The FDA Flunks

By Sarah Vogel

The Science Board Subcommittee on Food Contact Applications of BPA (Bisphenol A), the expert panel assigned to evaluate the FDA’s Draft Assessment on BPA, released a report Wednesday, October 29, 2008, highlighting a number of severe limitations of the agency’s assessment.  Although judiciously written, the Subcommittee unequivocally gave the agency failing marks on the scientific quality and rigor of its recent assessment.  The Subcommittee’s evaluation of what was by all accounts a poorly prepared report deserves considerable praise and attention.

Without going through the report point-by-point, let’s focus on the two fundamental parts of the safety assessment: the exposure assessment and the criteria used to assess studies of BPA.  

Exposure assessment: grade F
The Subcommittee found the FDA’s exposure assessment to be “severely” limited (p. 13) due to its “lack of consideration of the totality of exposures from other sources”, its limited size, geographical and temporal distribution, and unsupported assumptions about infant feeding and methods of heating formula (p. 5).   The extremely limited data in the exposure assessment provided no insight into the variability of exposure over time within a single individual or across populations.  This problem was further exacerbated by the presentation of the data in mean values with no distributions.  The Subcommittee makes it clear that the FDA needs to completely redo their exposure assessment using updated methods and available data on BPA.

Selection of Toxicological Studies: grade F
In its draft assessment, the FDA chose to largely ignore all of the scientific research on BPA save for two multi-generational studies funded by the chemical industry.  I wrote about this here and contributed to an evaluation of these “Good Laboratory Practice” studies here.  The major chemical trade association, the American Chemistry Council (ACC), declared these studies to be the gold standard of regulatory toxicology and the FDA accepted this position. 

But the Subcommittee came to a very different conclusion.  First, they found that the FDA failed to provide any explanation of the “Redbook 2000” protocols used by the agency and “does not articulate reasonable and appropriate scientific support for the criteria and methods employed in the draft assessment.” (p. 6) The Subcommittee disagreed outright with the FDA’s reliance on the two GLP studies and the agency’s conclusion that the non-GLP studies should be excluded from the evaluation. 

The one exception to the FDA’s failure to include criteria for evaluating studies, which the Subcommittee accurately noted, was when the agency chose to disqualify a given study (p. 6). Although only briefly mentioned by the Subcommittee, this point begs a follow-up question not addressed in their report: was this just another aspect of a poorly conducted report or is this an example of intentional ineptitude at the agency?  The strategy of tearing down unfavorable data to avoid regulation is a well-known tactic of the tobacco and chemical industries.  (Check out David Michaels’ Doubt is Their Product). This is an extremely important point to consider because it raises an important question: can the current FDA conduct a transparent, high quality scientific assessment of BPA? 

The Subcommittee found that those non-GLP studies found to be “adequate” by the Center for the Evaluation of Risks to Human Reproduction should be included in the assessment.  In addition, they concluded that several studies published after the release of the FDA’s assessment needed consideration, including the epidemiological study published by Lang et al. 2008 that found a correlation between urinary BPA levels in adults and coronary heart disease and diabetes[1].   While the Subcommittee noted the limitations of the study, it found that these findings were of concern and “consideration of this study is warranted” (p. 8).   The Subcommittee also mentioned two other studies recently published papers that deserve consideration in the assessment (p. 8)[2]. 

In its final summary, the Subcommittee pin-pointed a key issue to emerge in this debate about BPA:  “the need for application of state-of-the-art risk assessment method…which will enable utilizing all appropriate scientific information available on the potential toxicity of BPA.”  This method should include the use of “academic and government-sponsored studies that are not necessarily GLP-compliant” (p. 13).  This may be the most important conclusion of the report, but what the Subcommittee doesn’t weigh in on is the question that bears repeating: is the FDA capable of such an assessment? 

There is reason to doubt the agency’s abilities. During the question and answer session at the September 16 meeting, one member of the Subcommittee asked the representative from the FDA about their decision to exclude in the assessment a study found to be “adequate” by the CERHR panel.  The response from the FDA official was that while she considered the findings “interesting” there was nothing they could do with them “quantitatively.”  This answer neither inspires confidence nor reflects the level of scientific rigor and leadership we must demand of our regulatory agencies.

The next steps
The charge to the FDA is to determine if BPA is safe.  Safety, according to the agency “means that there is reasonable certainty in the minds of credible scientists that the substance is not harmful under the intended conditions of use.”  The Subcommittee found that the FDA’s safety margin is currently “inadequate” and its assessment poorly conducted.  Determining BPA’s safety is not a matter of needing more scientific research.  There are already over 700 studies on this chemical.  “Credible” minds at the NTP and a consensus of BPA researchers have determined that there are a number of serious risks of exposure to BPA at the levels of human exposure.  The challenge to credible scientists and regulators now is to determine the level and magnitude of the risks presented by current BPA exposure at all developmental stages in life. 

But the challenge presented by this debate over BPA safety extends beyond this one chemical and must be faced by the public, members of Congress and the in-coming Executive Office.   In light of the poor quality of the FDA’s report and serious concerns about the chemical and plastics industry’s involvement in drafting the assessment, can we be assured that the FDA will use the best available science to protect the public’s health?  Or do we need to consider serious reforms at the agency?

 

Sarah Vogel received her PhD from  Columbia University in the Department of Sociomedical Sciences’ Center for the History and Ethics of Public Health and Medicine; her dissertation was entitled “Politics of Plastic: the economic, political and scientific history of bisphenol A.” She holds master’s degrees in public health and environmental management from Yale University. She authored the case study “Battles Over Bisphenol A” at DefendingScience.org.

[1] I. A. Lang et al., “Association of Urinary Bisphenol a Concentration with Medical Disorders and Laboratory Abnormalities in Adults,” JAMA 300, no. 11 (2008).
[2] C. Leranth et al., “Bisphenol a Prevents the Synaptogenic Response to Estradiol in Hippocampus and Prefrontal Cortex of Ovariectomized Nonhuman Primates,” Proc Natl Acad Sci U S A 105, no. 37 (2008), D. C. Dolinoy et al., “Metastable Epialleles, Imprinting, and the Fetal Origins of Adult Diseases,” Pediatr Res 61, no. 5 Pt 2 (2007).