Regulatory Focus™ > News Articles > FDA Withdraws Approval for Impax's Budeprion after Bioequivalence Concerns Raised

FDA Withdraws Approval for Impax's Budeprion after Bioequivalence Concerns Raised

Posted 15 March 2013 | By

The US Food and Drug Administration (FDA) announced today that it is formally withdrawing the approval of Impax Laboratory's Buproprion Hydrochloride extended release 300mg tablets (Budeprion XL 300 mg), months after asking the company to withdraw the drug after it raised serious concerns regarding the bioequivalence of the generic drug relative to its reference listed drug (RLD).


In September 2012, FDA announced that it had asked Israel-based manufacturer Teva Pharmaceuticals to stop distributing Budeprion XL 300 mg after it conducted testing and found that significant differences existed between Budeprion and Welbutrin XL 300 mg, its RLD. Teva marketed Budeprion, on behalf of Impax, which owned its application and manufactured the drug.

Though a similar review in 2007 had found the drugs existed within acceptable tolerances of one another, a 2012 review by FDA found the opposite. "Budeprion XL 300 mg fails to demonstrate therapeutic equivalence to Wellbutrin XL 300 mg," wrote in its findings.

One of the most basic problems may have come from how the drug underwent bioequivalence testing. FDA said the product was approved at the 300 mg dose based on studies conducted using the 150 mg dose. "This methodology was based on FDA's guidance at the time the products were approved," explained FDA. The agency also noted the lower dose was used as the basis of approval due to concerns that the higher dosage could cause seizures in otherwise healthy adults, and this concern caused FDA to grant Teva/Impax a waiver for the studies-a process it refers to as "waiving up."

At the time of FDA's October 2012 announcement, the agency said it had asked four other manufacturers-Anchen, Actavis, Watson and Mylan-to conduct similar bioequivalency testing on their drugs. The statuses of those reviews are not known at this time.

A Withdrawn Drug

FDA's 15 March 2013 Federal Register notice explains Impax agreed on 30 September 2013 to its request to stop marketing the drug, and noted that the company waived its opportunity for a hearing, thereby expediting the process.

The Federal Register notice marks the formal removal of the drug from the market.

Distribution of the 300 mg version of the drug, approved under Abbreviated New Drug Application (ANDA) number 77-415, is now illegal. The drug still exists under an approved 150 mg formulation.

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