A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs: Evaluation of the Reference-Scaled Approach and Variability Comparison Criterion

被引：48

作者：

Jiang, Wenlei ^{[1
]}

Makhlouf, Fairouz ^{[2
]}

Schuirmann, Donald J. ^{[2
]}

Zhang, Xinyuan ^{[1
]}

Zheng, Nan ^{[1
]}

Conner, Dale ^{[1
]}

Yu, Lawrence X. ^{[3
]}

Lionberger, Robert ^{[1
]}

机构：

[1] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA

[2] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA

[3] US FDA, Off Pharmaceut Qual, Ctr Drug Evaluat & Res, Silver Spring, MD USA

来源：

AAPS JOURNAL | 2015年 / 17卷 / 04期

关键词：

generic drugs; narrow therapeutic index (NTI) drugs; reference-scaled average bioequivalence; within-subject variability; HIGHLY VARIABLE DRUGS; PRODUCTS;

D O I：

10.1208/s12248-015-9753-5

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Various health communities have expressed concerns regarding whether average bioequivalence (BE) limits (80.00-125.00%) for the 90% confidence interval of the test-to-reference geometric mean ratio are sufficient to ensure therapeutic equivalence between a generic narrow therapeutic index (NTI) drug and its reference listed drug (RLD). Simulations were conducted to investigate the impact of different BE approaches for NTI drugs on study power, including (1) direct tightening of average BE limits and (2) a scaled average BE approach where BE limits are tightened based on the RLD's within-subject variability. Addition of a variability comparison (using a one-tailed F test) increased the difficulty for generic NTIs more variable than their corresponding RLDs to demonstrate bioequivalence. Based on these results, the authors evaluate the fully replicated, 2-sequence, 2-treatment, 4-period crossover study design for NTI drugs where the test product demonstrates BE based on a scaled average bioequivalence criterion and a within-subject variability comparison criterion.

引用

页码：891 / 901

页数：11

共 17 条

[1]

[Anonymous], GUID BIOEQ STUD DIFF

[2]

[Anonymous], COMP BIOAV STAND FOR

[3] Determination of Bioequivalence for Drugs with Narrow Therapeutic Index: Reduction of the Regulatory Burden [J].

Endrenyi, Laszlo ;

Tothfalusi, Laszlo .

JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, 2013, 16 (05) :676-682

[4]

European Medicines Agency, 2013, QUEST ANSW POS SPEC

[5]

FDA, 2010, M ADV COMM PHARM SCI

[6]

FDA, 2012, IND PROD BIOEQ REC W

[7]

FDA, 2012, BIOEQ REC WARF SOD T

[8]

FDA, 2012, BIOEQ REC TACR CAPS

[9]

FDA, 2011, APPR DEM BIOEQ NARR

[10] Evaluation of a scaling approach for the bioequivalence of highly variable drugs [J].

Haidar S.H. ;

Makhlouf F. ;

Schuirmann D.J. ;

Hyslop T. ;

Davit B. ;

Conner D. ;

Yu L.X. .

The AAPS Journal, 2008, 10 (3) :450-454

← 1 2 →