Bioavailability

Bioavailability (BA) is the rate and extent to which an active ingredient or active moiety becomes available following administration of a drug product. For products intended to produce a systemic effect, bioavailability is generally evaluated by measuring drug exposure in the systemic circulation. For locally acting products, FDA regulations permit bioavailability assessment using scientifically valid measurements of availability at the site of drug action.

FDA guidance describes bioavailability studies submitted in support of investigational new drug (IND) applications and new drug applications (NDAs) 1.

Regulatory definitions

US FDA

Under 21 CFR 314.3, bioavailability is defined as:

Bioavailability is the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of drug action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by scientifically valid measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of drug action 2.

The definition in 21 CFR 314.3 is referred to from 21 CFR part 320, which establishes FDA requirements concerning bioavailability and bioequivalence 3.

EMA

The European Medicines Agency defines bioavailability as:

The extent to which an active ingredient is absorbed from a medicine and becomes available in the body 4.

Measurements

In vivo bioavailability may be measured using parameters such as the concentration of the active drug ingredient in the blood, urinary excretion rates, or pharmacological effects.

Types of Bioavailability

Absolute bioavailability compares the systemic availability of an active substance from a particular dosage form and route of administration with its availability following intravenous administration, which is conventionally treated as 100% systemic availability.

Relative bioavailability compares the systemic availability of an active substance from two different dosage forms or routes of administration when an intravenous reference is not used. (EMA guidance gives comparison of a tablet with an oral solution as an example of relative bioavailability.)

Bioavailability and bioequivalence

Bioavailability describes the exposure produced by a medicinal product, whereas bioequivalence compares the bioavailability of two pharmaceutical products containing the same active substance or active moiety. Bioequivalence assessments generally examine whether the rate and extent of absorption differ between the products within predefined criteria.

Related terminology

  • Bioequivalence
  • Investigational product
  • Pharmacokinetics

References

  1. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. 2022. Bioavailability Studies Submitted in NDAs or INDs – General Considerations. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioavailability-studies-submitted-ndas-or-inds-general-considerations ↩︎
  2. U.S. Food and Drug Administration. 21 CFR Part 314 Applications for FDA Approval to Market a New Drug. Available at: https://www.ecfr.gov/current/title-21/part-314 ↩︎
  3. U.S. Food and Drug Administration. 21 CFR § 320.23 Basis for measuring in vivo bioavailability or demonstrating bioequivalence. Available at: https://www.ecfr.gov/current/title-21/section-320.23 ↩︎
  4. European Medicines Agency. Bioavailability. Available at: https://www.ema.europa.eu/en/glossary-terms/bioavailability ↩︎