NDA
21-515
WELLBUTRIN
XL
Summary
of Clinical Pharmacology and Biopharmaceutics Findings
4.1 Background
WELLBUTRIN XL tablets are bupropion hydrochloride extended release tablets for once daily administration for major depressive disorder. WELLBUTRIN XL tablets (NDA 21-515, August 26, 2002) received an approvable action letter on June 24, 2003, to which the present submission is a complete response.
The Clinical Pharmacology and Biopharmaceutics Recommendations for that submission were that the submitted data were acceptable, pending the outcome of the DSI inspection report of the pivotal bioequivalence study (AK1BIOVAIL2543). Based on the DSI report and further review dated 6/20/03, the study was considered acceptable. The Office of Clinical Pharmacology and Biopharmaceutics (OCPB) recommended the following:
· A change n the in vitro dissolution specification
· A literature review and adverse event review to evaluate the potential for drug interactions with CYP2B6 substrates/inhibitors.
· Specific revisions of the proposed label’s text, including revisions regarding CYP2B6-mediated drug interactions.
The Sponsor has submitted a complete response to the approvable letter. The response to the Clinical Pharmacology and Biopharmaceutics recommendations will be addressed here.
4.2
Current Submission
3.2.1
Dissolution Specifications
·
Is the proposed dissolution specification acceptable?
The Office of Clinical Pharmacology and Biopharmaceutics recommended that the
specification be changed to the following:
2
hours:
4
hours: [blacked out]
8
hours:
16
hours:
This recommendation was based on an approximate 10% deviation from the mean dissolution profiles from bioavailability lots. This reflected the Guidance from Industry “Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations” that states when dissolution specifications are set without an
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