Statistical Evaluation of Nonprofile Analyses for In Vitro Bioequivalence

• Activity Number: 256
• Type: Contributed
• Date/Time: Monday, August 2, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Jen-pei Liu*+
• Companies: National Taiwan University
• Keywords: Nasal Aerosols ; Nasal Sprays ; In Vitro Bioequivalence ; Population Bioequivalence ; Modified Large Samples ; Generalized Pivotal Quantities

Abstract

For locally acting drug products such as nasal aerosols and nasal sprays, the 2003 US FDA draft guidance suggests that bioequivalence between generic and innovator's products be established through in vitro tests. For non-profile analyses, the linearized population bioequivalence (PBE) criterion in the draft guidance does not take into consideration the variations due to lot, samples, and life stages. Under a two-stage nested random-effect model, we apply the methods of modified large samples and generalized pivotal quantities to construct the upper 95% confidence limit with consideration of variance components as statistical testing procedures. A simulation study was conducted to investigate empirical size and power. The issue of sample size determination with allocation to lot, sample, and life stage was also explored. A numerical example illustrates the proposed methods.