Several publications in academic journals have focused on the difference between bioavailability and bioequivalence. Most of these suggest that at least some degree of confusion prevails about the exact nature of these two methods routinely used in drug development. These are similar, but not the same and each serves a different purpose. Here’s a guide to help you understand.
Part 320.1 of chapter 21 of the Codes of Federal Regulations (CFR) defines bioavailability of drugs as the rate and extent to which the active moiety of a drug product remains available at the intended site of action. It mostly applies to drugs administered orally.
The bioavailable fraction (F) is that part of the administered dose that reaches systemic circulation. The quantity of that F and the speed at which it can reach blood or plasma determines the efficacy of a drug.
Bioavailability studies usually apply two methods of measurement. Measuring the area under the blood or plasma concentration-time curve (AUC) is one method. Maximum concentration (Cmax) is the other measurement method.
The bioavailability of drugs is 100% through intravenous (IV) administration. Absolute bioavailability compares the availability of the therapeutic substance in systemic circulation when administered through a non-IV route such as oral with that of the IV route.
Relative bioavailability compares the availability of the active moiety in systemic circulation in one formulation with another formulation of the same drug. One of the formulations is usually an established standard. The same drug as a capsule and a tablet, for example.
The draft industry guidance developed by the U.S. Food and Drug Administration (FDA) in 2014 mentions that bioavailability studies are necessary for the process of new drug development to understand the safety and efficacy of any drug product.
That applies to any product under consideration for investigational new drug application (INDA), new drug application (NDA) and NDA supplements.
The FDA recommends documenting a systemic exposure profile of bioavailability to reflect two aspects. The release of the therapeutic element from the drug product and the series of potential pre systemic/systemic actions on the therapeutic substance post its release.
Bioequivalence refers to the comparability of two drugs. Two drugs are bioequivalent if there is no difference in their bioavailability profile when administered through the same route and in the same dose.
Bioequivalence studies reveal the compatibility or equivalence of the bioavailability of drugs – a new product and the reference drug. This is done through comparative bioavailability studies of the two drugs.
Bioequivalence has maximum relevance in the context of generic drugs. However, it also has applicability in the context of branded drugs. The bioequivalence of formulations used in early and late clinical trials, and between the formulations used in clinical trials and the drugs to be marketed is important.
One commonality between bioavailability and bioequivalence is that they both rely mostly on pharmacokinetic (PK) methods. However, bioequivalence is more a surrogate marker of therapeutic safety and efficacy since it is usually not necessary to repeat clinical trials for generic products.