By Susan J. Matthees –
FDA recently denied a 2006 citizen petition submitted by Wyeth Consumer Healthcare (“Wyeth”) requesting that FDA withdraw a 2005 Notice of Proposed Rulemaking (“NPRM”) that would reclassify phenylpropanolamine (“PPA”) from Category I (generally recognized as safe and effective) to Category II (not generally recognized as safe and effective). Wyeth alleged that FDA’s proposal to reclassify PPA was based on one flawed study of PPA and that the NPRM incorrectly described the safety status of PPA. FDA disagreed, stating that the weight of evidence indicates that PPA’s safety has not been demonstrated.
PPA has a relatively long history of use in the United States. The ingredient was synthesized in the early 1900s and by the early 1940s was used in OTC nasal decongestant products. Beginning in the 1970s, PPA was marketed as an appetite suppressant in OTC weight control drug products. According to FDA, a 1991 review of adverse event reports from 1977 to 1991 and published studies on PPA suggested that PPA might be associated with an increased risk for hemorrhagic stroke. In 2000, FDA’s Nonprescription Drugs Advisory Committee evaluated data on PPA and concluded that PPA should not be generally recognized as safe. That same year, FDA conducted its own analysis of PPA data and requested that manufacturers voluntarily discontinue marketing products containing PPA. In 2005, FDA proposed the reclassification of the ingredient from Category I to Category II.
Wyeth objected to the proposed reclassification, alleging that FDA based its proposal to reclassify PPA on the findings of one flawed study, the Yale Hemorrhagic Stroke Project (“HSP”). According to Wyeth, the HSP study is not a reliable study because the findings were based on a small number of cases and that there were a number of errors in the study, including errors in determining subject eligibility and classification and confounding factors that could undermine the validity of the results.
FDA disagreed that the HSP study was fatally flawed, saying that Wyeth failed “to present convincing evidence that the HSP study is irreparably compromised.” FDA also explained that the Agency’s proposal to reclassify PPA was based on all available data for the drug and the totality of the evidence suggested that the drug’s safety has not been demonstrated. FDA reviewed 20 years of adverse event reports for PPA and the published results of a Korean study that was similar to the HSP. Although Wyeth had criticized the Korean study, FDA concluded that the study provides “additional supportive evidence.” FDA also stated that the adverse event reports for PPA are consistent with known biological effects of PPA on blood pressure.