Bioavailability Studies for NDA or IND Guidance

06/07/2022

The US Food and Drug Administration (FDA) released a guidance “Bioavailability Studies Submitted in NDAs or INDs – General Considerations” in April 2022. Bioavailability (BA) is defined as “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 action.” BA data estimate the amount of drug absorbed, the effects of food on absorption, and other information related to the pharmacokinetics. Understanding the BA helps the FDA in evaluating the safety and effectiveness of a drug product. To make a determination, the FDA reviews the clinical trial data, the BA data, and the exposure-response evaluations. For more information on exposure-response data used for INDs and BLAs, refer to the guidance “Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications” from May 2003.

The final guidance provides recommendations on how to meet the BA requirements. Sections include the following:

  • Study design considerations

  • Assessing BA and demonstrating Bioequivalence for various dosage forms

  • Additional information on in vitro approaches used in support of BA

  • Special topics, such as narrow therapeutic index drugs

It also includes appendixes that outline study design recommendations:

  • General study design and data handling

  • Guidelines for conducting fed or fasted studies

  • Guidelines for conducting an in vitro alcohol dose-dumping study

This guidance focuses on BA for oral drugs and recommends healthy, fasting volunteers using a single-dose, in vivo study. It also describes when multiple-dose, in vivo BA studies are appropriate, and that confirmation of steady-state concentrations should be documented.

 

- The Clinical Pathways Team

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