Bioequivalence and Bioavailability Forum

Hi Sameep,

❝ Are permeability studies reported in literature (like absolute bioavailability >85%) acceptable for establishing BCS class I and apply for BCS Biowaiver (ANDA)?

IMHO, studies from trustworthy sources (not published in the “Timbuktu Journal of Clinical Pharmacology”) should suffice. The devil is in the details. Likely those studies were performed by the originator – quite often in just twelve subjects. The guidance (Section B.1.) tells us:

A sufficient number of subjects should be enrolled to provide a reliable estimate of extent of absorption.

(my emphasis)

However, in a recent review* we find:

Permeability/Stability in the GIT
   When the drug is in solution, the in vivo permeation does not depend upon the quality of the API but of the mechanism of permeation and on drug stability. For this reason, the EMA considers published human data as sufficient. The USA will consider published data only in a supportive capacity because the underlying data is not available for review, and thus, it cannot be confirmed that proper methodology was used.

Given that, for an ANDA I would say you have to re-invent the wheel. Good luck manufacturing the IV formulation according to cGMP. Ask the OGD what a “sufficient number of subjects” is.

---

• Cardot J-M, García Arieta A, Paixão P, Taševská I, Davit B. Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches. AAPS J. 2016;18(4):1039–46. doi:10.1208/s12248-016-9915-0.