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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