FDA Announces Availability of a Draft Guidance: “Bioavailability Studies Submitted in NDAs or INDs — General Considerations”

On February 25, 2019, the U.S. Food and Drug Administration (FDA) announced the availability of a draft guidance for industry entitled “Bioavailability Studies Submitted in NDAs or INDs — General Considerations”. This guidance provides recommendations to sponsors submitting bioavailability (BA) information for drug products in investigational new drug applications (INDs), new drug applications (NDAs), and NDA supplements.

This guidance contains advice on how to meet the BA regulatory requirements as they apply to dosage forms intended for oral administration. The guidance is also applicable to non-orally administered drug products when it is appropriate to rely on systemic exposure measures to determine the BA of a drug (e.g., transdermal delivery systems and certain rectal and nasal drug products). It provides advice on conducting relative BA studies during the IND period for a drug intended to be submitted for approval in an NDA and bioequivalence (BE) studies during the post-approval period for certain changes to drug products. The guidance outlines recommendations regarding considerations for study design, assessing BA for various dosage forms, information on in vitro approaches, and discusses special topics.

Determining the BA of formulations is important during the life cycle of drug products and aids in the FDA’s evaluation of the safety and effectiveness of a product in an IND, NDA, or NDA supplements. 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 provide an estimate of the fraction of the drug absorbed as well as information related to the pharmacokinetics of the drug, such as distribution, metabolism, excretion, the effects of food on the absorption of the drug, dose proportionality or linearity in the pharmacokinetics of the active moieties and, when appropriate, inactive moieties. 

When finalized, this guidance will revise and replace the FDA’s March 2014 draft guidance for industry entitled “Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — General Considerations”, which addresses BA or BE studies for INDs, NDAs, and NDA supplements. The FDA recognizes that the “Bioavailability Studies Submitted in NDAs or INDs — General Considerations” guidance cannot address every issue pertaining to the assessment of BA studies for INDs and NDAs. Therefore, sponsors are encouraged to contact the appropriate review division for guidance on specific questions not addressed by this guidance.

The “Bioavailability Studies Submitted in NDAs or INDs — General Considerations” guidance is available at https://go.usa.gov/xEyuY. Please refer to the guidance for more details.

FDA is publishing this draft guidance to collect additional public comments. You may submit your comments to the draft guidance by May 28, 2019 to the docket (Docket No. FDA-2018-D-4367) available at https://www.regulations.gov. Your comments do make a difference and can impact the outcomes of FDA regulatory policy. Share your knowledge and experience, and make your voice count.

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.