Stamped May 25 1995
NDA 20-358
Burroughs Wellcome Company
Attention: Donald A. Knight
Vice President, Drug Regulatory Affairs
3030 Cornwallis Road
Research Triangle Park, North Carolina 27709
Dear Mr. Knight:
Please refer to your resubmitted New Drug Application
(NDA) dated and received February 28, 1994, submitted pursuant to section
505(b) of the Federal Food, Drug and Cosmetic Act for Wellbutrin® (Bupropion
Hydrochloride) 50, 100, and 150 mg Sustained Release Tablets, NDA 20-358, for
the treatment of depression.
We also acknowledge receipt of your additional
communications (see Enclosure 1).
We have completed our review of your application, and it is not approvable. Under section 505(d) of the Act and 21 CFR
314.125(b)(5) of the FDA implementating regulations, you have failed to provide
substantial evidence consisting of adequate and well-controlled studies, as
defined in 21 CFR 314.126, that Wellbutrin SR® will have the effect it is
represented to have under the conditions of use prescribed, recommended, or
suggested in the proposed labeling.
Please note that we have additionally included a list of environmental
assessment and chemistry and manufacturing concerns to convey all of the
deficiencies in this application.
Overview of Basis for Non-Approvable Decision
Before providing a detailed explanation for our
views on why your clinical program failed to support the antidepressant
effectiveness of Wellbutrin SR in the dose range proposed, we felt it would be
useful to briefly summarize our views on what the critical issues are for this
NDA and to give our historical perspective on how these issues unfolded.
In your December 23, 1994 letter, you acknowledged
that your primary motivation for the Wellbutrin SR program was to develop a
formulation that would be safer with regard to the risk of seizures than the
immediate release (IR) formulation. You
hypothesized that seizure risk was linked to peak plasma levels, and on this
basis, you sought to develop a formulation that would decrease the peak plasma
level and the peak to trough fluctuation for bupropion and its metabolites,
while maintaining an equivalent extent of absorption. Although it is true that you obtained FDA’s general prior
agreement that a bioequivalence approach as outlined above would suffice, along
with adequate safety data for the new formulation, it was not apparent at that
time that you also sought to substantially change the recommended dosing range for
this drug.
Back a Page
Next Page
Back to Wellbutrin SR® NDA Index Page
Back to Main
Index