Bioequivalence and Bioavailability Forum

❝ a. the 95% upper confidence bound for (Yt-Yr)^2 -ØS^2 must be ≤ 0

❝

❝ My question is Why only upper limit is consider for acceptance criteria?

–θ_s ≤ (μ_T – μ_R) ∕ σ_W ≤ θ_s

(μ_T – μ_R)² – θ_s²·σ_W² ≤ 0.

• Hyslop T, Hsuan F, Holder DJ. A small sample confidence interval approach to assess individual bioequivalence. Stat Med. 2000;19(20):2885–97. doi 10.1002/1097-0258(20001030)19:20<2885::AID-SIM553>3.0.CO;2-H
  
• Haidar SH et al. Bioequivalence Approaches for Highly Variable Drugs and Drug Products. Pharm Res. 2008;25(1):237–41. doi 10.1007/s11095-007-9434-x
  
• Haidar SH et al. Evaluation of a Scaling Approach for the Bioequivalence of Highly Variable Drugs. AAPS J. 2008;10(3):450–4. doi 10.1208/s12248-008-9053-4
  
• Endrényi L, Tóthfalusi L.Regulatory conditions for the determination of bioequivalence of highly variable drugs. J Pharm Pharm Sci. 2009;12:138–49. free online
  
• Tóthfalusi L, Endrényi L, García-Arieta A. Evaluation of Bioequivalence for Highly Variable Drugs with Scaled Average Bioequivalence. Clin Pharmacokinet. 2009;48(11):725–43. doi 10.2165/11318040-000000000-00000
  
• Karalis V, Symillides M, Macheras P. Bioequivalence of Highly Variable Drugs: A Comparison of the Newly Proposed Regulatory Approaches by FDA and EMA. Pharm Res. 2012;29(4):1066–77. doi 10.1007/s11095-011-0651-y