Statistical Evaluation of Similarity Factor f 2 as a Criterion for Assessment of Similarity Between Dissolution Profiles
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Information Journal, Vol. 31, pp. 1255-1271, 1997 Printed in the USA. All rights reserved.
Drug
Copyright 0 1997 D m g Information Association Inc.
STATISTICAL EVALUATION OF SIMILARITY FACTOR fi AS A CRITERION FOR ASSESSMENT OF SIMILARITY BETWEEN DISSOLUTION PROFILES JEN-PEILIU, PHD Professor, Department of Statistics, National Cheng-kung University, Tainan, Taiwan, R.O.C.
MI-CHIAMA, PHD Associate Professor, Department of Statistics, National Cheng-kung University, Tainan, Taiwan, R.O.C.
SHEIN-CHUNG CHOW,PHD Executive Director, Biostatistics and Data Management. Covance. Inc., Princeton, New Jersey
This paper addresses statistical issues of similarity factorf, as a criterion for assessment of similarity between two in vitro dissolution profiles as proposed in “Guidance on Immediate Release Solid Oral Dosage Forms; Scale-up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing; In Vivo Bioequivalence Documentation” (SUPAC), issued by the United States Food and Drug Administration on November 30, 1995. These issues include the invariant property off2 with respect to the location change and the consequence of failure to take into account shape of the curve and unequal spacing between sampling time points. The similarity factor f, is a sample statistic which cannot be used to formulate a statistical hypothesis for assessment of dissolution similarity. It is, therefore, impossible to evaluate false positive and false negative rates of decisions for approval of drug products based on f,. Implementation of f2 to assess dissolution similarity is, in fact, a one-sided problem rather than an interval criterion suggested by the SUPAC. Complexity of the form in the distribution of f, even under a very strict assumption prevents one from finding its expected variance and hence, confidence interval for the mean. The large-sample distribution of f2 by the usual delta method fails to provide an adequate approximation to the empirical distribution obtained by simulation. In addition, simulation results also indicate that the similarity factor is too liberal in concluding similarity between dissolution profiles. Key Words: Dissolution; Similarity; Hypothesis; Distribution
INTRODUCTION IN “VO BIOEQUIVALENCE studies are surrogate trials for assessing equivalence between test and reference formulations based
Reprint address: Dr. Shein-Chung Chow, Executive Director, Biostatistics and Data Management, Covance, Inc., 210 Camegie Center, Princeton, New Jersey 08540.
on the rate and extent of drug absorption in humans without actually performing clinical trials to and safety because the fundamental bioequivalence assumption implies that bioequivalent formulations are therapeutically equivalent and can be used interchangeably (1). After a marketing9 drug is approved for there may be Some changes in chemistry, manufacturing, and controls for drug produc-
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Jen-pei Liu, Mi-Chia Ma, and Shein-Chung Chow
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