By Megan Rose and Debbie Cenziper
The dispatches from one of India’s most troubled generic drug makers were contrite, filled with far-reaching promises to clean up its factory, stop contamination and send safe medication to Americans counting on the company’s drugs.
“We have started addressing FDA concerns very aggressively and comprehensively,” an executive from Sun Pharma wrote to the U.S. Food and Drug Administration in 2015.
“Sun is ensuring the presence of a strong, independent quality unit,” the company repeatedly pledged.
An FDA inspection in 2014 had turned up dangerous violations at Sun’s factory in the Indian city of Halol, and the details were grim: Managers weren’t following basic rules to prevent the contamination of injectable drugs. They had failed to determine whether “unknown impurities” found in medication were toxic. The factory itself was in disrepair. The ceiling leaked and investigators observed dripping water, another dangerous contamination risk, collecting in buckets in a sterile manufacturing area.
Sun vowed bold reform at the factory, its flagship for the U.S. market. In a series of letters to the FDA after the inspection, executives described a long list of “enhancements” in facilities, in staffing, in quality standards, in training.
But for eight years, as inspectors returned and discovered again and again that Sun’s efforts were grossly inadequate, the FDA did little to warn the public or stop the drugs from coming to the United States.
The trove of Sun correspondence obtained by ProPublica provides a rare glimpse into private discussions between the global drugmaker and the U.S. regulator singularly responsible for protecting consumers from unsafe medication. The documents show how often the FDA tolerated Sun’s broken promises and substandard manufacturing, allowing an uninterrupted flow of generics to an American public clamoring for cheaper medication.
As Sun’s fixes fell short, the agency in 2015 even declared the factory’s products “adulterated” which, according to federal law, means they were produced in a way that could have compromised their strength, quality and purity.
Not until the final weeks of 2022 would the agency bar the factory from shipping its drugs to the U.S. Even then, regulators immediately excluded more than a dozen medications from the ban. The exemptions allowed Sun to continue sending those drugs — with few restrictions and no regular testing by the FDA.
In June, 11 years after that first alarming inspection, the agency went back to the factory and chronicled practically identical deficiencies. Equipment was still dirty. Injectable medications still had impurities. One worker wasn’t wearing clean gloves.
The failings convinced the FDA to keep the import ban in place, but the agency continued to allow Sun to send exempted drugs to the United States.
“Would you trust somebody who repeatedly lies to you?” said Dinesh Thakur, an industry whistleblower and drug-safety advocate. “I don’t know how you can justify your decision to try to give them a pass every time. … You are basically putting people at risk.”
More than 20 foreign factories banned from the U.S. market have received similar exemptions from the FDA since 2013 through a little-known practice used by the agency to prevent drug shortages. ProPublica reported in June that antibiotics, anti-seizure drugs and chemotherapy treatments were shipped from those plants even after inspectors identified critical violations in the way drugs were made. In all, more than 150 drugs or their ingredients received exemptions.
And, just like with Sun, the FDA never shared the details with the doctors prescribing the medications or the patients taking them. (ProPublica compiled a list of exempted drugs and ingredients since 2013.)
The agency did not respond to questions about the Sun factory, the decision to wait eight years to impose the ban or the exemptions that followed, saying only it could not discuss potential or ongoing compliance matters. The FDA referred further inquiries to Sun.
The FDA also did not answer directly whether it believed that drugs exempted from Sun’s Halol plant and the other factories were safe. To “help assure consumer safety,” the agency said, companies are required to subject exempted drugs to extra testing with third-party oversight before the medications are sent to the United States.
ProPublica’s review of the FDA’s own records, however, shows the potential weakness of such a system. Some of the companies were caught providing unreliable testing records to the FDA before they received exemptions. FDA inspectors have found managers at Sun’s Halol factory repeatedly disregarded the results of tests showing drugs were tainted with impurities. In 2019, inspectors also discovered that Sun employees could access computer systems without oversight and edit microbiological test results to potentially minimize troubling findings.
“All of the inspectors I know who do inspections in India were aware of the problems” at Sun, said one veteran FDA investigator who did not want to be identified because they were not authorized to speak publicly. “You just worry about the patients.”
Since the 2014 inspection, FDA records show, the agency has received thousands of reports from doctors and others noting concerns about the drugs that Sun makes at the Halol factory and at other plants. The complaints described potential contamination and other quality issues, or patients who had experienced sudden or unexplained health problems. The FDA cautions that the outcomes in the reports may have no connection to the drugs or could be unexpected side effects. Drug safety experts say there is no way to know for sure without further study.
Sun did not respond to detailed questions about its regulatory history. In an email, the company said it has upgraded the Halol facility and collaborated with manufacturing consultants and is testing to verify that drugs made there are safe and effective. Adherence to quality standards, the company said, “is a top priority for Sun, and we maintain a relentless focus on quality and compliance to ensure the uninterrupted supply of medicines to our customers and patients worldwide. We continue to work proactively with the US FDA and remain committed to achieve full resolution of any FDA regulatory issues at our facilities.”
Sun has been making that same promise for years.
Sun, one of the leading exporters of medications to the United States, began its campaign to win back the trust of the FDA shortly after three inspectors in September 2014 traveled to the Halol factory in western India and found the worrisome violations.
At the plant, the investigators zeroed in on the production of injectable medications. Delivered directly into the body, the drugs can be particularly dangerous, even lethal, when contaminated. But the factory, inspectors found, had no procedures to prevent the contamination of sterile drugs, according to the report.
One month later, Sun wrote to the FDA, saying it had brought on consultants to address quality issues, develop training programs and conduct audits of the factory.
“We take very seriously each of the issues that FDA has raised,” the company wrote. “Sun understands the concerns … and fully appreciates the need for a complete and comprehensive response and a robust compliance enhancement plan to address these matters.”
The letter was sent by two Sun vice presidents — one the head of quality, the other in charge of global manufacturing. They committed to sending a written update every other month, beginning in December that year, about changes for “long-term compliance.”
By February 2015, in its second update to the FDA, Sun touted more than 120 fixes at the factory. But based on its previous inspection, the FDA still issued a warning letter, which called the factory’s drugs “adulterated.”
“It is essential that executive management systematically improve their oversight of manufacturing quality,” the agency admonished in the December 2015 letter.
The company quickly responded, dispatching executives to FDA headquarters in Maryland to deliver personal assurances that the factory was falling in line. “We appreciated the opportunity to discuss Sun’s substantial progress,” two of the company’s quality managers wrote after the January 2016 visit. “Sun remains focused to deliver substantial improvements.”
Sun pledged to spend $218 million on facility improvements, according to one of its letters to the FDA. But inspectors in 2016 turned up more problems. Once again, Sun promised reform and detailed the steps it would take to fix violations.
This time, Sun sought to reassure the FDA about the production of a generic drug, carbidopa and levodopa, used to treat tremors and other effects of Parkinson’s disease. Some of the factory’s tablets were not dissolving properly when ingested, according to a Sun letter that year. That could have left patients with too little of the key ingredient needed to control the disease, or too much of it.
Sun told the FDA that an internal review was underway and the company would assess any other drugs with similar quality issues. Sun soon recalled 8,500 bottles of the drug in the United States.
More letters from Sun followed in 2017, some addressed directly to Carmelo Rosa, a longtime director of quality at the FDA’s Center for Drug Evaluation and Research, which oversees drug safety. The agency did not respond to a request for comment from Rosa, and Rosa did not respond to an email or LinkedIn message.
Inspectors went back to the factory in February and August 2018, unearthing more problems. In December that year, inspectors visited again — this time because Sun wanted to introduce three new injectable medications into the U.S. market. The inspectors noted that earlier problems had been corrected, records show.
But just one month later, Sun recalled 135,000 vials of vecuronium bromide, a muscle relaxer used during surgery, saying glass particles had been found and could cause life-threatening blood clots. The company at the time said it had not received any reports of harm.
Inspectors went back to the factory two more times in 2019, once in June and again in December, and found more problems with the way injectable medications were made. The December inspection was so alarming that the FDA held an urgent teleconference with the company, according to records obtained by ProPublica, which last year sued the agency in federal court to gain access to the information.
Despite the concerns, another FDA group — tasked with preventing drug shortages — reached out to Sun after the inspection to make sure that the factory would continue to produce the cancer drug doxorubicin. Sun promised it would.
The records show that for a series of important discussions with Sun, the FDA excluded the team that oversaw the inspections at the factory and were best informed about what was happening there.
“It would have been very helpful” to have the inspection division “plugged in from the beginning,” one team member emailed colleagues and his management in the months after the inspection.
Around that time, the company temporarily shut down the factory’s sterile manufacturing line, according to an email that Sun sent to Rosa. The plant was making 16 injectable drugs for the U.S. market.
Early the next year, Sun assured Rosa that it had done extensive reviews and submitted a strategy to again ship injectables to the United States.
That included testosterone, which is used to treat everything from low libido to bone health. But when patients got their bottles, some took to social media to describe the appearance of unusual crystals.
“They won’t go away, is it okay to use?” one person posted on Reddit in 2021. “I need to do my shot today.”
Crystals in testosterone vials are not unusual, and Sun and other manufacturers include instructions on the label to get rid of them by warming the product. FDA inspectors, however, went back to the factory in Halol in 2022 and found that Sun had received hundreds of complaints about the crystals, including two that noted it took more than five hours to dissolve them when it should normally only take minutes.
Sun said it had investigated the concerns and concluded the testosterone was acceptable. But the company couldn’t provide documentation that showed workers were properly trained or qualified to run the tests and ultimately could not produce data confirming the crystals properly dissolved, the FDA found.
Inspectors issued another damning report. Six months later, in December 2022, the FDA assessed its toughest penalty: banning the Halol factory from shipping drugs to the United States. The move came eight years after Sun started pledging reforms. And the FDA then undercut its sanction by quickly exempting more than a dozen drugs from the ban.
In the latest inspection in June of this year, inspectors found the factory failed to investigate bacteria found in test vials, disinfect manufacturing areas and equipment or properly handle vials and stoppers meant for sterile medications, according to the report.
Though the FDA published on its website warning letters sent to the factory, it has never alerted the public about the problems in a comprehensive way or provided a list of the drugs made there. The names of Halol’s products are blacked out on inspection reports so consumers can’t check their medications and make informed decisions about whether to take them.
“Your family members are taking these drugs, and are they safe? Well, maybe, well maybe not,” said former FDA inspector Patrick Stone, who now advises pharmaceutical companies. “The FDA turns a blind eye. If your market [share] is big enough, then you get leeway.”
In 2023, Sun’s billionaire founder said the introduction of new products and gains in market share made the company well positioned to “exploit the growth opportunity in the U.S. market.”
Despite the long list of critical inspection reports, five drugs made at Sun’s Halol factory are still allowed into the U.S. 2 1/2 years after the FDA issued the import ban. The exempted medications are vecuronium bromide and doxorubicin, as well as: divalproex delayed release tablets, which are used to treat seizures and migraines; leuprolide injections, which are used by people with prostate cancer, endometriosis and other conditions; and temozolomide capsules, which treat brain cancer.
Current and former FDA inspectors and others said the agency should have acted faster, responding to the problems its inspectors uncovered rather than buying into Sun’s assurances.
One senior FDA employee familiar with the inspections said they feared the company didn’t have the know-how to make safe drugs.
“Is it that they’re trying to hide stuff? Is it that they’re trying to protect? Or is it that they have no clue how to be doing these things?” said the staffer, who declined to be identified because they were not authorized to speak publicly. “Why would you get on the phone with FDA and brag that you have all these systems in place and you didn’t?”
The adverse event reports about the company’s drugs submitted to the FDA over the years describe choking, vomiting and blistering, or say that the drugs potentially caused or contributed to “toxicity,” cardiac arrest and renal failure, among other reactions, government records show. Hundreds of the complaints describe medications with possible contaminants, drugs that didn’t dissolve properly and other quality and safety concerns.
Sun’s testosterone alone was the subject of more than 500 reports, including ones describing swelling, increased heart rate, burning sensations or pain, among other symptoms, records show.
Today, years after investigators first identified problems, the senior FDA employee said the threat of harm lingers.
“The people on the other end have faith that the products they are taking are safe and effective,” said the staffer. “I think of the faces. I think of my parents. … I think of the consumers who are basically taking these drugs on blind faith.” [ProPublica/VP]