The first sessions this afternoon at the AAPS Meeting focus on bupropion, otherwise known, in its branded form, as Wellbutrin. With the introduction three years ago of a generic for the antidepressant, patient switched to generic bupropion began to complain that the new drug was not working as well as the branded version had. They reported reduced control of their depression or even suicidal symptoms.
Theoretically at least, the two drugs were the same for all intents and purposes. The FDA had evaluated the data on the generic before approving it and certified that the branded and generic drugs were bioequivalent.
Yet, patients were reporting in increasing numbers, particularly online via patient advocacy sites, that this was not so. Now drugwonks and the Center for Medicine in the Public Interest are both on the record discussing why the internet is not a reliable source of data on medical information, and calculating prevalence of side effects is no exception to this.
However, the internet was not the only place that complaints were accumulating about generic bupropion. And an in vitro study done by one of the sites receiving these complaints revealed that 34 percent of the contents of the generic was being released in the initial two hours. That percentage was only 8 percent for the branded drug. Despite concerns about the bioequivalence of the two versions, the FDA reiterated that the two were the same.
Since then, this line has been maintained. One of this afternoon’s speakers, Dr. Paul Fackler, Vice President of Biopharmaceutics in Global Generic R&D at Teva Pharmaceutical, one of the companies making the drug and the first to produce a generic of bupropion, argued that the data does show that the release pattern of the drugs is indeed very similar.
There is one obvious source of doubt of this, despite Dr. Fackler’s lovely graphs, is that they are simulations, not creations of actual data. The argument for this is that only so much blood can be drawn from volunteer subjects so producing a full graph over the drug’s 20 hour half life is unfeasible. Yet, the simple fact that they are simulations leaves the numbers very open to questions.
The second issue, and one that has existed since the beginning of the controversy over the bioequivalence of branded and generic bupropion, is that the FDA tested only the 150mg dose, not the 300mg dose. As Dr. Fackler explained this afternoon, an in vivo waiver was granted on 300mg. With the larger dose being the target of many of the reports of therapeutic inequivalence, it seems short sighted of the FDA not have asked for data on 300mg after complaints began to stream in, if not during approval.
