Threat in Your Medicine Cabinet: The FDA’s Gamble on America’s Drugs/ ProPublica

I have removed the photos as ProPublica requested--to see them go to the ProPubica site. This is the FDA the administration is contending with, as it hides its inner workings

https://www.propublica.org/article/fda-drug-loophole-sun-pharma

Reporting Highlights

• Risky Medications: The FDA has given more than 20 foreign factories a special pass to continue sending drugs to the U.S. even though they were made at plants that the agency had banned.

• Troubled Factories: The medications came mostly from plants in India where inspectors found contaminated drugs, filthy labs and falsified records.

• FDA Secrecy: The agency did not proactively inform the public when drugs were exempted from import bans, and it did not routinely test the medications to ensure they were safe.

On a sweltering morning in western India in 2022, three U.S. inspectors showed up unannounced at a massive pharmaceutical plant surrounded by barricades and barbed wire and demanded to be let inside.

For two weeks, they scrutinized humming production lines and laboratories spread across the dense industrial campus, peering over the shoulders of workers at the tablet presses, mixers and filling machines that produce dozens of generic drugs for Americans.

Much of the factory was supposed to be as sterile as an operating room. But the inspectors discovered what appeared to be metal shavings on drugmaking equipment, and records that showed vials of medication that were “blackish” from contamination had been sent to the United States. Quality testing in some cases had been put off for more than six months, according to their report, and raw materials tainted with unknown “extraneous matter” were used anyway, mixed into batches of drugs.

Sun Pharma’s transgressions were so egregious that the Food and Drug Administration imposed one of the government’s harshest penalties: banning the factory from exporting drugs to the United States.

But the agency, worried about medication shortages, immediately undercut its mission to ensure the safety of America’s drug supply.

A secretive group inside the FDA gave the global manufacturer a special pass to continue shipping more than a dozen drugs to the United States even though they were made at the same substandard factory that the agency had officially sanctioned. Pills and injectable medications that otherwise would have been banned went to unsuspecting patients across the country, including those with cancer and epilepsy.

The FDA didn’t routinely test the medications for quality problems or use its vast repository of drug-related complaints to proactively track whether they were harming the people who relied on them.

And the agency kept the exemptions largely hidden from the public and from Congress. Even others inside the FDA were unaware of the details.

In the hands of consumers, according to the FDA’s longtime head of drug safety, the information would have caused “some kind of frenzy.”

“We felt we didn’t have to make it a public thing,” said Janet Woodcock, who spent nearly four decades at the agency.

The exemptions for Sun weren’t a one-time concession. A ProPublica investigation found that over a dozen years, the same small cadre at the FDA granted similar exemptions to more than 20 other factories that had violated critical standards in drugmaking, nearly all in India. All told, the group allowed into the United States at least 150 medications or their ingredients from factories with mold, foul water, dirty labs or fraudulent testing protocols.

Some of the drugs were recalled — just before or just after they were exempted — because of contaminants or other defects that could cause health problems, government records show. And a ProPublica analysis identified more than 600 complaints in the FDA’s files about exempted drugs at three of those factories alone, each flagging concerns in the months or years after they were excluded from import bans in 2022 and 2023.

The “adverse event” reports about drugs from the Sun plant and two others run by Indian drugmaker Intas Pharmaceuticals described medication with an abnormal taste, odor or residue or patients who had experienced sudden or unexplained health problems.

The reports cite about 70 hospitalizations and nine deaths. And those numbers are conservative. ProPublica limited its count to reports that linked problems to a single drug. However, the total number of complaints to the FDA that mention exempted drugs is in the thousands.

“Abdominal pain … stomach was acting very crazy,” one report said about a woman using a seizure drug from Sun Pharma. The FDA received the complaint in 2023, nine months after it excluded the medication from the import ban.

“Feeling really hot, breaking out with hives, hard to breathe, had confusion, glucose level was high, heart rate went up and head, arms and hands got numb,” noted another report about a patient taking a sedative from Intas. The complaint was sent to the FDA in June 2023, the same month the agency exempted the medication.

The outcomes described in the complaints may have no connection to the drug or could be unexpected side effects. In some cases, the FDA received complaints about the same drugs made by other manufacturers.

Still, the seriousness of the reports involving exempted drugs did not galvanize the agency to investigate, leaving the public and the government with no way of knowing whether people were being harmed and, if so, how many.

Those unknowns have done little to slow the exemptions. In 2022, FDA inspectors described a “cascade of failure” at one of the Intas plants, finding workers had destroyed testing records, in one case pouring acid on some that had been stuffed in a trash bag. At the second Intas factory, inspectors said in their report that records were “routinely manipulated” to cover up the presence of particulate matter — which could include glass, fiber or other contaminants — in the company’s drugs.

The FDA barred both plants in 2023 from shipping drugs to the U.S. Then the agency simultaneously granted more than 50 exemptions to those banned factories — the broadest use of exclusions in ProPublica’s analysis.

Intas, whose U.S. subsidiary is Accord Healthcare, said in a statement that the company has invested millions of dollars in upgrades and new hires and launched a companywide program focused on quality. Exempted drugs were sent to the United States in a “phased manner,” the company said, with third-party oversight and safety testing. Intas also said that some exempted drugs were never shipped to the United States because the FDA found other suppliers. The company would not provide details.

“Intas is well on its way towards full remediation of all manufacturing sites,” the company said.

Sun did not respond to multiple requests for comment. When the FDA imposed the ban, the company said it would “undertake all necessary steps to resolve these issues and to ensure that the regulator is completely satisfied with the company’s remedial action. Sun Pharma remains committed to being … compliant and in supplying high-quality products to its customers and patients globally.”

Both companies’ factories are still under import bans.

“We’re supposed to have the best medicine in the world,” said Joe DeMayo, a kidney transplant patient in Philadelphia who took an immunosuppression medication made by Intas until December 2023, unaware that a month earlier the FDA had excused the drug from an import ban. “Why are we buying from people who aren’t making it right?”

Game of Chance

How the United States wound up here — playing a game of chance with risky drugs made thousands of miles away — is the story of an agency that has relentlessly pressed to keep the supply of low-cost generics flowing even as its own inspectors warned that some of those drugs posed a potentially lethal threat to the American public.

The vast majority of the prescriptions filled in the country are for generic drugs, from penicillin to blood thinners to emergency contraception, and many of those come from overseas, including India and China. For years, the FDA has vouched for the quality of generics, assuring the public in press releases, speeches and social media campaigns that they are just as safe and effective as brand-name drugs.

That guarantee came under serious question in 2019 when journalist Katherine Eban published a breakthrough book, “Bottle of Lies,” that exposed rampant fraud and manufacturing violations in Indian factories and the FDA’s reluctance to aggressively investigate.

ProPublica identified another alarming level of entrenched failure: Even when the agency did investigate and single out factories that were among the worst in India, it still gave them access to American consumers. All the while, patients took their medicine without question, trusting an agency that has long been considered the gold standard in drug regulation.

While specialized business publications have sometimes reported on exemptions when they happen, they’ve offered little context and few specifics.

The FDA in many ways put itself in this untenable position, forced to decide between not having enough drugs or accepting potentially dangerous ones, interviews and government records show.

For years, the agency gave companies with a history of manufacturing breakdowns approval to produce an increasingly larger share of generic drugs, allowing them to become a dominant force in American medicine with the power to disrupt lives if production lines were shuttered.

“It’s our own fault,” said former FDA inspector Peter Baker, who reported a litany of failures during inspections in India and China from 2012 to 2018. “We allowed all these players into the market who never should have been there in the first place. They grew to be monsters and now we can’t go back.”

The decisions to weaken penalties and allow banned factories to continue sending drugs to the United States were approved by Woodcock, one of the agency’s most powerful administrators. For more than two decades, she led the Center for Drug Evaluation and Research, the arm of the FDA that serves as the country’s gatekeeper for new and generic drugs.

In a series of interviews with ProPublica, Woodcock said she supported the use of exemptions “as a practical approach.”

“We had to kind of deal with the hand we were dealt,” she said.

Woodcock said she didn’t see a need to inform the public because the agency believed the drugs were safe. She said she mentioned the practice periodically in closed-door meetings with congressional staffers, but she did not provide specifics about those conversations.

After Woodcock left her post in 2020 to help lead the agency’s response to the COVID-19 pandemic, the exemptions — including those for Sun and Intas — continued under her successor, Patrizia Cavazzoni. Cavazzoni, who left the agency earlier this year and rejoined Pfizer, declined to comment.

Former FDA Commissioner Robert Califf, who led the agency when Sun and Intas received exemptions, told ProPublica that tough calls had to be made and the practice did not worry him.

The FDA did not respond to questions about who made those decisions or how the drugs were evaluated, and it declined requests for interviews with officials who currently oversee drug regulation. In an email, the agency said the exemptions are “thoroughly evaluated through a multi-disciplinary approach.”

Years after the FDA started granting exemptions, some current and former officials say they wrestle with a lingering fear that bad drugs are circulating in the United States.

“It’s not even a hypothetical,” said one senior FDA employee familiar with the exemptions, who, like others, spoke on the condition of anonymity because they were not authorized to speak publicly. “It’s not a question of if — it’s a question of how much.”

“It Was Rotten Eggs”

Although the FDA has been giving companies a way around import bans since at least 2013, the internal process was so secretive that many current and former FDA officials said they have no idea how many exemptions have been granted or for what drugs. In an email, the agency said it did not maintain a comprehensive list.

Even two high-level FDA staff members who worked on drug shortage challenges for the agency said in interviews they had never heard of the exemptions.

Congress required the FDA in 2012 to provide specific information every year about how and when the agency relaxed its rules for errant drugmakers to prevent shortages. But the FDA did not mention exemptions to import bans until 2024 — and only then in a single footnote of its 25-page report to Congress.

ProPublica uncovered the frequent use of exemptions by searching for the “import alert” list published on the FDA’s website that names factories banned from the U.S. marketplace. Because the agency publishes only a current list and doesn’t make the old ones public, the news organization used internet archives and FDA documents maintained by the data analytics company Redica Systems, ultimately compiling import alerts dating back more than a decade. The lists identify the drugs exempted from bans but provide few other details.

ProPublica reviewed scores of inspection reports and corporate documents for overseas factories and interviewed more than 200 people, including current and former officials of the FDA, to understand the little-known practice and the ongoing threat posed by the agency’s decisions.

The investigation revealed not only how many drugs received exemptions from import bans, but also how long the FDA allowed those exemptions to stay in place — in some cases for years.

The agency has removed exemptions when there is no longer a shortage concern. In those cases, the drugs are then banned along with the others at the factory. Both Sun and Intas have had drugs that lost their exemptions.

Two and a half years after the Sun factory was banned, five drugs are still exempted. Intas, whose factories were banned in 2023, currently has 24 drugs on the list. The bans themselves are removed only after companies fix the problems.

Earlier this month, the FDA went back to the Sun Pharma factory for a surprise inspection and found ongoing problems, according to a Sun filing with the Indian stock exchange and Indian media reports. The concerns focused on the way sterile drugs were made, including some of the exempted drugs still being sent to the United States, according to a person familiar with the situation who did not want to be named because they were not authorized to speak publicly.

The FDA said it put protections in place for exempted drugs: Manufacturers are required to conduct additional quality checks before they are sent to the United States. That has included extra drug-safety testing, in some cases at an independent lab, and bringing on third-party consultants to verify the results.

The agency did not provide ProPublica with the names of the third-party consultants hired by Sun and Intas. Intas declined to name its consultants.

“The odds of these drugs actually not being safe or effective is tiny because of the safeguards,” said one former FDA official involved in the exemptions who declined to be named because he still works in the industry and fears professional retribution. “Even though the facility sucks, it’s getting tested more often and it’s having independent eyes on it.”

But current and former FDA inspectors said those safety measures require trusting the vigilance of companies that were banned, at least in part, for providing unreliable or deceptive test results to the government or failing to investigate reports about drugs with contaminants or other quality concerns.

The FDA could have done its own routine testing of the exempted drugs but chose not to. The agency said in an email that it tests the drugs using a “risk-based approach” but would not provide ProPublica with any information about which drugs have been tested and what the results were.

Woodcock said testing was expensive and budgets were tight. She acknowledged that regularly assessing the exempted drugs for quality or safety concerns “would have enhanced our confidence … and made everyone more comfortable.”

The European Union, by contrast, requires drugs made in India and China to be checked for quality on EU soil. And the U.S. Department of Defense is conducting its own testing of more than three dozen generic medications and has already identified potency and other quality issues.

“If you don’t know about the quality of the product, why are you letting it in?” said Murray Lumpkin, the FDA’s former deputy commissioner for international programs, who left the agency in 2014 before most of the exemptions were granted.

Beyond the lack of testing, the FDA didn’t actively look for patterns of harm among the exempted drugs in its adverse event database, Woodcock and others said.

ProPublica’s analysis of that data found thousands of reports both before and after the factories were given a pass to sidestep import bans. The reports described unexpected cases of cardiac arrest, blurred vision, choking, vertigo and kidney injuries, among other issues — and in some instances identified specific concerns about how the drugs were made.

One person who took Intas’ clonazepam, a sedative and epilepsy drug, reported getting “brain zaps” and bright blue teeth from the coating of dye on the drug. The FDA received the complaint the same month the agency exempted the drug from the import ban.

Even before the FDA exempted Intas’ antidepressant bupropion, consumers reported that it made them sick, wasn’t always effective and had an abnormal odor, which pharmacists and others say can happen when an inactive ingredient breaks down.

“It was rotten eggs,” Nari Miller, a geologist in California who took the pills in 2022 and had severe stomach pain, told ProPublica. “I opened it and smelled it when I got home and it was awful.”

Intas said it could not respond to specific complaints and that all drugs have side effects. “Intas and Accord pay attention to each and every adverse event report,” the company said, adding, “Accord and Intas are committed to continuing to bring safe and effective medicines to patients.”

In its statement, the FDA said the database is monitored weekly for new reports in general. Woodcock, however, acknowledged the reports about exempted drugs, ideally, “would be under much more scrutiny.”

Too Big to Fail

Decisions made by the FDA decades ago gave rise to the use of exemptions and the risks that now confront the American public.

When new brand-name drugs come to market, they are protected by patents and exclusive sales rights that make them generally expensive. When patents expire, generic drug companies rush in to make their own versions, which are supposed to be equivalent to the brand. Generics are often far cheaper, and insurance companies typically insist that patients use them.

In the 2000s, as the cost of brand-name drugs soared, the FDA began to approve large numbers of generics. The agency, however, gave hundreds of those approvals to foreign manufacturers that had been in trouble before, companies well known to the inspectors working to stamp out safety and quality breakdowns at overseas factories, ProPublica found.

The FDA granted Sun Pharma alone more than 250 approvals for generic drugs since the late 2000s, when the company started amassing violations, records show. The agency’s decisions helped to transform the company from a local provider in India to one of the leading exporters of medications to the United States, with nearly $2 billion in annual U.S. sales.

The approvals kept coming as inspectors continued to raise concerns about manufacturing practices at the company’s factories in India, government records show.

More problems were found at a factory that Sun had acquired in Detroit, where the diabetes drug metformin was contaminated with metal scrapings. The violations were so significant that federal marshals in 2009 raided the plant and seized drugs. The company eventually shuttered the factory.

The rapid expansion of Sun and other foreign drugmakers set off new alarms among inspectors, their supervisors and advisers to Woodcock.

“In a rational system, you would have said, ‘This company is not producing properly, so let’s not approve any more of their drugs,” said William Hubbard, former FDA deputy commissioner for policy, planning and legislation. “The agency in a sense kind of let this happen.”

Ajaz Hussain, the former deputy director of an FDA office that oversaw pharmaceutical science, said that after leaving the agency and becoming a consultant, he made his concerns known in meetings with Woodcock and others.

“They can’t manufacture it. Why do you keep approving it?” Hussain recalled in an interview with ProPublica. “I said, ‘Wake up.’ … But they didn’t listen.”

Hussain in 2012 went to work for Wockhardt, one of the largest pharmaceutical companies in India, but quit eight months later after he said he told his superiors about manufacturing failures in the company’s factories.

Although FDA inspectors had reported lapses after multiple visits to Wockhardt plants between 2004 and 2012, the agency cleared the way for the company to export sedatives, antibiotics, beta blockers, painkillers and other generics to the United States, records show. Wockhardt received exemptions from import bans in 2013. The company did not respond to repeated requests for comment, but at the time, the company said it was going to quickly address the FDA’s concerns.

The FDA could have denied generic drug applications — nothing in the law prohibits the agency from saying no to companies with spotty track records. In an email, the FDA said it considers a company’s history and conducts inspections in some cases before issuing approvals.

Woodcock said the agency knew which factories were poor performers but feared being sued by companies blocked from introducing new drugs based on past behavior. Instead, she said that she tried to convince drugmakers to invest in equipment and practices that would turn out higher-quality drugs.

“We had many meetings about this, and we agonized about all these problems,” she said.

But little changed.

Shortages vs. Quality

In 2008, dozens of Americans were killed by contaminated blood thinner from China. So when Margaret Hamburg was appointed commissioner of the FDA in the aftermath of the crisis, she pressed the agency to crack down on overseas drugmakers.

Her efforts ran headlong into what would become the worst drug shortage in modern history. By 2010, cancer drugs were scarce. So were the drugs on hospital crash carts. In all, more than 200 critical medications were in short supply.

Razor-thin profit margins had limited the number of companies that were willing to make generic drugs. And the FDA’s enforcement overseas had forced some manufacturing lines to temporarily shut down, which exacerbated the problem.

Congress lambasted the FDA for the shortages and started requiring the agency to prove every year how it was combatting the problem.

At the time, the FDA had a small team focused on shortages that operated on the edges of Woodcock’s 4,000-person Center for Drug Evaluation and Research. With the pressure on, Woodcock elevated the team in 2010 to report directly to her deputy, a move that gave those staff members a commanding voice at the highest levels of the agency, several former staffers told ProPublica.

After 16 years in top leadership roles, Woodcock was formidable enough to force a culture change. Standing 5’2” in FDA conference rooms where she had often been disregarded as the lone woman, Woodcock had fought for her status — sometimes, she said, pushed nearly to tears with frustration. The board-certified internist asserted her authority by wielding data, what she called “brute force” and the soft persuasion of an occasional gift of an orchid, picked from her garden in suburban Maryland.

By 2010, Woodcock had marshalled the center into a powerhouse with great independence — in many ways, outside the reach of the political whims of the commissioners who came and went. Those who worked with her over the years said despite her approachable manner, she fiercely guarded her territory.

In the conference room next to Woodcock’s office, the drug shortage staff began to weigh in whenever the FDA’s compliance team moved to penalize wayward drugmakers because of bad inspections, according to several former FDA officials involved in the deliberations.

Sometimes the small group would decide that a factory could no longer ship drugs to the United States and would try to get other manufacturers to make more. And other times, the group determined that exemptions from import bans were the only course.

Discussions could be tense and often lasted for weeks. A former employee on the compliance team told ProPublica that they repeatedly argued to impose a total import ban on a foreign factory because they feared the drugs couldn’t be trusted. They were left feeling uncomfortable about an exemption granted anyway — for a product that they would not use themselves.

Without exemptions, Woodcock told ProPublica, the FDA might have been forced to source the drugs from a “totally unknown manufacturer, say, from China or somewhere.”

Current and former FDA officials said the concessions became a yearslong practice rather than a stopgap measure and that the protections put in place by the agency were not sufficient. They question why Woodcock and her successor didn’t do more to raise alarms with Congress or the public about the decision to rely on inadequate factories for critical drugs.

Woodcock said she thought the exemptions were a symptom of larger issues involving the drug supply that the FDA had no control over — the agency, for example, can’t force companies concerned about slim profit margins to produce generic drugs.

Two former FDA commissioners told ProPublica they knew about the practice but were not included in the decision-making.

Hamburg, who spent six years at the agency under the Obama administration, said the extent of the practice surprised her. “Had I known that it was sort of an open-ended policy, I would have been disturbed,” she said.

One of her successors, Stephen Hahn, appointed during President Donald Trump’s first term, said more people should have been involved in the decisions.

“You’re talking about a drug of questionable quality being brought into the country,” he said.

Woodcock said she did not believe she needed their input. “I didn’t think in the individual circumstances it was necessary to elevate,” she said, “because what could they do?”

“We Know What Was Found”

In 2020, the billionaire founder of Sun Pharma joined a pivotal conference call with FDA compliance and investigative staff.

Dilip Shanghvi, whose father had run a wholesale drug business in Kolkata, India, started the company in the 1980s and ultimately turned Sun Pharma into one of the largest suppliers of generic drugs in the United States. On the call, Shanghvi spoke about improvements at Sun’s enormous plant in the Indian city of Halol, according to an FDA official who attended the meeting.

Among other drugs, the plant produced at least 16 sterile injectables for the U.S. market, according to a Sun email to the FDA obtained by ProPublica. Injectables are particularly dangerous if contaminated because the medication is injected directly into the body, unlike a pill that goes through the filtering of the digestive tract.

In 2018 and 2019, inspectors had reported a series of violations at the factory, and Sun had received more than 700 complaints about what appeared to be crystals or spider webs formingin one of its injectable medications, records show.

The company also had to recall more than 135,000 vials of vecuronium bromide, a muscle relaxer used during surgery, after reports that the medication contained glass particles. Sun said the defect could cause life-threatening blood clots.

On the call with the FDA, according to the agency official, Shanghvi assured the government that the Halol plant was turning out high-quality products.

Yet, when the three investigators went back to the factory that scorching morning in 2022 for the surprise inspection, it was clear within days that the FDA would have to take swift action.

Splitting up to check different parts of the plant, the inspectors quizzed workers about cleaning procedures and looked at disassembled equipment to see if it was contaminated with residue from old drugs. At one point, they spotted water leaking near areas where sterile drugs were made, an alarming observation because water can introduce contaminants capable of causing infections or even death.

Digging through company records and test results, they found more evidence of quality problems, including how managers hadn’t properly investigated a series of complaints about foreign material, specks, spots and stains in tablets.

Several FDA employees familiar with the inspection report — 23 pages of detailed violations — said they had no idea why the agency went on to exclude so many of Sun’s drugs from the subsequent import ban.

“We know what was found,” said the FDA official who attended the meeting with Shanghvi. “How could you trust [those] drugs?”

Sun did not respond to questions about the recalls or its regulatory history with the FDA. In its 2023-24 annual report, the company said, “We have a relentless focus on 24x7 compliance to ensure continuity of supplies to our customers and patients worldwide.”

The specific findings of the FDA’s latest inspection of the Sun plant conducted this month have not yet been made public, and the company did not respond to a request for comment.

To some current and former FDA officials and other experts, plugging a supply shortage with drugs that may be contaminated or ineffective is no solution at all.

“That might be helping a shortage but might be creating a new problem,” said Lumpkin, the former deputy commissioner.

Last summer, a pair of FDA investigators arrived at another manufacturing plant in India that had a bustling production line. After more than a week at the Viatris factory, they left with a familiar list of safety and quality violations.

We Spent a Year Investigating How the FDA Let Risky Drugs Into the U.S. Market

The inspectors found that equipment wasn’t clean and managers failed to thoroughly investigate unexplained discrepancies in test results.

In a statement to ProPublica, Viatris said it immediately worked to resolve the FDA’s concerns. “Patient safety remains our primary and unwavering focus,” the company said.

Just before Christmas, the FDA banned the facility from exporting drugs.

Then the agency gave the factory a pass, and four of its drugs are still bound for the United States.