New pregnancy labeling rules should be approved without delay

Aug 2 2007

Marks the tenth anniversary of a public hearing that was hoped to spark substantial changes in the way drugs are labeled for use during pregnancy.

However, 10 years after the FDA recognized that the rules needed to be revamped, they have still not been modified, resulting in anxiety on the part of physicians and patients and the unnecessary termination of wanted pregnancies. A position paper published online in Birth Defects Research Part A, the official journal of The Teratology Society, reviews the history and rationale behind the effort to change pregnancy labeling and calls for the immediate approval of new rules that have been proposed by the FDA. The journal is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/bdr.

Written by the Public Affairs Committee of the Teratology Society, the paper notes that the possibility that medication taken during pregnancy could cause congenital abnormalities became more widely understood in 1961, when birth defects caused by thalidomide started to be recognized. An increase in animal testing and reports of varying quality on birth defects in humans in the 1970s only served to confuse clinicians. The FDA introduced pregnancy labeling categories in 1979 that were meant to make it easier for doctors to determine the safety of prescribing drugs, but Teratology Society members found the categories lacked information about the nature, severity, timing, and treatability of potential fetal damage and overall found them to be unhelpful, according to the paper.

Following a 1992 symposium sponsored by the public affairs committee of The Teratology Society and a position paper published in 1994, the FDA convened a public hearing in 1997 to discuss the content and format of labeling. "With few exceptions, the presentations that day were uniform in identifying the pregnancy categories as a source of inaccurate counseling," the committee states. An FDA summary acknowledged, among other points, that the categories are confusing, are not adequate to communicate risk, create the incorrect impression that drugs within the same category have a similar toxic potential, and do not contain information on possible adverse effects based on severity, incidence, type of effect, dosage, frequency, or gestational timing of exposure.

The 1997 hearing prompted the FDA to revise its pregnancy labeling regulations by replacing the categories with clearer and more complete summaries of information on risk. The FDA has drafted proposed rules that would include information on pregnancy registries, a narrative description of the risks of using the medication, and a discussion of considerations to address inadvertent exposures. Categories would be eliminated, but standardized language would lead to categorization nonetheless, since the likelihood of risk would be categorized as none, low, moderate, high, or unknown. "It remains to be seen whether the criteria for each category are interpreted with sufficient flexibility to result in scientifically sound risk communication," according to the committee, but it maintains that the new system offers important advantages over the old one.

The committee recommends approving the new rules and releasing them for public comment without further delay, since the FDA estimates that the new system will not become effective before 2010, 13 years after the public hearing calling for change. It also recommends applying the categorical language flexibly and including the reasoning behind it. In addition, the committee recommends testing the new system among physicians and consumers to determine whether it is effective at communicating risk and appropriate clinical decision-making. "A mechanism should be developed by which the labeling system can be improved more easily," the recommendations conclude. "The deficiencies of the Pregnancy Categories were recognized by the FDA more than a decade ago, yet at this writing, the Categories are still in place. It should not take so long to fix such a flawed system."

http://www.interscience.wiley.com/journal/bdr