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Stephanie Sutton was an assistant editor at Pharmaceutical Technology Europe.
Last week, FDA deemed that a generic drug manufactured by Impax Laboratories and marketed by Teva Pharmaceuticals USA was not therapeutically equivalent to its reference product.
Last week, FDA deemed that a generic drug manufactured by Impax Laboratories and marketed by Teva Pharmaceuticals USA was not therapeutically equivalent to its reference product. The drug in question, Budeprion XL 300 mg, was approved in the US in December 2006 as a generic form of GlaxoSmithKline’s antidepressent drug, Wellbutrin XL 300 mg.
Budeprion XL 300 mg (bupropion hydrochloride extended-release tablets) has been under the watch of the US regulator for several years. Between January 1 and June 30, 2007, FDA received 85 postmarketing reports concerning patients who had switched from the branded product to Budeprion XL 300 mg. Specifically, the concern was that there was a reported loss of efficacy following the switch. In 2008, however, FDA announced the results of a review of Budeprion XL 300 mg. The verdict:
“The FDA considers the generic form of bupropion XL 300 mg (Teva Pharmaceuticals) bioequivalent and therapeutically equivalent to (interchangeable with) Wellbutrin XL 300 mg. Although there are small differences in the pharmacokinetic profiles of these two formulations, they are not outside the established boundaries for equivalence nor are they different from other bupropion products known to be effective.”
So why did last week see a change in opinion? The u-turn by FDA follows the results of a new bioequivalence study sponsored by FDA that compared Budeprion XL 300 mg to Wellbutrin XL 300 mg. The results, which became available in August 2012, showed that Budeprion XL 300 mg failed to release the active ingredient into the blood at the same rate and to the same extent as GlaxoSmithKline’s original drug. No other new safety data were identified.
Four other generic-drug alternatives to Wellbutrin XL 300 mg are available on the US market. FDA has not conducted bioequivalence studies with these products, but has asked the manufacturers Anchen, Actavis, Watson and Mylan to conduct their own studies in this regard. Data must be submitted to FDA by March 2013.
FDA does not currently have data indicating that the other generic drugs will also fail to be to be therapeutically equivalent to Wellbutrin XL 300 mg and it is possible that the issue is unique to the Budeprion XL 300 mg. FDA has said it will provide an update when further information is available.
The worrying aspect to this news is that it may affect the reputation of generic drugs as a whole, particularly if the other generic forms of Wellbutrin XL 300 mg are also shown not to be therapeutically equivalent. It would raise questions among both patients and physicians as to how comparable a generic drug really is to its reference product.
Because of the expensive nature of pharmaceutical development, branded medicines always necessitate a high price tag. Generics, on the other hand, are much cheaper and provide huge cost savings for patients and governments. In the US alone, generic drugs were reported to have accounted for cash savings of around $192 billion in 2011.
Let us hope this incident is unique to the Teva/Impax product and does not affect other generic drugs. FDA will also, no doubt, be more cautious. In its statement on Budeprion XL 300 mg the agency added that it is already in the process of revising its guidance to industry about how to conduct premarket bioequivalency studies in generic bupropon products.