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Appendix IX: An Alternative Solution to the Distribution of the Individual Bioequivalence Metric

The Office of Generic Drugs (OGD) of the Federal Drug Administration (FDA) has recently published statistical guidelines for determination of bioequivalence (1), see above. Included in that publication is a statistical approach to determining individual bioequivalence (IB), as recommended by Hyslop et al. (1). Herewith, is a description of an alternative approach. The probability density function (PDF) of the IB metric is determined and used to construct a decision rule for acceptance. The acceptance criterion is based on an upper 95% confidence interval for the metric, defined as 2.4948. Here is shown the derivation here for the reference-scaled metric. However, with minor modifications, this approach is also applicable to the constant denominator metric and to population bioequivalence described in the FDA Guidance (1). The following has been described in Chapter 11, but is repeated here for the sake of continuity.