BEHAVIOR OF INDIVIDUAL BE

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SOME FEATURES, ISSUES, AND PROBLEMS
OF INDIVIDUAL BIOEQUIVALENCE
Laszlo Endrenyi and Laszlo Tothfalusi University
of Toronto
FDA/CDER Advisory Committee for
Pharmaceutical Science November 29, 2001
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BEHAVIOR OF INDIVIDUAL BE

• Individual BE has, in practice, unfavorable
  properties
• Acceptance or rejection can be due to random
  chance alone

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HIGHLY-VARIABLE DRUGS

• Replicate design is recommended
• Analysis outlined in Guidances
• only by scaled individual BE
• But scaled average BE is much more effective

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For the comparison of means Scaled average
BE scABE4 is much more effective than
scaled individual BE scIBE4 (smaller
consumer and producer risks)
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When two criteria are applied jointly, the rate
of acceptance is less than that of either
component criterion alone e.g., scaled
individual BE scIBE 4 and GMR1.25
GMR_limit In this case, the joint criterion
GIBE 4_sc is essentially a GMR criterion
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CONSTRAINT ON RATIO OF GEOMETRIC MEANS (GMR)
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FIRST SET OF CONCLUSIONSON INDIVIDUAL
BIOEQUIVALENCE
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BE OF MODIFIED-RELEASE (MR)FORMULATIONS
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BE OF MODIFIED-RELEASE (MR)FORMULATIONS
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SUBJECT-BY-FORMULATIONINTERACTION (SF)
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DATA ANALYSIS STATISTICAL METHODOLOGYSuggested
projects