FDA higher-ups pushed forward with a controversial rule that makes it harder for patients to learn of drugs' side effects despite objections from its own experts, a new report shows. The rule also removes patients' ability to sue pharmaceutical manufacturers when harmed by a drug.

In 2006, FDA changed its policy for updating drug labels. Drug makers must now seek FDA approval before adding new information to labels, even if that information is critically important to public health. Critics say the mandatory FDA approval is inefficient and that FDA does not have the resources to act quickly on all label-change requests.

The rule also reversed the agency's longstanding position on preemption of common law, according to the new report, released by House Oversight and Government Reform Committee Chairman Henry Waxman (D-CA). If FDA approves a drug and its label, drug makers are shielded from liability, removing the right of citizens harmed by a drug to seek legal redress. From the report:

FDA has historically viewed state lawsuits as providing a valuable complement to the agency's regulation of these products.3 The agency has asserted that these cases help to uncover risks that are unknown to the agency at the time of approval and that they provide an important additional layer of consumer protection against unsafe products.

The two issues (label-change approval and preemption) are interrelated. By mandating FDA approve changes to drug labels, the agency provides drug makers even more protection from citizen suits. Since the rule preempts common law, FDA approval shields drug makers from so-called "failure-to-warn" claims.

The Waxman report shows that experts inside the FDA opposed both controversial aspects of the rule. Dr. John Jenkins, who works in FDA's drug review office, said, "We know that many current approved drug labels are out of date and in many cases contain incorrect information (e.g., the overdose section) … [I]t is unwise to suggest that FDA approved labeling is always up-to-date and always contains a full and complete listing of all pertinent risk information."

Like many others at FDA, officials from research centers inside the FDA objected to preemption of common law:

[T]he centers believe that an extensive discussion of preemption should not be included in this rule. The question of preemption is tangential to the purpose of this rule and any controversy that results from including it in the final rule may detract from the public health benefits that will be realized from revising prescription drug labeling.

The White House could have been responsible for including preemption in the rule, known as the Physician's Labeling Rule. Waxman's report says Bush administration officials have not turned over all documents related to FDA's communications with the White House. "The documents that have been provided, however, suggest that officials in the White House and the Department threatened to block the Physician Labeling Rule, a major public health initiative on which FDA career officials had worked for many years, until the preemption changes were included," the report says.

FDA's rule is bad for consumers and is a prime example of the Bush administration's penchant for making sure regulated industries are subject to as little government and legal oversight as possible. In Waxman's report, Jane Axelrad, Associate Director for Policy in the Center for Drug Evaluation and Research, sums it up best: "The rule is not, as it purports to be, consistent with the agency's role in protecting the public health."

FDA's panel of independent science advisors charged with reviewing the agency's work on bisphenol-A, a chemical commonly found in hard plastics and the lining of food cans, criticized FDA's current policy on the substance. The panel has "significant concerns" with the draft scientific assessment FDA released in August.

In FDA's draft assessment, the agency identified "margins of safety" for both infants and adults and contended, at levels most humans are exposed to, the margins are adequate. But the science panel's report says the available evidence "provides a sufficient scientific basis to conclude that the Margins of Safety defined by FDA as 'adequate' are, in fact, inadequate."

The panel criticized the agency's selection of studies on which it based its assessment, saying FDA excluded many studies suitable for determining the health effects of exposure to bisphenol-A. The report says FDA's list of the studies it used "creates a false sense of security about the information that is used in the assessment, however, as it overlooks a wide range of potentially-serious findings."

Last week, a Milwaukee Journal Sentinel investigation turned up evidence showing FDA used studies funded by the plastics industry lobby and some studies that are decades old.

The panel's stinging rebuke of FDA's risk assessment will quiet charges that the panel chair, Martin Philbert, has unacceptable ties to an anti-regulatory activist, Charles Gelman, who believes bisphenol-A is perfectly safe. The tone of the report and the panel's recommendation that FDA look at more studies finding bisphenol-A poses a risk vindicate Philbert who claims he was aware of Gelman's views but would not be swayed by them.

FDA continues to bury its head in the sand. In a press release responding to the panel's report, FDA says, "Consumers should know that, based on all available evidence, the present consensus among regulatory agencies in the United States, Canada, Europe, and Japan is that current levels of exposure to BPA through food packaging do not pose an immediate health risk to the general population, including infants and babies."

Nearly every study on bisphenol-A raises concerns. A recent study published in the Journal of the American Medical Association concludes human adults with high levels of bisphenol-A in their urine are at greater risk of heart disease and diabetes. The National Toxicology Program — which, like FDA, is an arm of the U.S. Department of Health and Human Services — "has some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures."

By now, most are aware that the Food and Drug Administration continues to assert that bisphenol-A, a chemical commonly found in plastics and food containers, is safe for humans despite the mountain of independent studies that say otherwise.

The Milwaukee Journal Sentinel continues to shed light on how and why FDA is able to maintain claims of safety. The FDA staff report on bisphenol-A safety is based on research sponsored by the plastics industry:

The newspaper reviewed the body of evidence that the task force considered. It found memos with entire sections blacked out, reviews commissioned by the American Plastics Council, an arm of the American Chemistry Council, and reviews completed by consulting firms with clients who have financial interests in the sale of bisphenol A. …

Much of the science that the task force considered was 20 years old or older, including a study commissioned in 1976.

A panel of independent experts is reviewing the FDA staff report and is expected to give its opinion later this month.

The panel will have the opportunity to expose the incredible flaws in FDA's research. However, as Reg•Watch blogged last week, the FDA-appointed chair of the panel has ties to an anti-regulatory zealot who is also convinced of bisphenol-A's safety.

Scientists cannot say with 100 percent certainty how bisphenol-A affects the body or what doses of the chemical are dangerous. However, nearly every study on bisphenol-A raises concerns. A recent study published in the Journal of the American Medical Association concludes human adults with high levels of bisphenol-A in their urine are at greater risk of heart disease and diabetes. The National Toxicology Program — which, like FDA, is an arm of the U.S. Department of Health and Human Services — "has some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures."

Considering studies like those, FDA should provide at least some protection from bisphenol-A while gaps in the scientific literature are closed. Setting an exposure standard is essential to both human health and peace of mind.

This morning Reg•Watch blogged about EPA's revision to the national air quality standard for lead. The new regulation is significantly better than the current standard which had not been revised since 1978.

But another part of the new regulation raised Reg•Watch's suspicion. Currently, the network EPA uses to monitor concentrations of airborne lead has some serious problems. According to Felicity Barringer at The New York Times, "Currently, 133 monitors are in operation nationwide, down from about 800 in 1980, an E.P.A. spokeswoman, Cathy Milbourn, said."

That's a problem because, after all, you can't enforce an air quality regulation if you don't know how much pollution is in the air. Recognizing this, EPA proposed some new requirements for monitoring lead particles suspended in the air.

In its proposed rule, released in May, EPA announced that it would set emissions thresholds as one criterion to determine whether monitoring is needed. The air around any facility emitting amounts of lead above the threshold would have to be monitored. EPA proposed a range for the threshold: 200 kg - 600 kg per year.

A draft of the final rule circulating among officials at EPA and OMB just days ago showed that EPA had settled on ½ ton per year as the final threshold. But the final rule, published yesterday, set the emissions threshold at 1 ton per year. What gives?

Well, the White House Office of Management and Budget may be responsible for the decision to water down the emissions threshold requirement. On Oct. 14, just one day before EPA administrator Stephen Johnson signed the final version of the rule, an EPA employee sent an email to an OMB employee saying, "[I]f OMB wants a 1 ton threshold, it would have to provide a rationale for that point of view."

The officials named in the email are the same who squared off during EPA's recent revision to the national standard for ozone, or smog: EPA deputy administrator Marcus Peacock and Susan Dudley, head of OMB's Office of Information and Regulatory Affairs.

Apparently, OMB was able to provide some kind of rationale that satisfied EPA. According to EPA estimates, the ½ ton threshold would have swept in about 259 lead polluting facilities while the 1 ton threshold will apply to 135 facilities. Reg•Watch is not well versed in air quality monitoring, but something sure smells fishy. Feel free to email with thoughts or insight.

Yesterday, the Environmental Protection Agency announced a new national air quality standard for lead which will lead to cleaner air and healthier children. EPA tightened the standard to 0.15 μg/m³ from the current level of 1.5 μg/m³. The standard has not been revised since it was first set in 1978.

The new standard is consistent with the advice of EPA staff and its scientific advisors who had called for a standard between 0.10 μg/m³ and 0.20 μg/m³.

Removing lead from gasoline went a long way in improving public health, but lead still poses a threat. It persists in the environment like the dickens. Lead can be especially dangerous for kids. According to EPA, lead exposure can affect brain development and "can lead to IQ loss, poor academic achievement, permanent learning disabilities, and delinquent behavior." Many environmentalists and children's health advocates are hailing EPA's decision.

For now, it looks as though EPA set the standard absent from any undue political influence. (The White House, perhaps acting on behalf of industry lobbyists, meddled with EPA's recently revised ozone standard.) Industry lobbyists were asking EPA to leave the lead standard alone or choose a much weaker option, but EPA resisted.

However, we cannot totally discount the prospects of White House or industry interference. One shortcoming of the rule concerns how compliance is determined. Currently, EPA looks at the concentration of lead in air everyday and averages those figures over a three-month period. If an area's average is more than the standard, the area is out of compliance. If the average is under the standard, everything is hunky dory.

EPA's science advisors want the agency to change this formula to calculate the average over a one-month period. This would better account for big spikes in emissions. In the current compliance system, two months of low emissions could attenuate emissions spikes in the third month. Subsequently, polluters may have an incentive to release lead emissions in bursts.

EPA's advisors say switching to a one-month averaging time would be more protective of those most sensitive to lead's effects (like children) who can be hurt by higher, albeit shorter, exposures. Irrespective of the level of the standard, shortening the averaging time effectively makes for a stricter regulation.

But EPA chose to continue averaging airborne lead concentrations over a three-month period. In a meeting with the battery recycling lobby, whose clients will face compliance with the stricter standards, a product defense firm gave White House officials a slide-show attacking the science EPA used as the basis for the new lead regulation. In the document, the firm attempts to undermine the scientific evidence that short-term exposures can be harmful. The firm even goes so far as to say, "A 1 month exposure will increase blood lead, but blood lead will decrease after the exposure ceases."

Was the product defense firm specifically lobbying the White House against a one-month averaging time? Did White House officials pressure EPA to adopt that view? We may never know. But we do know that continuing the three-month averaging time is not consistent with the advice of EPA's science advisors and is not as protective of public health as it could be.

Reg•Watch Update: "Did OMB Weaken EPA Efforts to Monitor Airborne Lead?"

Over the weekend, the Milwaukee Journal-Sentinel broke the news that the head of an FDA advisory panel studying the safety of the chemical bisphenol-A (BPA) has ties to an "anti-regulation activist" who happens to think BPA is perfectly safe.

The activist and retiree from the manufacturing industry, Charles Gelman, was "once labeled the second worst polluter in Michigan by the state's Department of Natural Resources," according to the Journal-Sentinel. Gelman donated $5 million to the University of Michigan Risk Science Center which is headed by Martin Philbert. Philbert is also the chair of the FDA Science Board's subcommittee on BPA.

That committee is preparing to release its opinion on the safety of BPA, a chemical used in hard plastics and in the lining of food cans. The committee's recommendation could affect FDA's decision to limit BPA in consumer products or its decision not to regulate at all.

Currently, FDA says BPA is safe at levels to which humans are exposed. But that opinion has been marred by its own controversy. FDA is relying on two flawed studies, according to the House Energy and Commerce Committee: [I]t appears that the Food and Drug Administration's position on BPA's safety is entirely dependent on two studies, both of which are funded by the American Plastics Council, and one of which has not been published or peer-reviewed."

The lion's share of scientific literature would move FDA toward a finding that BPA is not safe, according to The Washington Post: "From 1997 to 2005, 116 studies of the compound were published. Of those funded by government, 90 percent showed evidence of a health effect linked to BPA."

But even after JAMA published a new study finding evidence of harm in humans exposed to BPA (which was first presented in front of Philbert's committee), FDA officials continue to tell the public BPA is perfectly safe.

Philbert says Gelman has not, and will not, affect his decisionmaking. Gelman says he has told Philbert on multiple occasions that he believes BPA is safe. Philbert denies he and Gelman spoke on the matter.

He-said-he-saids are tough to settle, but the circumstantial evidence doesn't look good: Gelman made the contribution either shortly before or shortly after Philbert was named committee chair, according to the Journal-Sentinel.

Public health advocates had hoped the advisory panel's recommendation would provide clear cut advice that FDA would be pressured to follow. Three recent studies have raised additional flags about BPA's safety. Unfortunately, regardless of whether Philbert's judgment is colored, the panel's credibility is suffering.

FDA should have done a better job of weeding out this potential conflict. Philbert did not declare the donation when filing the requisite conflict-of-interest disclosure information, but FDA's response to the new scandal is just as pitiful as its vetting of him. From the Journal-Sentinel:

Norris Alderson, the FDA's associate commissioner of science, learned of the link from the Journal Sentinel. He looked into the matter and said he was satisfied there was no conflict of interest because Philbert's salary is not paid by the donation.

Considering Philbert is a founder and co-director of the now-flush-with-cash Risk Science Center, Alderson's claim is ridiculous.

The Government Accountability Office (GAO) has released a new report describing how the Food and Drug Administration handles conflicts of interest on its advisory panels. Financial conflicts plague a significant number of FDA advisors and FDA panels, according to the report.

FDA advisory committees can provide valuable advice to decisionmakers inside the agency "particularly concerning controversial issues or new products," according to GAO. Committees can weigh in on the safety and efficacy of a pharmaceutical awaiting approval or the safety of chemicals found in every day products — as FDA's science board did in September when it considered the safety of bisphenol-A. "The advisory committees' recommendations are not binding on the agency, but the agency usually follows the advisory committees' advice," GAO says.

But committee members, or potential members, sometimes have financial conflicts (such as owning stock in a company with a product before the committee) that call into question their ability to provide unbiased input. In those cases, FDA can provide a waiver if it believes a person's service is critical to the operation of an advisory panel.

FDA is not doing a good job of filling panels with impartial experts and issuing too may waivers. GAO examined a sample of advisory committee meetings and made these key discoveries:

• At least one member on 49 of the 83 meetings examined had a conflict;
• Two hundred of the 1,218 participants had a conflict — about 16 percent;

FDA officials acknowledge that their source for expertise is the same as industry's:

FDA contended that it sought the same leading experts to serve on its advisory committees as industry sought to conduct its research and product trials. As a result, the experts FDA deemed most qualified to serve on its advisory committees often had industry ties, according to the agency.

GAO says that FDA needs to improve its efforts to recruit committee members. FDA's primary vehicle for recruitment is word-of-mouth which means committee members tend to be those experts known to agency officials or to an industry with a product under review. "[I]t may lead to self-perpetuating committee membership, in which a limited group of peers continually comprise an advisory committee."

The report is available here: FDA Advisory Committees: Process for Recruiting Members and Evaluating Potential Conflicts of Interest

EPA is finalizing a potentially major revision to the national air quality standard for lead, and industry has come a knockin'. On Oct. 2, several officials from the Office of Management and Budget's Office of Information and Regulatory Affairs (OIRA) — the arm of the White House in charge of reviewing and editing new rules — met with several lobbyists from the battery recycling industry. That industry would eventually face new compliance requirements if EPA adopts a strict new standard.

One official from the White House Council of Economic Advisors, one from the White House Council on Environmental Quality, one official from EPA, and another from the Department of Energy also attended.

In May, EPA proposed tightening the standard for lead exposure to between 0.10 μg/m³ (micrograms per cubic meter) and 0.30 μg/m³. The current standard, which EPA has not revised since 1978, is 1.5 μg/m³.

At the meeting, the Gradient Corporation — a product defense firm whose clientele has included the tobacco industry — circulated a 15-page slide show reviewing the scientific uncertainty surrounding EPA's proposal. Injecting uncertainty into regulatory science is a common tactic of product defense firms and industry lobbyists. (Public health expert David Michaels profiled this extensively in his book Doubt is Their Product.)

The slide show is a veritable how-to manual for White House officials who like to challenge the conclusions of agency scientists in order to undermine environmental and public health regulations. (See the right whale rule for a recent example.)

Lobbyists at the meeting also complained of the potential compliance costs the rule would impose. In comments on the proposal, the Association of Battery Recyclers said a tighter standard "will threaten the continuing viability of the industry."

Fortunately for the public, the Clean Air Act prohibits EPA from considering economic factors when it sets major air quality standards. EPA must base its determination on health issues.

Lead exposure poses a number of health risks for humans, especially kids. According to EPA, lead exposure can affect brain development and "can lead to IQ loss, poor academic achievement, permanent learning disabilities, and delinquent behavior." Lead exposure can also damage red blood cells and weaken a child's immune system.

But that won't stop industry lobbyists from pressuring federal officials to finalize a rule weaker than what was proposed in May. And White House officials, never shy to circumvent the law, may help those industry lobbyists pressure EPA. The mere presence of an official from the White House Council of Economic Advisors is cause for concern. If EPA cannot consider economics, what value can economic advisors possibly add to the discussion?

The whole scenario is similar to the events leading up to EPA's revision to the national air quality standard for ozone, or smog. During that rulemaking, EPA proposed a range from which it would choose a final standard. When making its decision, EPA faced pressure from industry lobbyists and interference from White House officials.

If the pattern follows, EPA will ultimately take a step in the right direction but fall short of fully protecting public health. EPA tightened the standard for ozone but chose the upper end of its proposed range. EPA's staff scientists and independent advisors, as well as environmentalists and public health advocates, all agree the upper end of the proposed range for the lead standard, 0.30 μg/m³, is inadequate to fully protect human health.

EPA is under court order to finalize the rule by October 15. Stay tuned to Reg•Watch for updates.

As expected, the Environmental Protection Agency will not limit perchlorate in public drinking water supplies. Perchlorate is a chemical used in rocket and jet fuel and is a known inhibitor of human thyroid function. Because of its widespread use, perchlorate has made its way into drinking water systems across the nation.

EPA says that perchlorate is not present at high enough levels to cause adverse health effects in more than 99 percent of drinking water systems. Therefore, a limit on perchlorate is unnecessary.

EPA made the announcement on Friday afternoon when the federal government usually dumps information it doesn't want people to pay attention to. Juliet Eilperin at The Washington Post told the tale on Saturday:

Last month, The Washington Post reported that White House officials had extensively edited the EPA's perchlorate rule-making documentation to remove scientific data highlighting some of the risks associated with the chemical, which has been found in water in 35 states. The Defense Department and Pentagon contractors who face legal liability stemming from rocket fuel contamination have lobbied for six years to avoid a federal drinking-water standard for perchlorate.

In the document released yesterday, the EPA assumes that the maximum safe perchlorate contamination level is 15 times higher than what the agency suggested in 2002.

By that standard, the EPA estimates that more than 16 million Americans are exposed to the chemical at a level that is unsafe.

EPA will accept public comment on the rule once it is published in the Federal Register.