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2021 FDA Science Forum

Current Knowledge Gaps and Regulatory Challenges in the Evaluation of Biowaivers for Biopharmaceutical Classification System (BCS) Class III- “like” Drugs

Download the Poster (PDF; 0.29 MB)
Authors:
Poster Author(s)
Chimalakonda, Krishna, FDA/CDER; Taur, Jan-Shiang , FDA/CDER; Zhao, Chunsheng, FDA/CDER; Darna, Mahesh, FDA/CDER; Chaluvadi, Madhusudana, FDA/CDER; Cai, Wendy, FDA/CDER; Ren, Ke, FDA/CDER; Braddy, April, FDA/CDER;
Center:
Contributing Office
Center for Drug Evaluation and Research

Abstract

Poster Abstract

BACKGROUND

The current FDA guidance recommends that for a waiver of in vivo bioequivalence (BE) study to be justified, a Biopharmaceutical Classification System (BCS) class III test product must contain qualitatively (Q1) the same and quantitatively (Q2) very similar excipients when compared to the reference listed drug (RLD), and, the drug product dissolution must meet the “very rapidly dissolving” criteria. There has been minimal regulatory precedence on granting biowaiver for BCS class III drugs.

PURPOSE

The purpose of this project is to study the relationship between formulation Q1/Q2 similarity and in vivo bioequivalence outcome in a group of BCS class III-“like” drugs, as well as to investigate whether the dissolution rate of these products meet the "very rapidly dissolving" criteria

METHODOLOGY

A total of nine BCS class III- “like” drugs were identified from ~70 Abbreviated New Drug Applications (ANDAs). An assessment on the formulation composition and the dissolution data of the test and RLD products were conducted.

RESULTS

The results show that bioequivalence between the test and RLD are demonstrated when critical excipients (i.e., croscarmellose sodium, magnesium stearate, povidone, corn starch and lactose) in the test product are not Q1/Q2 the same/similar to the RLD. Majority of BCS class III- “like” drug products demonstrated >85% drug-release within 15 min.

CONCLUSIONS

The result that bioequivalence is demonstrated for products with excipient differences beyond Q1/Q2 the same/ similar (in conjunction with very rapid dissolution) provides supporting evidence for a possibility for the Agency to re-consider its “Q1/Q2 similarity” criteria set in the current guidance for BCS class III biowaiver. Additional investigation is needed if further guidance advancement is warranted.

Poster Image
Current Knowledge Gaps and Regulatory Challenges in the Evaluation of Biowaivers for Biopharmaceutical Classification System (BCS) Class III- “like” Drugs

Download the Poster (PDF; 0.29 MB)

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