Bioequivalence and Bioavailability Forum

Hi all,

Last night I was doing some reading on the FDA Wellbutrin XL BE issues. Briefly, Teva's generic was approved based on showing BE to WXL at 150mg strength. 300mg strength is not a RLD due to safety reasons. Therefore their 300mg strength filing was based in-vitro dissolution (and proportional composition). From the FDA article¹, results from teva's study were:

Fasting Cmax Ratio=89% (CI 80.3%–98.2%); AUC Ratio=98% (CI 91.9-104.4%)
Fed Cmax Ratio=110% (CI 103.2%-118.4%); AUC Ratio=108% (CI 101.4-115.4%)

Since the fasting Cmax barely passed with a lower CI limit of 80.3%, shouldn't this have raised a red flag with regards to Teva's 300mg filing via in-vitro data(f2) + composition proportionality since the target clinical dose is 300mg? Even with f2 >> 50(I don't know if the data was published), there is still a concern since we are dealing with modified release.

The mean Tmax is about 2-3 hours earlier than WXL but then Tmax difference is not in FDA's interest (okay, in general).


John

---
1. Review of Therapeutic Equivalence Generic Bupropion XL 300 mg and Wellbutrin XL 300 mg, Food and Drug Administration, 10/03/12

---

Edit: For some background informations and linked documents see this thread. [Helmut]