screws.” That’s a pretty bleak view.
Thakur: And it’s unfortunate, because if the pharma industry in India did the right things — making good manufacturing processes part of the standard way to do business, inspecting manufacturing plants, and prosecuting wrongdoers — it has the potential to grow ten times larger.
It sounds like a three-pronged problem: difficult or nonexistent regulation; bad actors, people who are cutting corners and not using good manufacturing processes; and failure to investigate or prosecute. Can you elaborate on the latter?
Thakur: Here’s an example: In 2013, the Drug Testing Laboratory in Chennai found that pills that were supposed to contain glipizide, used to treat diabetes, did not contain that drug but another diabetes drug, glibenclamide, which should not be used as a substitute for glipizide without advice from a doctor. More than half a million tablets had been sold to a government company responsible for buying and distributing drugs to government-run hospitals across the state of Tamil Nadu. It is possible that the substitution was intentional, since glipizide costs four times more than glibenclamide.
A criminal complaint was filed against that manufacturer, Alfred Berg & Company, in 2014. Yet according to our research, as of March 2022, the case had not proceeded to trial despite the court having issued non-bailable warrants for the arrest of the executives in charge of managing the company. It is the responsibility of the state police to execute the warrants. For some reason, not known to us, the warrants were yet to be executed as of 2022.
Reddy: The relationship between the Indian pharma industry, regulators, and prosecutors is a telling example of regulatory capture — when regulatory agencies have come to be dominated by the industries or interests they are charged with regulating. When the system refuses to enforce the law, and the message to the industry and regulators is “Let’s not prosecute these kinds of cases,” that sends a signal that the regulator is more interested in the growth of the pharma industry than in protecting public health.
What prompted you to write “The Truth Pill?”
Thakur: After the Ranbaxy settlement in 2013, there was some attention on the Indian pharma industry, both globally and nationally. But then regulators and prosecutors went back to what they had been doing before that. So we worked for more than a year to put together what we thought was a meaningful pathway for reforming drug regulation in India. We brought it to the Minister of Health, but it didn’t go anywhere.
We then tried a different approach: In India, an individual or group can file a petition on behalf of the public as long as those filing would not personally benefit from a resolution of the situation. The judges who reluctantly heard our public interest litigation called it an “academic issue” and forced us to withdraw the petition.
Because people in India, and those in countries receiving pharmaceuticals made in India, don’t understand the magnitude of the problem — rightly so, because there’s been little reporting or academic writing on this issue in India — we decided it would be a good idea to put our research into a book and put it out there so there’s a more informed public conversation on some of the issues that needed to be fixed.
Given how protective India appears to be of its pharmaceutical industry, what’s it been like since you published the book?
Reddy: The government hasn’t spoken about the book, but it didn’t appreciate what we said after the deaths in Gambia became news. We made some statements in an interview to the press that were critical of the national regulator — the Central Drugs Standard Control Organisation — and the Ministry of Health, which also plays a big role in drug regulation.
In response, we received a menacing legal notice from the national drug regulator on a Saturday evening, 30 minutes before our book was set to launch in Delhi. It was not clear about what law we had violated, but threatened us with undermining “trust and faith of the public in the Indian Drug Regulatory system” — which isn’t a crime.
Thakur: It’s a page right out of their playbook. A few years ago, Amir Attaran, a professor of law and medicine at the University of Ottawa, and several colleagues conducted a study on the quality of India-made antibiotic and tuberculosis drugs sold in Africa, India, and five mid-income countries outside of Africa. They established that Indian companies sold poorer-quality medicines in Africa than in other countries. The government of India threatened to sue the authors and their funders for defamation.
The same thing happened when Katherine Eban’s exposé of India’s generic drug industry, “Bottle of Lies,” was published. The national regulator wrote to the Ministry of Health, asking it to take legal action against Eban.
Instead of trying to solve the problem, the government’s first reaction is, “How do you shut these people up?”
Say next week you get a call from Narendra Modi, India’s prime minister, asking you two to revamp drug regulation in India. Where would you start?
Thakur: The first and easiest thing we would recommend is transparency. Make the functioning of the Central Drugs Standard Control Organisation and all state drug controllers more transparent. Publish all inspection reports of pharmaceutical manufacturers within 30 days of the inspection. Publish detailed minutes of meetings of all statutory and advisory committees on any drug approval or licensing public within a few weeks. Create a national database of all regulatory actions taken against every pharmaceutical manufacturer and make it public. That would be an excellent start.