FREQUENTLY Asked Questions

When should food-effect bioavailability (BA) and bioequivalence (BE) studies be conducted?

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About the Author
Proxima CRO Team
Isabella Schmitt, RAC
Director of Regulatory Affairs
Ms. Schmitt has also served in additional regulatory affairs and clinical research roles in which she contributed to multiple regulatory submissions and clinical affairs projects across a wide range of indications.

For Immediate-Release Drug Products

1. INDs/NDAs

FDA recommends that a food-effect BA study be conducted for all new chemical entities (NCEs) during the IND period.

Food-effect BA studies should be conducted early in the drug development process to guide and select formulations for further development. Food-effect BA information should be available to design clinical safety and efficacy studies and to provide information for the clinical pharmacology and/or dosage and administration sections of product labels. If a sponsor makes changes in components, composition, and/or method of manufacture in the clinical trial formulation prior to approval, bioequivalence (BE) should be demonstrated between the to-be-marketed formulation and the clinical trial formulation.

Sponsors may wish to use relevant principles described in the guidance for industry on SUPAC-IR: Immediate Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation (SUPAC-IR guidance) to determine if in vivo BE studies are recommended. These BE studies, if indicated, should generally be conducted under fasting conditions.

2. ANDAs

In addition to a BE study under fasting conditions, FDA recommends a BE study under fed conditions for all orally administered immediate-release drug products, with the following exceptions:

  • When both test product and RLD are rapidly dissolving, have similar dissolution profiles, and contain a drug substance with high solubility and high permeability (BCS Class I) (see footnote 3), or
  • When the dosage and administration section of the RLD label states that the product should be taken only on an empty stomach, or
  • When the RLD label does not make any statements about the effect of food on absorption or administration.

For Modified-Release Drug Products

We recommend that food-effect BA and fed BE studies be performed for all modified release dosage forms.

1. INDs/NDAs

FDA recommends a study comparing the BA under fasting and fed conditions for all orally administered modified-release drug products. When changes occur in components, composition, and/or method of manufacture between the to-be-marketed formulation and the primary clinical trial material, the sponsor may wish to use relevant principles described in the guidance for industry on SUPAC-MR: Modified Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing, and Controls: In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation (SUPAC-MR guidance) to determine if documentation of in vivo BE is recommended. These BE studies, if indicated, should generally be conducted under fasting conditions.

2. ANDAs

In addition to a BE study under fasting conditions, a BE study under fed conditions should be conducted for all orally administered modified-release drug products.

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