by Megan Rose and Debbie Cenziper
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Joe DeMayo was always aware that a transplanted kidney’s lifespan, which was roughly the length of a tiny fist, could instantly end his healthy years. But as the father of a child, he had hoped to have more day.
His family donated her liver to him when he was 33, a moment that altered DeMayo’s life forever. He felt good enough to keep his Philadelphia home for a new beginning in the highlands of northern California after enduring constant exhaustion, nose bleeds, and itchy body brought on by his own badly functioning organs.
Over long days, DeMayo may hike in the highlands with his family and their black-and-white dog, Fausto. When his son was born, he had imagined himself playing sports games while wearing Phillies products.
However, his donated liver started to fail in the early 2023 period, much sooner than expected. The drop came as a shock to DeMayo, who had been diligently taking his medications, including tacrolimus, an important suppression substance that helps fend off organ rejection.
Joe DeMayo, his woman, and child at Christmas in 2022. He may need a minute liver transplant about a year later. ( Courtesy of Joe DeMayo )
DeMayo wasn’t aware at the time that the capsules he took half a day, exactly 12 hours off, might have made him vulnerable, or that one of the world’s toughest drug regulators might not have been able to protect him.
Investigators from the Food and Drug Administration traveled to northern India to check the factory where DeMayo made tacrolimus and another general drugs for American consumers as he grew weaker and his liver failed to purge his body of excess liquid and waste.
It was at least the eighth time since 2015 that the FDA had been there, and each of those visits had uncovered problems in the way the drugs were made, government records show.
Investigators found that the Intas Pharmaceuticals factory had, among other things, manipulated drug-testing records to conceal the presence of particulate matter in the company’s products during the inspection in the spring of 2023. This could have included glass, fiber, or other contaminants.
DeMayo continued taking his tacrolimus capsules despite being unaware of the inspection. He fought exhaustion and struggled to hold onto his job behind a deli counter.
He recalled telling his 5-year-old son at the time,” Daddy needs a new kidney.”
DeMayo’s tacrolimus ( George Etheredge, special to ProPublica ) is available.
That November, the FDA barred the Intas factory from exporting drugs to the United States. However, the organization exempted some medications from the factory-wide ban, including tacrolimus, allowing the drugs to continue to flow into the U.S. in response to a long-standing practice that ProPublica discovered.
Intas, whose U.S. subsidiary is Accord Healthcare, stated in a statement to ProPublica that the company was unable to comment on individual patient cases but that tacrolimus is safe and effective. The company said it immediately responded to the FDA’s inspection findings, launching a program focused on quality and investing millions of dollars in upgrades and new hires. Intas added that some exempted drugs were never shipped to the US, but they would not provide specifics.
The company stated that Intas is well on its way to complete remediation of all manufacturing sites.
ProPublica’s investigation found the FDA has allowed more than 150 drugs or their ingredients from banned factories into the country over the past dozen years, ostensibly to prevent drug shortages.
The organization did not regularly check the dosage of the medications or actively look for symptoms of sudden or unusual reactions in patients. And patients like DeMayo, who relyed on his medication to keep him alive, were largely kept secret from Congress and the general public.
DeMayo filled another prescription for tacrolimus only days before the FDA exempted it from the Intas import ban and continued taking the capsules until just before his second transplant surgery at Temple University Hospital in January 2024.
DeMayo, 45, who took Intas tacrolimus for two years, said,” I’m trying to do the right thing and take all my medicine.” If I’m doing all of that, shouldn’t someone else be doing their due diligence?
In a statement, the FDA said drugmakers that receive a pass from import bans are required to conduct additional safety and quality testing and hire third-party experts to assess the results before shipping medication to the United States. These measures, according to current and former FDA officials, are flawed. Numerous businesses have previously been cited for analyzing ineffective or fraud-prone protocols.
DeMayo, now recovered from his second transplant surgery, gave ProPublica two bottles of his unused Intas tacrolimus capsules. At Valisure, a private, reputable lab in Connecticut, ProPublica tested them.
The Method of Testing
I. DeMayo’s medication was subjected to three separate tests at preparation company Valisure. For two of the analyses, technicians poured the samples onto a scale so precise that it shields the samples from the movement of air. The material was then put into a solution for testing.
II. Dosage AssessmentFor the first assessment, technicians used a machine to separate, identify, and quantify the compounds in the solution.
The liquid was poured into tiny vials and then assessed for physical and chemical properties. The analysis revealed how much of the main ingredient in the medication was present and whether the dosage levels were within the prescribed range.
III. Testing for ContaminantsValisure also tested the drug for the presence of toxic elements, including lead, arsenic and mercury. The liquid was transferred to a machine that uses plasma that is 18, 000 degrees, which is hotter than the sun’s surface, to break down chemicals into atoms.
IV. Testing for DissolutionIn the third assessment, a technician prepared a liquid that simulates stomach acid.
The technician then placed the pills into tiny metal cages and threw them into the liquid.
The testing device evaluated whether the medication disintegrated quickly and whether the capsules delivered the correct dosage of medication at the right time.
( Photography by George Etheredge, special to ProPublica )
In their first test, the researchers from Valisure discovered that some DeMayo’s pills had enough of the key ingredient, while others had less than the required amount per U.S. regulation. According to doctors, pharmacists, and other experts, underdosing can make patients more susceptible to organ rejection.
Valisure did not find any substantive contamination in DeMayo’s medication.
The researchers, however, discovered a different possible issue. Up to three times as quickly as the name brand, the capsules dissolved. Rapid dissolution can introduce too much of the drug too quickly, experts said, potentially causing tremors, headaches and kidney failure.
Note: The Weibull model was used to model the data by Valisure. The data for 1 mg capsules is modeled in the chart. ( Lucas Waldron/ProPublica )
No other manufacturers ‘ tacrolimus was tested by ProPublica. In a statement, Intas claimed that the findings are “unrelated to the]FDA’s ] inspections” and that the FDA had determined that the drug was the same as the brand-name version when it was first approved for the U.S. market.
Valisure previously tested Intas ‘ tacrolimus for the Department of Defense, which is conducting safety and quality testing on more than three dozen drugs commonly used by U. S. service members and their families. Those tests, too, revealed that the capsules dissolved too quickly.
This is an alarming sign of other quality issues that might be having an impact on patient care, according to retired Army Col. Vic Suarez, who helped spearhead the effort of the Defense Department and is working on the project.
The FDA conducted its own studies of Intas ‘ tacrolimus in recent years and reported a similar result on its website. The organization noted that there was no obvious risk of organ rejection, but claimed that the Intas generic could release toxins that could harm kidneys. According to the FDA, the capsules may not have the same therapeutic effect as the brand-name version.
The findings were made public in September 2023. The company continued to ship tacrolimus to the United States thanks to the agency’s continued excuses for the drug’s importation from the Intas.
Janet Woodcock, who has for years been in charge of the FDA’s Center for Drug Evaluation and Research, stated in an interview that the agency should” try them out” right away.
” This obviously was a quality problem”, she said.
Woodcock did not explain why the FDA exempted the drug from the import restriction placed on the Intas factory. Although Woodcock had been approuving exemptions for years, she had left the organization and was working as the agency’s principal deputy commissioner when the exceptions for tacrolimus and other Intas drugs were issued.
DeMayo said he’ll never know whether the medication contributed to the loss of his donated kidney. Organ rejection, which can occur quickly or over years, is one of the most frequent causes of kidney failure in transplant patients, according to Joseph Vassalotti, chief medical officer at the National Kidney Foundation.
In DeMayo’s case, his kidney function started to decline the same year his stomach virus and dehydration caused him to be hospitalized. Still, he questions the drug that was supposed to protect him and worries that other transplant patients who have taken Intas tacrolimus could be at risk.
Taclofimus is still prohibited one and a half years after the FDA forbade the factory from sending drugs to the US. According to a customer service representative for the business, Intas recently stopped dispensing the drug, but the company did not respond to a request for comment.
” The people who oversee the pills are failing and the people who are making the pills are failing”, DeMayo said. How did it get to this point?
DeMayo visited Temple University Hospital for a follow-up appointment in January, one year after receiving his second kidney. ( First and third photos: Hannah Yoon for ProPublica. Second image: George Etheredge, a ProPublica special.
Lucas Waldron contributed to the creation of the graphics.
Originally sourced via trusted media partner. https://www.propublica.org/article/fda-tacrolimus-kidney-transplant-patient
