The FDA Hasn’t Inspected This Drug Factory After 7 Recalls for the Same Flaw, 1 Potentially Deadly

https://www.propublica.org/article/glenmark-pharmaceuticals-recalls-fda-oversight

Reporting Highlights

• Flawed Drugs: Indian drugmaker Glenmark Pharmaceuticals issued a string of recalls for pills that didn’t dissolve properly. In one case, the company said the problem could be deadly.
• Anemic Response: Since the recalls, the FDA still hasn’t visited the factory in India that manufactured the drugs or stopped Glenmark from shipping other drugs made there to the U.S.
• Death Reports: Glenmark got reports of three deaths of patients who took the recalled pills. The cause is unclear. A lawsuit alleges the pills killed a Maine woman. Glenmark denies it.

The drug potassium chloride has been on the market for decades, widely prescribed to help the nerves and muscles — including the heart — function properly in patients with low potassium. Too much of it, however, can kill you.

At high doses, it is so effective at stopping the heart that some states have used injections of it for executions.

So the danger was obvious in May, when Indian drugmaker Glenmark Pharmaceuticals recalled nearly 47 million capsules for a dire flaw: The extended-release medication wasn’t dissolving properly, a defect that could lead to a perilous spike in potassium. The U.S. Food and Drug Administration deemed it the most serious kind of recall, a defective drug that had the potential to kill people.

At the time of the recall, the FDA, which is charged with protecting Americans from unsafe drugs, was already on notice about troubles at Glenmark.

The Mumbai-based company had four recalls in the previous eight months and would have two more in following months, all for the same dangerous tendency for pills to dissolve improperly. All the faulty medications were made at the same Glenmark factory in central India, government records show.

Yet the FDA hasn’t stopped Glenmark from shipping pills from the factory to American patients. Nor did it send investigators to the Indian facility to figure out what had gone wrong. Its last inspection of the plant was more than four years ago, before the COVID-19 pandemic.

“They should have been camping out there,” said Patrick Stone, a former FDA inspector who now advises pharmaceutical companies.

Since the May recall, Glenmark told regulators it has received reports of three deaths, three hospitalizations and four other serious problems in patients who took the recalled potassium chloride capsules, FDA records show. It’s unclear if the drug was the cause.

A federal lawsuit alleges that the pills were responsible for the death of Mary Louise Cormier, a 91-year-old woman in Maine. A letter informing her of the recall arrived three weeks after she died.

The FDA’s anemic response underscores longstanding weaknesses in the way the agency oversees the safety of generic medications manufactured in foreign factories. The agency failed to act on clear patterns of trouble, was slow to warn the public about the potentially deadly pills and never mentioned that millions of them had been sold to consumers.

From the day of the first recall in October 2023 through the next 12 months, the FDA oversaw 22 recalls for drugs that didn’t dissolve correctly and could cause harm, agency data shows. That single Glenmark factory was responsible for more than 30%, a ProPublica analysis found.

“The FDA is always late to respond,” Stone said. “This should have been dealt with immediately.”

The FDA has long said it polices foreign plants by prioritizing inspections based on risk. For routine inspections, the agency uses a computer model that weighs prior recalls, the date and results of the most recent inspection, and other factors. FDA employees decide when to send investigators for more urgent visits based on signs that something is amiss. But the agency would not explain why Glenmark’s string of recalls didn’t meet that threshold.

What’s more, federal regulators were aware of significant deficiencies at three of Glenmark’s four other factories that have made drugs for the U.S. market, FDA records show. The breakdowns were so grave at one plant that the FDA barred drugs made there from entering the country.

The FDA’s failings date back decades. In her book “Bottle of Lies,” journalist Katherine Eban exposed the agency’s struggles to identify and combat corruption in the global pharmaceutical industry amid a huge demand for cheap generic drugs in the U.S. The book detailed how a whistleblower in 2005 started feeding the FDA insider details about unsafe medications at a different Indian drugmaker, but it took federal officials almost nine years to wrap up a criminal case.

The majority of the factories making drugs for U.S. patients are in other countries, many of which churn out the generics that make up more than 90% of prescriptions filled here. Yet the investigative arm of Congress has repeatedly found that the FDA has too few inspectors to adequately oversee these plants.

The consequences of lax oversight were unmistakable when the U.S. Centers for Disease Control and Prevention reported in 2023 that four people died and others had to have their eyeballs removed after they used contaminated eyedrops made by a different Indian company. The FDA had never inspected that factory before people got sick.

Fed up with what they called “institutional weaknesses and dysfunction” in the oversight of foreign drugmakers, the House Committee on Energy and Commerce in June demanded that the head of the FDA turn over documents about inspections in India and China.

A spokesperson for the FDA declined to answer questions about the Glenmark recalls or inspection history, saying the agency could not publicly discuss potential or ongoing compliance matters. “When there are quality issues identified that could result in harm, patients should rest assured that the FDA does everything within our authority to work with firms to ensure a recall is conducted most effectively,” FDA spokesperson Amanda Hils wrote in an email. A recent reorganization, she added, “will ultimately help the agency be more efficient and cohesive in our inspection and investigation efforts.”

Officials with Glenmark also declined to answer detailed questions. In a court document, the company denied being responsible for the death of Cormier, the woman in Maine.

“Due to the ongoing litigation, we are unable to provide further information at this time but Glenmark is fully committed to maintaining the highest standards of quality and regulatory compliance in all our operations,” a Glenmark spokesperson wrote in an email. “We continue to work closely with the FDA to ensure compliance with manufacturing operations and quality systems.”

Overseas compliance with U.S. manufacturing standards is crucial in a drug market where foreign factories like the ones operated by Glenmark make a wide range of injections and pills that treat some of the most vulnerable patients in the U.S., including those with cancer, heart disease, epilepsy and kidney ailments. What happens in a factory a half a world away can have deadly consequences.

Glenmark’s major troubles with the FDA began in 2019 at a factory far from the one that made the potassium chloride.

That spring, FDA investigators went to the company’s Himachal Pradesh plant in northern India and reviewed more than 100 complaints about products made there: A steroid cream was gritty, a medication was watery, and tubes of medicines were cracked and punctured

The inspectors found so many problems at the facility that the agency sent Glenmark what’s known as a warning letter, a disciplinary tool the FDA uses to lay out significant violations of federal requirements and demand changes. Too often, Glenmark didn’t identify the root causes of problems and failed to come up with plans to prevent the same defects in the future, the director of the FDA’s Office of Manufacturing Quality wrote to Glenmark’s chairman.

“Your quality system for investigations is inadequate and does not ensure consistent production of safe and effective products,” the FDA official wrote.

This became a recurrent theme for Glenmark in subsequent years as FDA investigators dinged one plant after another for failing to follow manufacturing processes that prevent defective drugs from winding up in American medicine cabinets.

FDA records show the problems stretched from India to the U.S., where Glenmark has a factory outside of Charlotte, North Carolina. In August 2021, Glenmark recalled every product it made at that plant. The recall notices said they failed to meet manufacturing standards.

In the spring of 2022, FDA investigators spent more than a month in that factory, documenting 17 violations that resulted in a warning letter for that plant as well.

The problems snowballed in the fall of 2022. The FDA sent Glenmark’s chairman yet another warning letter, this time about its factory in Goa, India, which the agency said failed to thoroughly investigate discrepancies among batches of drugs and lacked the procedures necessary to ensure that its products had the strength, quality and purity that Glenmark claimed. And FDA officials were so concerned after a subsequent inspection of Glenmark’s Himachal Pradesh factory that they placed it on the agency’s dreaded import alert list, which allowed federal regulators to prevent drugs made there from entering the U.S.

At that point, three of the five Glenmark factories that had made drugs for American consumers were in trouble with the FDA.

But one plant has escaped scrutiny in the last few years: the Glenmark facility that made the recalled potassium chloride.

The factory, in Madhya Pradesh, India, previously had a mixed record with the FDA. The agency had sent inspectors every year between 2015 and 2020, finding problems in half the visits.

In 2018, the FDA asked Glenmark to voluntarily make improvements after inspectors found evidence that drafts of internal investigations were shredded in the quality department, among other deficiencies.

Subsequent inspections in September 2019 and February 2020, though, went well.

Then the COVID-19 pandemic hit, and the FDA put all but the most urgent inspections on hold. An Associated Press analysis this September found that about 2,000 pharmaceutical plants had not been inspected by the FDA in five years.

The FDA doesn’t have enough experienced investigators to figure out what’s wrong at factories where there are signs of trouble, said Peter Baker, a former FDA inspector who consults on pharmaceutical quality.

“It’s really difficult to be proactive when you don’t have people,” Baker said.

People familiar with FDA enforcement say inspectors are often frustrated because they have little say on which facilities they inspect. That decision is made by another arm of the agency that doesn’t have the same sort of on-the-ground view of what’s going on in factories.

Those who have the most to lose — the patients who could be endangered by defective pills — rarely, if ever, learn about the conditions inside the manufacturing plants. The FDA doesn’t make it easy for people to know where a drug is made, let alone whether it was by a factory with a concerning safety record.

To determine that the recalled Glenmark drugs were all made at the Madhya Pradesh factory, ProPublica matched drug-labeling records from the U.S. National Library of Medicine with details in two FDA databases. Because the FDA doesn’t routinely post its inspection reports online, ProPublica obtained these and other records from Redica Systems, a data analytics company that receives this information from the FDA through public-records requests.

The first in the string of recalls from the plant came in October 2023 for a drug that treats iron overload from blood transfusions. Days later, the company announced a second recall, this time for a medication for chest pain. Then came two more for capsules that treat high blood pressure. The potassium chloride recall was Glenmark’s fifth. Two more came after that, for a cholesterol-lowering drug and a rheumatoid arthritis medicine.

The only one mentioned on the FDA’s recalls website was the potassium chloride. In that case, the agency followed its practice of posting a press release from the drug company rather than writing its own alert for the public.

“Public notification is generally issued when a product poses a serious health hazard or has been widely distributed,” the FDA spokesperson wrote in an email.

Records show the agency determined that potential harm from taking the other pills Glenmark recalled was likely to be temporary or reversible. But it never told the public what that harm might be.

Mary Louise Cormier never knew her potassium chloride pills had been recalled.

On June 27, the 91-year-old was taken to the emergency room from her nursing home in Brunswick, Maine. She was lethargic and could give only soft, monosyllabic answers to questions, according to the lawsuit filed by one of her daughters.

A blood test showed that her potassium level was alarmingly high — so high that an emergency room doctor had the lab run the test a second time to make sure the result wasn’t a mistake, according to the lawsuit. A level above 6 millimoles per liter is considered a medical emergency. The tests showed Cormier’s level was 6.9, the lawsuit says.

Cormier — who had raised five children, cared for babies in the foster care system and once ran a day care out of her home — suffered cardiac arrest and died, the suit says.

The lawsuit, filed in federal court in Newark, New Jersey, accuses Glenmark of a “systematic disregard for drug safety” and alleges the company sold pills “more suitable for an execution” than for the vulnerable patients they were supposed to help. Cormier’s pharmacy confirmed that her pills came from recalled batches, the lawsuit says. The suit is seeking class-action status.

In a court filing, Glenmark denied the allegations. The company’s attorneys listed dozens of defenses, including that the injuries claimed were the result of preexisting or unrelated medical conditions and that the product contained an adequate warning. There can be other reasons for a spike in potassium, and ProPublica was unable to independently verify key details in the suit. Cormier’s daughter referred a reporter to her attorney, Aaron Block, who declined to release Cormier’s medical records, citing the early stage of the litigation.

It’s not clear when Cormier’s pharmacy first learned the pills could be dangerous, but news of recalls can often take time to reach pharmacists — and longer to get to patients. The suit says Cormier’s pharmacy dispensed the pills on June 25. That was the day the FDA posted the recall on its website and three days before Cormier died. Medicines in the U.S. often pass through distributors. The manufacturer is responsible for notifying its distributors, who then have to notify their customers and so on down the supply chain.

News of the recall didn’t reach Cormier’s family until three weeks after her death. As her family was preparing for her memorial, a letter arrived. Cormier’s health insurance company was writing with “important drug recall information” about her potassium chloride: “Our records show that you may have recently filled a prescription for this product.” The letter made it clear that the pills may cause high potassium levels, potentially leading to cardiac arrest and death.

Glenmark knew there was a problem with its potassium chloride at least a month before Cormier died.

On May 29, a Glenmark executive wrote a letter to distributors saying a batch of potassium chloride had failed to dissolve correctly in a test, so the company was issuing a recall. The executive told the distributors that the recall was “being made with the knowledge of the Food and Drug Administration” and used red capital letters to mark the notice “URGENT.” The letter was sent via FedEx overnight. But the company and the FDA didn’t tell the public at the time.

In late June, Glenmark recalled dozens more batches, including the pills that the lawsuit says Cormier took.

On June 25, about four weeks after the Glenmark executive had written to distributors, the FDA finally alerted the public.

Glenmark and the FDA declined to say why the initial recall in May didn’t include all of the faulty pills or why they didn’t tell the public sooner. Speaking generally, Hils, the FDA spokesperson, said that the agency does not have the authority to mandate recalls of most drugs, with a limited exception for controlled substances. The agency’s role, she said, is “to oversee a company’s recall strategy, assess the adequacy of the company’s action, and classify the recall.”

Since then, Glenmark has told the FDA about reports it received of the deaths, hospitalizations and other serious health problems in patients who took the recalled potassium chloride. Companies are required to file reports to the FDA’s Adverse Event Reporting System so the agency can monitor the safety of drugs. The FDA’s online database includes only bare-bones details, so ProPublica was unable to independently verify what happened in each case. While the FDA would not comment on these complaints, the agency generally warns, “For any given report, there is no certainty that a suspected drug caused the reaction.”

A majority of the reports said the patients suffered from abnormal heart rhythms, while the second-most-common complaint was of muscle problems. Glenmark’s public alert said that the recalled pills could cause irregular heartbeats and severe muscle weakness.

Glenmark’s top executives have told financial analysts on earnings calls that the company has invested in improvements to its factories.

The company’s troubles with U.S. regulators are so well known to investors that its compliance officer notified the National Stock Exchange of India in September that FDA inspectors had found no problems at one of its other factories in India. As the news spread, Glenmark’s stock jumped 9%.

Filed under: General Problems