Joe DeMayo always knew that his healthy years could end suddenly. But as a father of a toddler, he wanted to spend more time.
When he was 33, his wife donated her kidneys to him. This is a milestone that changed the course of Demayo's life. The itchy skin brought about by relentless fatigue, bleeding noses, and inadequately functional kidneys disappeared, and he felt enough to leave his home in Philadelphia for a new beginning in the Northern California hills.
On a long afternoon, DeMayo hiked the mountains with his wife and black and white Mutto, Faust. When his son was born, he imagined himself coaching a baseball game in which he was dressed in Phillies gear.
However, his donated kidneys began to fail much earlier than expected in early 2023. This decline was a surprise to DeMayo, who was faithfully taking his medication, including the essential tacrolimus. Immunosuppressive drugs It helps to stop organ rejection.
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Courtesy of Joe Demayo
DeMayo didn't know that the capsules he swallowed twice a day could have made him vulnerable exactly 12 hours apart, or that one of the world's most frightening drug regulators could have failed to protect him.
As he got weaker, his kidneys were unable to cleanse the body of excess liquid and waste, and Food and Drug Administration investigators headed towards western India to inspect the factory that produced demayo tacrolimus and other generic drugs aimed at American consumers.
It was the eighth time the FDA has been there since at least 2015, and each of those visits revealed issues with how to make the medicine, government records show.
During Spring 2023 inspections, investigators discovered that Intas Pharmaceuticals Factory had, among other things. Manipulated drug test records Hides the presence of particulate matter that may contain glass, fiber, or other contaminants in company drugs.
Demayo continued taking tacrolimus capsules because he was unaware of the test. He fought fatigue and struggled to hold onto his job behind the deli counter.
“Daddy needs a new kidney,” he recalls telling his then-5-year-old son.
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George Aetage, Special Propublica
That November, the FDA banned the drug from exporting to the Intas factory to the US. However, under the long-standing practices revealed by Propublica, the agency excluded certain drugs from factory-wide bans, including tacrolimus, allowing the drug to continue flowing to the US.
In a statement to ProPublica, Intas, a US subsidiary, said the company cannot comment on individual patient cases, but that tacrolimus is safe and effective. The company said it had quickly responded to FDA inspection results, launched a quality-focused program, investing millions of dollars in upgrades and new hires. Intas also said that some exempt drugs will not be shipped to the US, but will not provide details.
“Intas is on track to complete restoration of all manufacturing sites,” the company said.
A Propublica investigation found that the FDA has allowed more than 150 drugs or their ingredients from factories that have been banned over the past decades to ostensibly prevent drug shortages.
The agency did not routinely test or actively search for signs of sudden or unexplained reactions between patients. And the exemption was largely hidden from the Congress and the people, including patients like Demayo, who relied on his medicines to keep him alive.
DeMayo filled another prescription of tacrolimus a few days before the FDA was exempt from the INTAS import ban and continued taking the capsules until just before his second transplant surgery at Temple University Hospital in January 2024.
“I'm trying to do the right thing, I'm trying to take all the medication,” said Demayo, 45, who took Intas Tacrolimus for two years. “If I'm doing it all, why don't someone do their due diligence?”
In a statement, the FDA said drugmakers who have received a pass from the import ban should carry out additional safety and quality testing and evaluate the results before hiring third party experts to deliver to the US. Current and former FDA officials said these measures were flawed. Many companies have previously been cited for testing protocols that are ineffective or prone to fraud.
Now recovered from his second transplant surgery, DeMayo has given Propobrica two bottles of unused tacrolimus capsules. Propublica tested with Valisure Independent Certified Lab In Connecticut.
In the first test, Valisure scientists discovered that some of the tablets in Demayo contained an appropriate amount of key ingredients, while others contained less than the minimum levels set by US regulations. Pharmacists, doctors and other experts said Unprocessed It can make patients vulnerable to organ rejection.
Courage discovered no substantial contamination in Demayo's medicine.
However, scientists have discovered another potential problem. The capsules dissolved quickly – up to 3 times faster than the name brand. Fast dissolution can cause the drug to be introduced too quickly, experts said, which can cause trembling, headaches and kidney failure.
Propublica did not test tacrolimus made by other manufacturers. In that statement, Intas said the findings were “unrelated.” [FDA’s] Testing and the FDA determined that the drug was comparable to the brand version when it was first approved in the US market.
Valisure previously tested tacrolimus from the Department of Defense Intas. Safety and Quality Testing with more than 30 drugs commonly used by service members in the US and their families. These tests also showed that the capsules had melted too much.
“This is an incredible signal of other quality issues that could affect patient care,” said a retired Army colonel who has launched the Department of Defense efforts and is supporting the project.
The FDA has carried out its own implementation. Intas' tacrolimus study In recent years, similar results have been reported on its website. The agency noted there is no obvious risk of organ rejection, but said generics intas can produce toxins in the body, causing kidney damage. The FDA said the capsules may not provide the same therapeutic effect as the branded version.
The survey results have been published In September 2023, weeks later, the agency excused the drug from the Intas import ban and allowed the company to continue shipping Tacrolimus to the US.
Janet Woodcock, who headed the FDA's Center for Drug Evaluation and Research for many years, said in an interview that the test results were concerning and that the agency should “try to sort it out” immediately.
“This was clearly a quality issue,” she said.
Woodcock did not say why the FDA exempts the drug from the import ban imposed on the Intas factory. Woodcock approved the exemption for years, but she left the centre and served as the FDA's primary vice-committee when exemptions for tacrolimus and other INTAS drugs were made.
Demayo never knows whether the drug contributed to the loss of the donated kidneys. Organ rejection, which can occur immediately or over many years, is the most common Common causes Joseph Vassarotti, chief medical officer at the National Kidney Foundation, said that kidney failure in transplant patients could also fail for other reasons.
In Demayo's case, he was hospitalized with gastric virus and dehydration the same year that his kidney function began to decline. Still, he questioned the drugs that are supposed to protect him and worried that other transplant patients who have taken tacrolimus could be at risk.
A year and a half after the FDA banned the factories from transporting drugs to the US, tacrolimus is still being ruled out. The company's customer service agent said Intas recently stopped distributing drugs, but the company did not respond to a request for comment.
“People who oversee pills have failed, and people who make pills have failed,” DeMayo said. “Why did it get so bad?”
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1st and 3rd photos: Hannah Yoon from Propublica. Second photo: George Aetage, special Propublica.
Lucas Waldron provided graphics and development.
