Tests carried out using an analysis of variance and calculating a 90% confidence interval (CI) for the average of each pharmacokinetic parameter must be entirely within the 80% to 125% boundaries. The limit expressed in the second analysis is 125%, which is the reciprocal of 80%. 4 All data are expressed as a ratio of the average response (AUC and Cmax) for test and/or reference. The core of the bioequivalence concept is an absence of a significant difference, which is considered to be less than 20% by the FDA. The FDA uses an average bioequivalence approach involving a comparison of means when it is determining a product’s bioequivalence.

Laws Concerning Bioequivalence and NTI Drugs Such drugs have less than a twofold difference in the minimum toxic concentration and minimum effective concentration in the blood or are those drug product formulations that exhibit limited or erratic absorption, formulation-dependent bioavailability, and wide intrapatient pharmacokinetic variability that requires blood-level monitoring.” 2 As defined by the Therapeutic Products Directorate of Health Canada, an NTR drug is a drug wherein the ratio of the lowest concentration at which clinical toxicity occurs, to the median concentration providing a therapeutic effect, is less than or equal to two. The North Carolina Board of Pharmacy defines an NTI drug as “those pharmaceuticals having a narrowly defined range between risk and benefit.

Therapeutic index