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.
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.
Retired FDA investigator Patrick Stone (Katie Hayes Luke for ProPublica)
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?”
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.
WASHINGTON – Dairy industry groups have asked the Food and Drug Administration to be able to put artificial sweeteners in milk, and not change the label, claiming that it is so consumers can “more easily identify its overall nutritional value”.
The Food and Drug Administration is asking for data related to those sweeteners.
The International Dairy Foods Association (IDFA) and the National Milk Producers Federation (NMPF) filed a petition in 2009 requesting that the FDA amend its standard of identity for milk.
The petition asked the agency to allow the use of “any safe and suitable” sweetener for milk and asked to amend the standards of identity for 17 other milk and cream products.
Those products include sweetened condensed milk, whipping cream, yogurt and eggnog, which the groups say should be allowed to have “safe and suitable” sweeteners.
The groups request that the FDA “allow optional characterizing flavoring ingredients used in milk (e.g. chocolate flavoring added to milk) to be sweetened with any safe and suitable sweetener – including non-nutritive sweeteners such as aspartame.”
FDA regulations currently only allow milk products to contain “nutritive sweeteners” (those with calories) which the agency generally recognizes as safe.
The groups say the amendments “would promote more healthful eating practices and reduce childhood obesity by providing for lower-calorie flavored milk products.”
“They state that lower-calorie flavored milk would particularly benefit school children who, according to IDFA and NMPF, are more inclined to drink flavored milk than unflavored milk at school,” the FDA wrote in its notice.
The groups also say they would help with programs that aim to improve nutrition in school meals and argue that the proposed amendments would promote “honesty and fair dealing in the marketplace,” the FDA wrote.
By JOE GIAMBRONE | December 21, 2012
Well, you probably don’t want to look at more than 60 different documented school shooters and stabbers who were on antidepressant drugs when they attacked innocent children in suicidal, violent outbursts. Not if your mind is already made up that “it’s the guns” and that yet another “gun control” law will suddenly fix things. It won’t. Nor will the congressional testimony of Dr. Peter Breggin on the dangers of SSRIs and the proven links to suicide and violent ideation interest you, as long as there is one factor, and one solution, and this sort of information doesn’t fit into your preconception.
If this latest psycho-killer boy, Adam Lanza, had stolen a car and run over 26 people, would the most glaring problem be not enough car regulations?
Or if he had chosen to run around with a chainsaw instead, would the call now be for more chainsaw control? Or would the focus have turned to just banning the Texas Chainsaw Massacre films?
Why do they do it?
More than a little evidence suggests that antidepressant medications, prescribed by psychiatrists – who have a vested stake in the public perception of this issue – are a contributing factor in the majority of such spree massacres. The drug corporations, which produce these medications and which pay for massive advertising campaigns on TV, in newspapers, on the radio and in magazines, certainly want their friendly press outlets to come up with a different culprit. However, the lengthy list of warnings, right on the labels of these drugs, is an indication that the links are real, not very well understood, and potentially catastrophic.
Even Time Magazine reported on links between prescription drugs and violence:
Desvenlafaxine (Pristiq) … 7.9 times more likely to be associated with violence than other drugs.
Venlafaxine (Effexor) … 8.3 times…
Fluvoxamine (Luvox) … 8.4 times…
Triazolam (Halcion) … 8.7 times…
Atomoxetine (Strattera) … 9 times…
Mefoquine (Lariam) … 9.5 times…
Amphetamines: (Various) … 9.6 times…
Paroxetine (Paxil) … 10.3 times…
Fluoxetine (Prozac) … 10.9 times…
Varenicline (Chantix) … 18 times… (Time)
As Dr. Breggin calls it on his website:
“Antidepressants cause emotional anesthesia and numbing or sometimes euphoria, providing a fleeting, artificial relief from emotional suffering. … In the long run, all psychiatric drugs tend to disrupt the normal processes of feeling and thinking, rendering the individual less able to deal effectively with personal problems and with life’s challenges. They worsen the individual’s overall mental condition and produce potentially irreversible harm to the brain.”
Breggin provided expert testimony and dire warnings to a congressional committee and cautioned against dispensing antidepressants to military personnel out of a very real fear of resulting violence by well-armed troops.
Even the FDA has had to impose stronger warnings on these “medicines” over the years, in response to the real world data. The 2007 update to the “Black Box” warnings, which are mandatory and included with all antidepressants says:
“Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. … Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.” (FDA, emphasis added)
The United States abandoned its mentally ill citizens back in the 1980s. Now they live under bridges. I see them with their tent city near my favorite Chinese restaurant. The great shining city on the hill doesn’t give a damn who’s living outdoors now. The stigma about mental illness has worked its way through the rest of society, but not in the obvious way.
People don’t reject “treatment” as long as it’s a pill you can take, a brain fix-all. This convenience culture idea of the quick fix is what has lived on, and now psychiatric “treatment” consists primarily of trying various drugs on patients, having them report the way the drugs affected them, and then trying other drugs. Repeat ad infinitum. This guinea pig approach to psychiatry is what I have witnessed for many years, and with a variety of different psychiatrists. They no longer seek out the underlying traumas of patients, as in the old quaint days. It is all about the drugs today, and nothing else is even discussed.
Psychiatrists are corporate America’s drug pushers.
Banning Guns For Citizens?
Now I’m going to get a lot of hostile responses for bucking the knee-jerk hysteria about banning assault rifles that’s going around. It seems to me like this issue was custom-tailored to distract the nation from the “fiscal cliff” backroom betrayals currently gutting your Social Security and Medicare inside the centers of power. There are numerous massacres, unfortunately. The media volume generated by this particular one is like a tsunami and changes the top story away from the machinations of the White House and Congress, where their long-planned deal-making could potentially kill many, many more people than the occasional shooting spree. They actually do kill many, many more children in Afghanistan, Pakistan, Yemen and elsewhere… but that’s a different article.
I see no problem clamping down on high-capacity assault rifles. But I don’t for a second believe that’s going to change anything. What exactly can you do with an assault rifle, that you can’t do with a thousand other different kinds of guns? Reloading isn’t really that time-consuming or difficult. Multiple weapons are easy to obtain, especially if one is motivated enough and doesn’t care if they make it out alive. So how does that solve the problem?
Similarly, the “background checks” don’t catch spree shooters who don’t have criminal records and just one day snap. There’s nothing to check, and future-crime has not been wiped out yet.
Ah, the nuclear option – ban all the guns. That’s next.
There’s an interesting idea. With 300,000,000 guns in America, it should be no problem to just collect them all. Criminals would be first to line up at the weapon depository and rape scan center. Once the criminals are disarmed, things will go smoothly.
Some suggest that the population doesn’t need to be armed, as an armed rebellion against a tyrannical regime is futile. That’s a selective reading of history (and of the Bill of Rights), but even granted it was true, weapons are useful for self-defense from whomever. They can be indispensable in times of chaos or collapse. We do retain the right to defend ourselves, but apparently a lot of liberal/left types would make that technically impossible, by forcibly disarming everyone who complies.
Oh, no doubt, you could be re-armed by enlisting in some civilian human-drone force, as Obama first proposed back in 2008. Selective service in some organized policing force or military unit in order to graduate from high school was a wet dream proposal of the current president’s. There explains the “450 million rounds of 40 caliber” hollow-point ammunition that the Department of Homeland Security just ordered. Perhaps forced teenage DHS police labor can replace professional local police forces, which can be laid off in order to enact even more budget cuts around the nation. There’s a great idea.
But guns are here to stay. They aren’t going anywhere. America is an “armed madhouse” as Greg Palast phrased it, so perhaps it’s time to take a closer look at the “mad” part of the equation.
The year 1999 was a good one for the drug company Merck. In its 64 page annual report, it predicted that the arthritis medicine Vioxx (“Our Biggest, Fastest, and Best Launch Ever!”) would also prevent Alzheimer’s disease and colon cancer. It announced it was seeking approval to market the asthma drug Singulair to two-year-olds. And it forecast that 40 million women would take its new osteoporosis drug, Fosamax, as Merck continued to “help educate both doctors and patients” about the bone disease.
It turned out Merck spoke too soon. Vioxx was withdrawn in 2004 for doubling stroke and heart attacks in long-term users; Singulair now carries FDA warnings about “neuropsychiatric events” and Fosamax is suspected of doubling the risk of esophageal cancer, causing bone fractures instead of preventing them and causing heart problems, intractable pain and jawbone death. Oops!
There’s plenty of ka-ching in selling “strong bones” products for the same reason there was plenty of ka-ching in selling “hormone replacement” products: one-half the population is female, and no one wants to look old. Of course, “avoiding hot ﬂashes” really means “still looking hot” in hormone marketing terminology, and “avoiding fractures” really means “still looking hot” in bone product marketing lingo. That’s why attractive women like Meredith Vieira from the Today show and former Charlie’s Angel Cheryl Ladd and actress Sally Field push bone drugs, just as model Lauren Hutton pushed hormone replacement therapy.
To cash in on Fosamax, the first in the bisphosphonate bone drug class, Merck decided to market the dangers of osteoporosis “far beyond ailing old ladies.” It hired researcher Jeremy Allen to whip up fears of “osteopenia,” the risk of osteoporosis, as a health epidemic to sell bone drugs and planted bone scan machines in medical offices across the country, says National Public Radio. Allen created the faux “Bone Measurement Institute” which also maneuvered Medicare reimbursement for the scans. By 1999, there were 10,000 bone scan machines in medical offices, said the Associated Press, when there had been only 750 before Fosamax.
Like its trouble-laden drug Vioxx, Merck’s Fosamax ﬂew out of the FDA. It received only a six month review before its 1995 FDA approval. (The government also helped its promotion with the HHS secretary herself, Donna Shalala, participating in a 1998 rally kicking off free bone density screenings to be offered in 100 cities.)
But the wheels soon came ﬂying off the bone drug. Patients experienced esophageal “irritation” and the warning to stay upright for one full hour after taking Fosamax, eating or drinking nothing was added after approval. One woman who took Fosamax but remained upright for only 30 minutes, not 60, had to be admitted to the Mayo Clinic with “severe ulcerative esophagitis affecting the entire length of the esophagus” and had to be fed intravenously, according to the New England Journal of Medicine.
Next, dentists and oral surgeons discovered after simple tooth extractions and other in-ofﬁce dental work, the jawbone tissue of patients on bisphosphonates would sometimes not heal but become necrotic and die — a condition called osteonecrosis of the jaw(ONJ), The necrotic condition did not take long to manifest “even short-term oral use of alendronate [Fosamax] led to ONJ in a subset of patients” — wrote a dental journal, but it somehow slipped through Fosamax’s two, three-year clinical trials on which its FDA approval was based. Doctors, dentists, and pharmacists were enraged at what looked like deliberate obfuscation by Merck.
And there were second, third and fourth opinions about Fosamax! According to an FDA epidemiologist writing in New England Journal of Medicine in 2009 there were 23 incidences of Fosamax-associated esophageal cancer in the US and eight deaths and 27 incidences of cancer in Europe and Japan and six deaths.
Next reports in medical journals linked bisphosphonates to the risk of developing atrial ﬁbrillation, or a chronically irregular heartbeat and to severe bone, joint or muscle pain. “In the most serious cases, the pain was so severe that patients could not continue their normal activities,” wrote the FDA in a press release. “Some patients have complete relief of symptoms after they stop taking the drug, while others have reported slow or incomplete resolution.” Clearly, the FDA was trying hard to avoid the word irreversible.
Finally, in a development that suggests tremendous medical ineptitude if not duplicity, bisphosphonates were found to sometimes cause the very fractures they were supposed to prevent. The thigh bones of patients on bisphosphonates have “simply snapped while they were walking or standing,” after “weeks or months of unexplained aching,” reported the New York Times in an article called “Drugs to Build Bones May Weaken Them.”
It should be embarrassing to the medical establishment that a prominent drug company and the FDA “discovered” severe side effects after years of patient use and that bone scans are still merchandised though they are of no value to 90 percent of women, according to the New England Journal of Medicine. It should be further embarrassing that Merck was allowed to make $3 billion a year off a drug that many say would not have been approved had clinical trials lasted longer. Its patent expired in 2008.
Now Merck is about to launch a new drug for osteoporosis called odanacatib which has already intrigued the money men on Wall Street. “Odanacatib may be a viable alternative for patients who need continued therapy and who want benefits beyond what they received from bisphosphonates,” a senior Merck research executive told Reuters without a hint of irony.
Martha Rosenberg is a columnist/cartoonist who writes about public health. Her first book, titled Born with a Junk Food Deficiency: How Flaks, Quacks and Hacks Pimp the Public Health, has just been released by Prometheus Books. She can be reached at: email@example.com.
- New Study Links Fosamax to Esophageal Cancer (prweb.com)
- New Study Links Fosamax to Vision Problems Risk (prweb.com)
- Intramedullary Nailing Surgery Is Successful Treatment For Patients With Femur Fractures From Use Of Fosamax Or Other Bisphosphonates (drug-injury.com)
- Alendronate Oral May Posses Bad Side Effects (businesslawdaily.net)