Understanding the concepts of bioavailability and bioequivalence testing is essential in the drug development process because they create the foundation for regulatory decision making when evaluating formulation changes and lot-to-lot consistency in innovator products. They also serve as the primary components to demonstrate therapeutic equivalence between generic products and the reference innovator product.
Bioequivalence is an important consideration in ensuring lot to lot consistency, including whenever evaluating changes in a marketed product’s formulation, manufacturing process, and dosage strength. Bioequivalence is also critical in regulatory authority decision making when determining whether a generic product is therapeutically equivalent to the original innovator product.
Bioavailability is a term that indicates measurement of both the rate of drug absorption and the total amount (extent) of drug that reaches the systemic circulation from an administered dosage form. It is specific to the parent or active drug substance as contrasted to metabolites.
Bioequivalence indicates that a drug in two or more similar dosage forms reaches the systemic circulation at the same relative rate and extent (i.e., the plasma level profiles of the drug obtained using the two dosage forms are the same).
Area under the Concentration–Time Curve (AUC) is the integral of the concentration–time curve after administration of a single dose of drug or after achieving a steady state. The calculated area under the serum, blood, or plasma concentration–time curve is reported in amount/volume multiplied by time (e.g., μg/mL × h or g/100 mL × h) and can be considered representative of the amount of drug absorbed. Several variants of AUC exist, including AUC0-t; AUC0-∞; and AUCτ, SS, corresponding to the calculated area from time zero to a truncated time point (e.g., AUC0-48), the total area under the curve, and the area when steady state has been achieved.
Peak-height Concentration (Cmax) is the peak of the blood level–time curve and represents the highest drug concentration achieved after drug administration.
Time of Peak Concentration (Tmax) is the measured length of time necessary to achieve the maximum concentration (Cmax) after drug administration.