FDA So Slow to Respond to GAO Recommendations about Secret Food Additives that It’s like not Responding at all
By Noel Brinkerhoff and Steve Straehley | AllGov | April 16, 2015
In 2010, the Government Accountability Office (GAO) examined the process used by the Food and Drug Administration (FDA) for regulating food additives and came up with six ways the FDA could improve this function. Five years later, FDA officials have satisfied only one of the GAO suggestions.
“It’s really clear that we have no basis to make almost any conclusions about the safety of the current food supply,” Laura MacCleery, an attorney with the Center for Science in the Public Interest, a consumer advocacy group, told the Center for Public Integrity. “We don’t know what people are eating.”
The GAO report even stated that the FDA’s oversight process does not help ensure the safety of all new food ingredients, and it criticized companies’ ability to use new added ingredients deemed generally recognized as safe (GRAS) without informing federal food regulators.
GRAS came about as a way to exempt simple ingredients in long use, such as table salt, from FDA review after food regulations were strengthened in the 1950s. However more items are added to the list each year as manufacturers use the GRAS list as a loophole to avoid having their products evaluated by the FDA.
The recommendation (“Develop a strategy to help ensure the safety of engineered nanomaterials that companies market as GRAS substances without the agency’s knowledge”) resulted in the FDA issuing a final guidance on nanotechnology last June, according to the Center for Public Integrity.
A second recommendation to develop a strategy to finalize a 1997 proposed rule that defines how companies can voluntarily submit safety determinations to the FDA for a cursory review will be completed by August 2016, according to the Center for Public Integrity.
The GAO’s four other recommendations were:
-Develop a strategy to require any company that conducts a GRAS determination to provide FDA with basic information, including the ingredient’s identity and intended uses, and post the information on the agency’s website.
-Develop a strategy to minimize the potential for conflicts of interest in companies’ GRAS determinations.
-Develop a strategy to monitor the appropriateness of companies’ GRAS determinations through random audits or some other means.
-Develop a strategy to conduct reconsiderations of the safety of GRAS substances in a more systematic manner including responding to citizen petitions in a timely manner.
To Learn More:
Why the FDA Doesn’t Really Know What’s in Your Food (by Erin Quinn and Chris Young, Center for Public Integrity)
Loopholes and Weak Enforcement Lead to Unapproved Chemicals Added to Foods (by Noel Brinkerhoff and Danny Biederman, AllGov )
35% of Food Additives Deemed Harmless were Evaluated by Manufacturer or Contractor Hired by Manufacturer (by Noel Brinkerhoff, AllGov )
Federal Agencies with Guns: Weather Service, Social Security, Railroad Retirement Board
By Noel Brinkerhoff | AllGov | June 10, 2014
Thousands of federal government employees are armed with handguns and even semiautomatic and automatic weapons as part of their jobs for agencies that are not traditional law enforcement operations.
These gun-toting civil servants include those performing missions that involve Social Security, delivering the mail, predicting the weather, and overseeing railroad pensions. Others authorized to carry firearms conduct audits for the U.S. Department of Agriculture.
The Social Security Administration has sought to purchase 174,000 rounds of hollow-point bullets, while at least nine agencies have their own SWAT (Special Weapons and Tactics) teams, including the Office of Personnel Management, the Department of Labor, the National Aeronautics and Space Administration, the Department of Health and Human Services, the Food and Drug Administration, the Consumer Product Safety Commission, and the Fish and Wildlife Service.
With the increase of federal regulatory criminal laws being passed, the number of law-enforcement personnel attached to agencies has gone up as well. But the traditional law enforcement agencies like the Federal Bureau of Investigation and the Marshals Service have been unable to handle all of the demand to execute potentially dangerous investigations, searches and arrests, leading officials at these other departments to develop their own police forces, according to an analysis by Candice Bernd of Truthout.
These forces can take their jobs too seriously. In 2003, Department of Fish and Wildlife agents stormed into the home of George and Kathy Norris of Houston. George Norris imported and sold orchids. He was subsequently accused of smuggling a certain variety of the plant into the United States. Although it was later found that he had only made a few paperwork errors, he ended up pleading guilty to seven counts of violating the Endangered Species Act and served 17 months in prison.
Some lawmakers are starting to think it might be time to scale back on federal criminal codes. Last year, the Over-Criminalization Task Force (part of the House Judiciary Committee) convened for the first time to consider ways to shrink the number of laws and provisions on the books.
To Learn More:
USDA and Submachine Guns: Latest Example of Mission Creep as Federal Policing Expands (by Candice Bernd, Truthout)
Orchid Kingpin? Mistake Lands Elderly Gardener in Prison (by John Jessup, CBN News)
Manufacturer Tried to Hide Results of Testing of Blood Thinner Implicated in 1,000 Deaths
By Steve Straehley | AllGov | February 9, 2014
The manufacturer of a blood-thinning drug tried to hide results of an internal study that the manufacturer feared would hurt sales of the widely-advertised medication, according to recently-unsealed court documents.
Boehringer Ingelheim, manufacturer of Pradaxa, is being sued by patients and their families, charging it failed to properly warn users about possible dangers of the drug. More than 1,000 of those using Pradaxa have died from bleeding, Katie Thomas of The New York Times reported.
Some of the papers released by Chief Judge David R. Herndon of the United States District Court in East St. Louis, Ill., indicated that a research paper would contradict the company’s claims that regular blood monitoring is not necessary while taking Pradaxa. The lack of regular monitoring is one of the main selling points of the drug over warfarin, a drug long used in the prevention of blood clots and strokes. Warfarin requires frequent blood monitoring and attention to diet.
Boehringer Ingelheim emails released by the court show concern about the effect a change in recommended monitoring would have on sales of Pradaxa. “This may not be a onetime test and could result in a more complex message (regular monitoring), and a weaker value proposition … vs. competitors,” one employee wrote.
An email from another employee expressed concern about the drug’s safety risks in older patients, and said “there may be a role” for one or two blood tests in Pradaxa patients.
The case highlights the fact that much of the research on drugs is performed by the drug makers themselves, who have a financial interest in ensuring their products are approved by regulators.
The research paper, written by Paul A. Reilly, a clinical program director at Boehringer Ingelheim, found that some patients absorb too little of the drug to prevent strokes. It also said another group absorbs so much that they are at a higher risk for bleeding. These issues could be addressed with blood monitoring to ensure that patients have the proper levels of the drug in their bloodstream. Draft versions of the paper gave optimal levels of Pradaxa in a patient’s bloodstream.
Reilly’s paper was published in the February 2014 issue of the Journal of the American College of Cardiology, but some of the conclusions about blood monitoring that appeared in the draft version aren’t in the final report.
In a statement, Boehringer Ingelheim said the unsealed documents “represent small fragments of the robust discussion and debate that is a vital component in all scientific inquiry, and in the research and development of any important medication such as Pradaxa.”
One company supervisor, Dr. Jutta Heinrich-Nols, warned that publishing Reilly’s paper could make it “extremely difficult” for the company to defend its claims that Pradaxa did not require regular blood monitoring, the Times said.
In addition, there is so far no antidote to Pradaxa’s effects. With warfarin, physicians can administer doses of Vitamin K to counteract that drug’s effects in case a patient starts hemorrhaging.
The Justice Department has previously cited the company for intentionally making “unsubstantiated claims about the efficacy” of their drug Aggrenox, which is intended to prevent subsequent strokes, or strokes due to blood clots.
The Pradaxa documents were released the same week that Physicians for Integrity in Medical Research sued the Food and Drug Administration over the heart medication roflumilast, claiming it should be pulled off the market. The drug, made by Forest Laboratories and intended to treat chronic obstructive pulmonary disease (COPD), does more harm than good, according to the plaintiff.
To Learn More:
Study of Drug for Blood Clots Caused a Stir, Records Show (by Katie Thomas, New York Times)
New Emails in Pradaxa Case Show Concern Over Profit (by Katie Thomas, New York Times)
A Promising Drug With a Flaw (by Katie Thomas, New York Times)
Pradaxa Manufacturer Has History of Illegal Activities, Ties To Controversial Groups (by Alisha Mims, Ring of Fire)
Doctors Group Sues FDA to Withdraw Approval of Heart Drug (by Noel Brinkerhoff, AllGov)
America’s most popular prescription sleep medication linked to mass shootings
RT | January 20, 2014
A new report describing the bizarre and dangerous side effects of the sleep aid Ambien has once again raised questions about one of the United States’ most popular prescription drugs.
In a story by the Fix, Allison McCabe chronicled the numerous cases in which Ambien has caused individuals to commit unsafe, and sometimes deadly acts.
In 2009, 45-year-old Robert Stewart was convicted on eight charges of second-degree murder after he killed eight people in a nursing home. He was originally charged with first-degree murder, but by claiming his tirade was Ambien-induced he was able to have the charges lessened and sentenced to 142-179 years in prison.
In a similar case, Thomas Chester Page of South Carolina was sentenced on five counts of attempted murder despite his claims that Ambien was the cause of a shootout with officers. He received 30 years of prison on each count, to be served concurrently.
Although the Food and Drug Administration approved Ambien in 1992, its warning labels have changed significantly over the last two decades as evidence mounted documenting the drug’s ability to induce dangerous behavior.
“After taking AMBIEN, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing,” the label currently reads. “The next morning, you may not remember that you did anything during the night… Reported activities include: driving a car (“sleep-driving”), making and eating food, talking on the phone, having sex, sleep-walking.”
In the courtroom, cases related to Ambien use have ranged from shootings to child molestation charges to car accidents. In one such case, flight attendant Julie Ann Bronson from Texas ran over three people – including an 18-month old who suffered from brain damage as a result. When Bronson woke up in jail the next morning, she could barely comprehend what she had done.
“It was surreal. It was like a bad dream,” she said in May 2012. “I did the crime but I never intended to do it. I wouldn’t hurt a flea. And if I would have hit somebody, I would have stopped and helped. We’re trained in CPR.” Bronson pleaded guilty to the felony charges, but also received lesser charges by citing Ambien as the reason for her actions.
While some drug companies work on sleep aids that do not induce the kind of unpredictable and risky behavior Ambien does, the popularity of the medication raises concern over America’s prescription drug culture. The market for sleeping pills is a billion-dollar industry, yet dangerous side effects continue to be reported.
Last year, a report by the Department of Health and Human Services highlighted about 2,200 doctors for suspicious activities such as over-prescribing drugs. More than 700 Medicare doctors were also flagged for issuing what could be seen as “extreme” and potentially harmful prescriptions.
Although the report noted that some prescriptions could have been effective, it added, “prescribing high amounts on any of these measures may indicate that a physician is prescribing drugs which are not medically necessary or that he or she has an inappropriate incentive, such as a kickback, to order certain drugs.”
Soon after that report was issued, the Centers for Disease Control and Prevention found that roughly 18 women a day are dying in the United States due to prescription drug overdose, namely from painkillers like Vicodin and Oxycontin. With women making up 40 percent of all overdose deaths in 2010, these numbers marked a 400 percent increase compared to data from 1999.
The benefits of medication have also been placed under heavy scrutiny when it comes to other health issues, such as attention deficit hyperactivity disorder (ADHD). In December 2013, RT reported that the authors of the primary study promoting medication over behavioral therapy in order to treat ADHD now have serious concerns over their original results.
“I hope it didn’t do irreparable damage,” said one of the stud’s co-authors, Dr. Lilly Hechtman of Montreal’s McGill University. “The people who pay the price in the end is the kids. That’s the biggest tragedy in all of this.”
FDA Antibiotic Guidance Is Gift To Big Pharma and Big Meat
By Martha Rosenberg | Dissident Voice | December 23, 2013
This month’s FDA guidance for reducing livestock antibiotics will actually make things worse, animal welfare and food activist groups are saying. “The FDA is using a garden hose on a forest fire,” says Farm Sanctuary Senior Policy Director Bruce Friedrich. The guidance is a “diversion” that pretends to address the problem of factory farm-driven antibiotic resistance while accomplishing nothing. Antibiotic resistant infections, widely seen as driven by factory farming, sicken 2 million a year in the US and kill 23,000, says the CDC. By asking drug makers to voluntarily renounce the use of antibiotics for livestock growth on their labels, the guidance “won’t cost the industry a penny” or reduce antibiotic use at all, says Friedrich. The reason? Factory farm antibiotics are also used to treat sickness which the crowded conditions tempt — a use that is still allowed under the guidance. Only the wording will change, says Friedrich.
In a December 11 conference call, the FDA’s Michael (“Monsanto”) Taylor, deputy commissioner for foods and veterinary medicine, William T. Flynn, deputy director for science policy and USDA’s Thomas J. Myers, associate deputy administrator, told reporters that the government is asking drug makers to voluntarily restrict the uses on their antibiotic labels –yes, asking – in a shocking gift of self-regulation. Similar honor systems exist at slaughterhouses since Hazard Analysis and Critical Control Points (HACCP) was instituted in 1998 in which industry creates its own safety plan which the government simply cosigns. A similar honor system called the Hazard Analysis and Critical Control Point-Based Inspection Models Project (HIMP) is imminent for poultry slaughterhouses.
Why are the FDA and USDA allowing industry to write its own ticket? (And why would industry write itself out of its own profits?) Because to mandate the changes would require “hundreds of separate regulations” and actions, whined government officials on the conference call. It is easier to just say please to industry.
To many reporters on the conference call, the plans sounded like fluff. If the changes are voluntary, “what will enforce” them and serve as an “incentive” asked an ABC reporter? Food producers and drug companies need no incentive retorted Michael Taylor because they are starting to phase out antibiotics “for their own reasons” — citing McDonald’s and KFC. Right.
If factory farmers actually phased out antibiotics (which prevent animals from becoming sick in high density-farming) won’t livestock producers “have to move to different buildings” asked a reporter from Reuters. That’s why we are giving industry three years to comply replied William Flynn.
Will you release the identifies of drug companies who do not comply asked another reporter? No, replied Flynn. We will give an “overview” of the level of “engagement” of industry but not individual company names. (USDA has also protected the identities of US ranches that released mad cows into the US food supply and restaurants who served them according to newspaper and government sources.)
Animal welfare groups like Farm Sanctuary, American Society for the Prevention of Cruelty to Animals and the Animal Legal Defense Fund are not the only ones calling the FDA guidance toothless and a serious capitulation to industry. Congresswoman Louise M. Slaughter, the only microbiologist in Congress, called the guidance “an inadequate response to the growing antibiotic resistant crisis caused by overuse of antibiotics on the farm.” Industry has spent over $17 million to block a bill Rep. Slaughter developed, in conjunction with the late Sen. Ted Kennedy, called the Preservation of Antibiotics for Medical Treatment Act (PAMTA), says a press release from her office.
This is not the first time government has caved to drug makers over the regulation of livestock antibiotics. In 2008, the FDA had announced that there was “evidence that extralabel use of these drugs [cephalosporins] in food-producing animals will likely cause an adverse event in humans and, as such, presents a risk to the public health,” and called for their prohibition. Notice the FDA says “will likely cause” not “could likely cause” and “presents a risk” not “could present a risk”?
But by the time hearings were held two months later and lobbyists had worked their magic, the “Cephalosporin Order of Prohibition” had somehow become a “Hearing to Review the Advances In Animal Health Within The Livestock Industry.” Prohibition — advances, same idea, right?
At the hearings, the American Veterinary Medical Association (AVMA), the Animal Health Institute, a Big Pharma trade group and the egg, chicken, turkey, milk, pork and cattle industries whined that they could not “farm” without antibiotics because more feed would be required and the animals would get sick from being immobilized over their own manure.
Afterwards, W. Ron DeHaven, DVM, who was the USDA’s top vet before leaving for industry and helming the AVMA, penned a rambling, almost incoherent 18-page letter with 62 footnotes to the FDA. Cephalosporin resistant “human pathogens” aren’t increasing, says the letter, and even if they are, they’re not affecting human health, and even they’re affecting human health, how do you know it’s from the livestock drugs, and even if it’s from the livestock drugs, the FDA has no legal authority to ban cephalosporin. Got that?
Alternately maudlin and accusatory, the letter plays on terrorism fears by calling a cephalosporin ban a “food security issue” affecting “the number of animals available for the food supply.” It also plays on humanitarian sentiments by claiming a ban would impede veterinarians’ ability “to relieve the pain and suffering of animals” as if cephalosporins are pain killers and other drugs aren’t available. (And as if antibiotics are given for animals’ welfare instead of revenue welfare!) But less than a month after the letter was sent, on November 25 the FDA quietly revoked the prohibition. Good hire, AVMA!
It is no surprise that factory farm operators fight to keep their antibiotics says Farm Sanctuary’s Bruce Friedrich. Without them, in their profit-driven “filth chambers,” the animals would simply die.
Drug Companies and Doctors Boost Profits Pitching Attention Deficit Disorder
By Noel Brinkerhoff | AllGov | December 17, 2013
With the help of physicians, pharmaceutical makers have made billions of dollars peddling medicines to treat attention deficit disorder, leading some experts, and even one pharmaceutical executive, to declare that the marketing push has gone too far.
Last year, sales of stimulant medication intended to treat attention deficit hyperactivity disorder (ADHD) reached $9 billion—a fivefold increase from a decade ago.
Today, 15% of high school students have been diagnosed with ADHD, with about 3.5 million of them on some sort of drug marketed to treat the disorder.
Dr. Keith Conners, who has spent decades trying to help children with ADHD, has questioned the increasing rates of diagnosis, calling them “a national disaster of dangerous proportions.”
“The numbers make it look like an epidemic. Well, it’s not. It’s preposterous,” Conners, a psychologist and professor emeritus at Duke University, told The New York Times. “This is a concoction to justify the giving out of medication at unprecedented and unjustifiable levels.”
The drug industry has worked for two decades to publicize ADHD and promote its remedies to doctors, educators and parents. As a result, the disorder is now the second most frequent long-term diagnosis made in children, just behind asthma.
Drugs such as Ritalin, Adderall, Concerta, Focalin, Vyvanse, Intuniv and Strattera have been promoted to help children, but along the way, the Food and Drug Administration has cited every major ADHD drug for false and misleading advertising since 2000.
Doctors also have been criticized for taking money from drug companies to publish research and deliver presentations that encourage colleagues to prescribe these drugs, which possess significant side effects and are regulated in the same class as morphine and oxycodone because of their potential for abuse and addiction.
Now, companies want to market the medications to adults to further expand revenue-making opportunities.
Roger Griggs, the pharmaceutical executive who introduced Adderall in 1994, objects to marketing stimulants to the general public because of the risks involved. He called the drugs “nuclear bombs” that should rarely be prescribed and carefully monitored by a treating physician, according to the Times.
To Learn More:
The Selling of Attention Deficit Disorder (by Alan Schwarz, New York Times)
Latest Condition Invented by Drug Companies…Low Testosterone (by Matt Bewig, AllGov)
Drug Companies Increase Profits by Creating Fear of Diseases (and Even Diseases) (by David Wallechinsky, AllGov)
US makes first step toward banning trans fats
RT | November 7, 2013
The Food and Drug Administration announced on Thursday that it would require the food industry to phase out the use of artificial trans fats in its products.
The FDA said it has made a preliminary determination that the primary source of trans fat – partially hydrogenated oils – is no longer “generally recognized as safe,” and that it plans to ban their use in the market. Some trans fat is naturally generated in meat and dairy products, and the ban will only apply to trans fat added to foods.
According to FDA Commissioner Margaret Hamburg, the decision could potentially prevent 20,000 heart attacks a year and 7,000 deaths.
Over the last decade, American consumption of trans fat has declined significantly. In 2006, the average citizen was consuming 4.6 grams of trans fat a day, while the number decreased to roughly one gram a day in 2012. Still, Hamburg said they “remain an area of significant public health concern,” according to NBC News.
Many companies began eliminating the use of trans fat when the FDA required them to list the ingredient on nutritional labels in 2006, but it can still be found in common products like frozen pizza, microwave popcorn, margarine, coffee creamer, and various desserts.
“The artery is still half clogged,” Dr. Thomas Frieden, the director of the Centers for Disease Control and Prevention, said to the New York Times. “This is about preventing people from being exposed to a harmful chemical that most of the time they didn’t even know was there.”
“It’s quite important,” he added, referring to the FDA’s new proposal. “It’s going to save a huge amount in health care costs and will mean fewer heart attacks.”
Numerous studies have shown that there is virtually no health benefit to consuming trans fat. It lowers the level of “good” cholesterol and raises levels of “bad” cholesterol, clogging the arteries and increasing the risk of heart attacks.
The FDA did not lay out a timetable for the ban. It will open its proposal to public comment for 60 days while it formulates a schedule that gives food manufacturers enough time to cooperate with the new rule.
“We want to do it in a way that doesn’t unduly disrupt markets,” Michael Taylor, the FDA’s deputy commissioner for foods, said to the Associated Press. At the same time, he said the food “industry has demonstrated that it is by and large feasible to do.”
Public health groups have welcomed the FDA’s proposal, which the agency has been collecting data for since 2009.
Should the FDA move forward with its plan, the United States will join other nations such as Denmark, Iceland, and Switzerland, in banning the ingredient.
Still, there are numerous other ingredients that have been outlawed in various countries while still being sold in the U.S. An, article by BuzzFeed over the summer noted that brominated vegetable oil, which has been linked to birth defects and organ damage, continues to be used in sports drinks and the popular soda Mountain Dew. It’s been banned in more than 100 countries.
Meanwhile, synthetic hormones rGBH and rBST, linked to cancer and infertility, continue to be given to cows and show up in dairy products that aren’t labeled otherwise. They’ve been banned in Japan, Canada, New Zealand, Australia, and the European Union.
Earlier this month, the FDA banned three out of the four brands of arsenic-laced animal feed that was being given to chickens, turkeys, and pigs. The decision came four years after the Center for Food Safety called on the FDA to remove the feed, but one brand remains on the market.
Related article
Failure to Curb Use of Antibiotics in Livestock Signals Danger for Humans
By Noel Brinkerhoff | AllGov | October 24, 2013
Despite repeated warnings from experts, the federal government under President Barack Obama has continued to allow farmers to pump livestock with antibiotics intended for humans, which has increased health risks for Americans.
A new study (pdf) from the Johns Hopkins Center for a Livable Future (JHCLF) blamed the lack of meaningful change in livestock-antibiotics policies on the agricultural and pharmaceutical industries, which have lobbied to block new laws and regulations from being adopted.
Members of Congress and officials with the Food and Drug Administration (FDA) have caved to industry pressures, even though evidence shows the overuse of antibiotics in livestock has made these drugs less effective in treating human infections.
Bob Martin, executive director of the JHCLF, told The Washington Post that FDA statistics reveal as much as 80% of the antibiotics sold in the U.S. are fed to cattle, pigs, chickens and other farm animals—a practice that reduces the efficacy of the drugs when it comes to fighting deadly infections in people.
Currently, about 23,000 patients die from antibiotic-resistant infections each year, according to the Centers for Disease Control and Prevention.
The Johns Hopkins study echoed the concerns of a 2008 report (pdf) on industry practices by a Pew Charitable Trusts commission of scientists that involved the Johns Hopkins Bloomberg School of Public Health. This earlier study also warned that the nation must back off on feeding antibiotics to animals.
The FDA has developed new guidelines that would require farms to stop using antibiotics specifically to bulk up food animals. But the rules would allow the drugs’ continued use for disease control. This latter provision is so loosely defined, Martin said, that there would be no practical change in the use of antibiotics.
“In a couple of areas, the Obama administration started off with good intentions. But when industry pushed back, even weaker rules were issued,” he told the Post. “We saw undue influence everywhere we turned.”
The new report was authored by a commission chaired by former Kansas governor John Carlin (D) and that included former U.S. agriculture secretary Dan Glickman, ranchers, and experts in public health and veterinary medicine.
The report’s message was echoed in a dire warning issued by Mary Wilson of the Harvard School of Public Health: “We will see common infections become fatal,” just as they were before the invention of antibiotics, she told the Post.
To Learn More:
Report: Feeding Antibiotics to Livestock is Bad for Humans, but Congress Won’t Stop It (by Melinda Henneberger, Washington Post)
Industrial Food Animal Production in America: Examining the Impact of the Pew Commission’s Priority Recommendations (John Hopkins Center for a Livable Future) (pdf)
FDA Quietly Ends Attempt to Regulate Antibiotics in Animal Feed (by Noel Brinkerhoff, AllGov)
80% of U.S. Antibiotics Go to Farm Animals (by Noel Brinkerhoff, AllGov)
FDA Let Drugs Approved on Fraudulent Research Stay on the Market
Retired FDA investigator Patrick Stone (Katie Hayes Luke for ProPublica)
By Charles Seife and Rob Garver | ProPublica | April 15, 2013
On the morning of May 3, 2010, three agents of the Food and Drug Administration descended upon the Houston office of Cetero Research, a firm that conducted research for drug companies worldwide.
Lead agent Patrick Stone, now retired from the FDA, had visited the Houston lab many times over the previous decade for routine inspections. This time was different. His team was there to investigate a former employee’s allegation that the company had tampered with records and manipulated test data.
When Stone explained the gravity of the inquiry to Chinna Pamidi, the testing facility’s president, the Cetero executive made a brief phone call. Moments later, employees rolled in eight flatbed carts, each double-stacked with file boxes. The documents represented five years of data from some 1,400 drug trials.
Pamidi bluntly acknowledged that much of the lab’s work was fraudulent, Stone said. “You got us,” Stone recalled him saying.
Based partly on records in the file boxes, the FDA eventually concluded that the lab’s violations were so “egregious” and pervasive that studies conducted there between April 2005 and August 2009 might be worthless.
The health threat was potentially serious: About 100 drugs, including sophisticated chemotherapy compounds and addictive prescription painkillers, had been approved for sale in the United States at least in part on the strength of Cetero Houston’s tainted tests. The vast majority, 81, were generic versions of brand-name drugs on which Cetero scientists had often run critical tests to determine whether the copies did, in fact, act the same in the body as the originals. For example, one of these generic drugs was ibuprofen, sold as gelatin capsules by one of the nation’s largest grocery-store chains for months before the FDA received assurance they were safe.
The rest were new medications that required so much research to win approval that the FDA says Cetero’s tests were rarely crucial.
Stone said he expected the FDA to move swiftly to compel new testing and to publicly warn patients and doctors.
Instead, the agency decided to handle the matter quietly, evaluating the medicines with virtually no public disclosure of what it had discovered. It pulled none of the drugs from the market, even temporarily, letting consumers take the ibuprofen and other medicines it no longer knew for sure were safe and effective. To this day, some drugs remain on the market despite the FDA having no additional scientific evidence to back up the safety and efficacy of these drugs.
By contrast, the FDA’s transatlantic counterpart, the European Medicines Agency, has pulled seven Cetero-tested medicines from the market.
The FDA also has moved slowly to shore up the science behind the drugs. Twice the FDA announced it was requiring drug makers to repeat, reanalyze or audit many of Cetero’s tests, and to submit their findings to the agency. Both times the agency set deadlines, yet it has allowed some companies to blow by them.
Today, six months after the last of those deadlines expired and almost three years after Cetero’s misconduct was discovered, the FDA has received the required submissions for just 53 drugs. The agency says most companies met the deadlines but acknowledged that “a few have not yet submitted new studies.”
Other companies, it said, have not submitted new research because they removed their drugs from the market altogether.
For its part, the FDA has finished its review of just 21 of the 53 submissions it has received, raising the possibility that patients are taking medications today that the agency might pull off the market tomorrow.
To this day, the agency refuses to disclose the names of the drugs it is reassessing, on the grounds that doing so would expose “confidential commercial information.” ProPublica managed to identify five drugs that used Cetero tests to help win FDA approval.
FDA officials defended the agency’s handling of the Cetero case as prudent and scientifically sound, noting that the agency has found no discrepancies between any original drug and its generic copy and no sign that any patients have been harmed.
“It is non-trivial to have to redo all this, to withdraw drugs, to alarm the public and the providers for a large range of drugs,” said Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research. “There are consequences. To repeat the studies requires human experimentation, and that is not totally without risk.”
Woodcock added that an agency risk assessment found the potential for harm from drugs tested by Cetero to be “quite low,” an assessment she said has been “confirmed” by the fact that no problems have been found in the drugs the agency has finished reviewing.
She declined to release the risk assessment or detail its design. A subsequent statement from the agency described the assessment as “fluid” and “ongoing.” The FDA also has not released its 21 completed reviews, which ProPublica has requested.
Some experts say that by withholding so much information in the Cetero case the FDA failed to meet its obligations to the public.
“If there are problems with the scientific studies, as there have been in this case, then the FDA’s review of those problems needs to be transparent,” said David Kessler, who headed the FDA from 1990 to 1997 and who is now a professor at the University of California at San Francisco. Putting its reviews in public view would let the medical community “understand the basis for the agency’s actions,” he said. “FDA may be right here, but if it wants public confidence, they should be transparent. Otherwise it’s just a black box.”
Another former senior FDA official, who spoke on condition of anonymity, also felt the FDA had moved too slowly and secretively. “They’re keeping it all in the dark. It’s not transparent at all,” he said.
By contrast, the European Medicines Agency has provided a public accounting of the science behind all the drugs it has reviewed. Its policy, the EMA said in response to questions, is to make public “all review procedures where the benefit-risk balance of a medicine is under scrutiny.”
Woodcock dismissed comparisons to the EMA. “Europe had a smaller handful of drugs,” she said, “and they may not have engaged in as extensive negotiation and investigations with the company as we did.”
She said the FDA would have disclosed more, including the names of drugs, had it believed there was a risk to public health. “We believe that this did not rise to the level where the public should be notified,” she said. “We felt it would result in misunderstanding and inappropriate actions.”
In a written response to Kessler’s comments, the FDA said, “We’ve been as transparent as possible given the legal protections surrounding an FDA investigation of this or any type. The issue is not a lack of transparency but rather the difficulty of explaining why the problems we identified at Cetero, which on their face would appear to be highly significant in terms of patient risk, fortunately were not.”
Still, the FDA’s secrecy has had other ramifications. Some of Cetero’s suspect research made its way unchallenged into the peer-reviewed scientific literature on which the medical community relies. In one case, a researcher and a journal editor told ProPublica they had no idea the Cetero tests had been called into doubt.
Cetero, in correspondence with the FDA, conceded misconduct. And in an interview, Cetero’s former attorney, Marc Scheineson, acknowledged that chemists at the Houston facility committed fraud but said the problem was limited to six people who had all been fired.
“There is still zero evidence that any of the test results…were wrong, inaccurate, or incorrect,” he said. Scheineson called the FDA’s actions “overkill” and said they led to the demise of Cetero and its successor company.
In 2012, the company filed for Chapter 11 bankruptcy and emerged with a new name, PRACS Institute. PRACS, in turn, filed for bankruptcy on March 22 of this year. A PRACS spokesperson said the company had closed the Houston facility in October 2012.
Pamidi, the Cetero executive who provided the carts of file boxes, declined to comment.
As for Stone, the former FDA investigator, he said he was disturbed by the agency’s decisions.
“They could have done more,” he said. “They should have done more.”
‘We Should Have Been Told’
Cross-checking U.S. and European public records, including regulatory filings, scientific studies and civil lawsuits, ProPublica was able to identify a few of the drugs that are on the U.S. market because of tests performed at Cetero’s Houston lab (see chart.) There is no evidence that patients have suffered harm from these drugs; the FDA says it has detected no increase in reports of side effects or lack of efficacy among Cetero-tested medications.
To be sure, just because a crucial study is deemed potentially unreliable does not mean that a drug is unsafe or ineffective. What it does mean is that the FDA’s scientific basis for approving that drug has been undermined.
The risks are real, academic experts say, particularly for drugs such as blood thinners and anti-seizure medications that must be given at very specific doses. And generic versions of drugs have been known to act differently from name-brand products (see accompanying story.)
There is no indication the generic ibuprofen gelatin capsules hurt anyone, but their case shows how the FDA left a drug on the market for months without confirmation that the drug was equivalent to the name brand.
The capsules were manufactured by Banner Pharmacaps and carried by Supervalu, a grocery company that operates or licenses more than 2,400 stores across the United States, including Albertson’s, Jewel-Osco, Shop ‘n Save, Save-A-Lot, and Shoppers Food & Pharmacy.
Cetero had performed a key analysis to show that the capsules were equivalent to other forms of the drug. Banner, the drug’s maker, said the FDA first alerted it to the problems at Cetero in August 2011. The FDA required drug companies to redo many of Cetero’s tests, but, a spokesperson for Banner wrote in an email, “We received no directive from FDA to recall or otherwise interrupt manufacture of the product.”
Banner said it repeated the tainted Cetero tests at a different research firm, and the FDA said it received the new data in January 2012 — leaving a gap of at least five months when the FDA knew the drug was on the market without a rock-solid scientific basis.
An FDA spokesperson wrote in an email that the agency found the new studies Banner submitted “acceptable” and told Banner it had no further questions.
A spokesperson for Supervalu told ProPublica it purchased the ibuprofen from a supplier, which has assured the grocery company that “there are no issues with the product.”
According to U.S. and European records, another one of the drugs approved based on research at Cetero’s troubled Houston lab was a chemotherapy drug known as Temodar for Injection.
Temodar was originally approved in 1999 as a capsule to fight an aggressive brain cancer, glioblastoma multiforme. Some patients, however, can’t tolerate taking the medication orally, so drug maker Schering-Plough decided to make an intravenous form of the drug.
To get Temodar for Injection approved, the FDA required what it called a “pivotal” test comparing the well-established capsule form of Temodar to the form injected directly into the bloodstream.
Cetero Houston conducted that test, comparing blood samples of patients who received the capsule to samples of those who got the injection to determine if the same amount of the drug was reaching the bloodstream. This test is crucial, particularly in the case of Temodar, where there was a question about the right dosing regimen of the injectable version. If too little drug gets into the blood, the cancer could continue to grow unabated. If too much gets in, the drug’s debilitating side effects could be even worse.
Cetero performed the test between September 2006 and October 2007, according to documents from the European Medicines Agency, and FDA records indicate that same test was used to win approval in the U.S.
In 2011, the FDA notified Merck & Co., which had acquired Schering-Plough, about the problems with Cetero’s testing. In April 2012, the FDA publicly announced that analyses done by Cetero during the time when it performed the Temodar work would have to be redone. But according to Merck spokesman Ronald Rogers, the FDA has not asked Merck for any additional analyses to replace the questionable study.
The FDA declined to answer specific questions about the Temodar case, saying to do so would reveal confidential commercial information. But Woodcock said that in some cases, drug manufacturers had submitted alternative test results to the FDA that satisfied the agency that no retesting was necessary for specific drugs.
The FDA never removed Temodar for Injection from the market. The European Medicines Agency also kept the injection form of the drug on the market, but the two agencies handled their decision in sharply different ways.
The EMA has publicly laid out evidence — including studies not performed by Cetero — for why it believes the benefits of the injection drug outweigh its risks. But in the United States, the FDA has kept silent. To this day, Temodar’s label — the single most important way the FDA communicates the risks and benefits of medication — still displays data from the dubious Cetero study. (The label of at least one other drug, a powerful pain reliever marketed as Lazanda, also still displays questionable Cetero data.)
Woodcock said the agency hadn’t required manufacturers to alter their labels because, despite any question about precise numerical precision, the FDA’s overall recommendation had not changed.
In a written response to questions, Merck said it “stands behind the data in the TEMODAR (temozolomide) label.” The company said it learned about “misconduct at a contract research organization (CRO) facility in Houston” from the FDA and that it cooperated with investigations by the FDA and its European counterpart. It said that Cetero had performed no other studies for Merck.
Even one of the researchers involved in evaluating injectable Temodar didn’t know that the FDA had flagged Cetero’s analysis as potentially unreliable until contacted by a reporter for this story.
Dr. Max Schwarz, an oncologist and clinical professor at Monash University in Melbourne, Australia, treated some brain-cancer patients with the experimental injectable form of Temodar and others with the capsule formulation. Blood from his patients was sent to Cetero’s Houston lab for analysis.
Schwarz said he still has confidence in the injectable form of the drug, but said that he was “taken aback” when a reporter told him that the FDA had raised questions about the analysis. “I think we should have been told,” he said.
Suspect research conducted by Cetero Houston was not only used to win FDA approval but was also submitted to peer-reviewed scientific journals. Aided by the FDA’s silence, those articles remain in the scientific literature with no indication that they might, in fact, be compromised. For example, based on Cetero’s work, an article in the journal Cancer Chemotherapy and Pharmacology purports to show that Temodar for Injection is equivalent to Temodar capsules.
Edward Sausville, co-editor-in-chief of the journal, said in an email that the first he heard that something might be wrong with the Cetero research was when a reporter contacted him for this story. He also said the publisher of the journal would conduct a “review of relevant records pertinent to this case.”
‘There’s Always Something Missing’
During his years of inspecting the Houston lab, the FDA’s Stone said he often had the sense that something wasn’t right. When he went to other contract research firms and asked for data on a trial, they generally produced an overwhelming amount of paper: records of failed tests, meticulous explanations of how the chemists had made adjustments, and more.
Cetero’s records, by contrast, showed very clean, error-free procedures. As Stone and his colleagues dug through the data, though, they often found gaps. When pressed, Cetero officials would often produce additional data — data that ought to have been in the files originally handed over to the FDA.
Stone said, “We should have looked back and said, ‘Wait a minute, there’s always something missing from the studies from here. Why?'”
One reason, the FDA would determine, was that Cetero’s chemists were taking shortcuts and other actions prohibited by the FDA’s Good Laboratory Practice guidelines, which set out such matters as how records must be kept and how tests must be performed.
Stone and his FDA colleagues might never have realized Cetero was engaging in misconduct if a whistleblower hadn’t stepped forward.
Cashton J. Briscoe operated a liquid chromatography-tandem mass spectrometry device, or “mass spec,” a sensitive machine that measures the concentration of a drug in the blood.
He took blood samples prepared by Cetero chemists and used mass specs to perform “runs” — tests to see how much of a drug is in patients’ blood — that must always be performed with control samples. Often those controls show readings that are clearly wrong, and chemists have to abort runs, document the failure, recalibrate the machines, and redo the whole process.
But Cetero paid its Houston chemists based on how many runs they completed in a day. Some chemists doubled or even tripled their income by squeezing in extra tests, according to time sheets entered as evidence in a lawsuit filed in U.S. District Court in Houston by six chemists seeking overtime payments. Briscoe thought several chemists were cutting corners — by using the control-sample readings from one run in other runs, for example.
Attorney Scheineson, who represented Cetero during the FDA’s investigation, acknowledged that the Houston lab’s compensation system was “crappy” and that a handful of “dishonest” chemists at the Houston facility committed fraud.
In April 2009, Briscoe blew the whistle in a letter to the company written by his lawyer, reporting that “many of the chemists were manipulating and falsifying data.” Soon thereafter, Briscoe told the company that he had documented the misconduct. According to Stone and documents reviewed by ProPublica, Briscoe had photographic evidence that mass spec operators had switched the quality control samples between different runs; before-and-after copies of documents with the dates and other material changed; and information about a shadow computer filing system, where data from failed runs could be stored out of sight of FDA inspectors.
On June 5, apparently frustrated with Cetero’s response, Briscoe went a step further and called the FDA’s Dallas office. He agreed to meet Stone the following Monday, but never showed. Stone called him, as did other FDA officials, but Briscoe had changed his mind and clammed up.
Still, Stone’s brief phone conversation with Briscoe reminded the agent of all those suspiciously clean records he had seen at Cetero over the years. “Now that you have a bigger picture,” Stone recalled, “you’re like, ‘Oh, some of this stuff is cooked.'”
Two days after Stone’s aborted meeting with Briscoe, Cetero informed the FDA that an employee had made allegations of misconduct and that the company had hired an outside auditor to review five years’ worth of data. That led to months of back-and-forth between the agency and Cetero that culminated when Stone and his inspectors arrived in Houston in May 2010.
Two teams of FDA investigators eventually confirmed Briscoe’s main allegations and cited the company for falsifying records and other violations of Good Laboratory Practice. The net effect of the misconduct was far-reaching, agency officials wrote in a July 2011 letter:
“The pervasiveness and egregious nature of the violative practices by your firm has led FDA to have significant concerns that the bioequivalence and bioavailability data generated at the Cetero Houston facility from April 1, 2005, to June 15, 2010 … are unreliable.”
Bioequivalence studies measure whether a generic drug acts the same in the body as the name-brand drug; bioavailability studies measure how much drug gets into a patient’s system.
The FDA’s next step was to try to determine which drugs were implicated — information the agency couldn’t glean from its own records.
“We couldn’t really tell — because most of the applications we get are in paper — which studies were actually linked to the key studies in an application without asking the application holders,” the FDA’s Woodcock said. “So we asked the application holders,” meaning the drug manufacturers.
In the interim, the FDA continued to investigate processes and procedures at Cetero.
“We put their operations under a microscope,” said Woodcock. A team of clinical pharmacologists, statisticians and IT experts conducted a risk analysis of the problems at Cetero, she said, and they “concluded that the risk of a misleading result was very low given how the studies were done, how the data were captured and so forth.”
In April 2012, nearly three years after Briscoe first alerted the FDA to problems at Cetero, and nearly two years after Cetero handed over its documentation to inspectors, the FDA entered into a final agreement with the company. Drug makers would need to redo tests conducted at the company’s Houston facility between April 1, 2005 and Feb. 28, 2008, if those studies had been part of a drug application submitted to the FDA. If stored blood samples were still usable, they could be reanalyzed. If not, the entire study would need to be repeated, the FDA said. The agency set a deadline of six months.
Cetero tests done between March 1, 2008 and Aug. 31, 2009 would be accepted only if they were accompanied by an independent data integrity audit.
Analyses done after Sept. 1, 2009 would not require retesting. The FDA said that Cetero had issued a written directive on Sept. 1, 2009, ordering one kind of misconduct to stop, which was why it did not require any action on Cetero Houston studies after that date. According to public documents, however, the agency’s inspectors “found continued deficiencies” that persisted into December 2010.
In response to questions, the FDA said the problem period “was subsequently narrowed as more information regarding Cetero’s practices became available.”
A year after concluding its final agreement with Cetero, the FDA’s review is still not finished. “Without the process being public it’s hard to know, but it seems that this has been going on for too long,” said Kessler, the former FDA chief.
“The process has been long,” the FDA said, “because of the number of products involved and our wish to be thorough and accurate in both our requests for and our review of the data.”
Cetero’s attorney Scheineson said the FDA scaled back its requirements because it finally talked with company officials. He noted that Cetero had tried repeatedly to talk with the FDA before the agency issued its strongly worded July 2011 letter, and that more than 1,000 employees have since lost their jobs.
“If you would get an honest assessment from the leaders of the agency,” he said, “I think in retrospect they would have argued that this was overkill here and that they should have had input from the company before essentially going public with that death sentence.”
“I’m not sure what is meant by ‘death sentence,'” an FDA spokesperson wrote in response, “but our first priority was and is patient safety and we proceeded to conduct the investigation toward that objective.”
‘Should I Be Proud of This?’
The FDA’s Stone draws little satisfaction from unraveling the problems at Cetero.
There are thousands of bioequivalence studies done every year, he pointed out, with each study generating thousands of pages of paper records. “Do you really think we’re going to look at 100 percent of them? We’re going to look at maybe 5 percent if we’re lucky,” he said. “Sometimes 1 percent.”
Still, given how often he and other FDA teams had inspected the Houston lab, he thinks regulators should have spotted Cetero’s misconduct sooner.
“In hindsight I look back and I’m like, ‘Wow, should I be proud of this?'” he said. “It’s cool that I was part of it, but it’s crap that we didn’t catch it five years ago. How could we let this go so long?”
Rob Garver can be reached at rob.garver@propublica.org, and Charles Seife can be reached at cgseife@nasw.org.
Research assistance for this story was contributed by Nick Stockton, Christine Kelly, Lily Newman, Joss Fong and Sarah Jacoby of the Science, Health, and Environmental Reporting Program at NYU.