When are fasting and fed bioequivalence studies required?

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SFDA: “In general, a bioequivalence study should be conducted under fasting conditions as this is considered to be the most sensitive condition to detect a potential difference between formulations.” (SFDA BE v3.1 · 3.1.4 Study conduct – Fasting or fed conditions) “For products where the SPC recommends intake of the reference medicinal product on an empty stomach or irrespective of food intake, the bioequivalence study should hence be conducted under fasting conditions. For products where the SPC recommends intake of the reference medicinal product only in fed state, the bioequivalence study should generally be conducted under fed conditions.” (SFDA BE v3.1 · 3.1.4 Study conduct – Fasting or fed conditions) “However, for products with specific formulation characteristics (e.g. microemulsions, solid dispersions), bioequivalence studies performed under both fasted and fed conditions are required unless the product must be taken only in the fasted state or only in the fed state. For modified release product, bioequivalence studies performed under both fasted and fed conditions are required.” (SFDA BE v3.1 · 3.1.4 Study conduct – Fasting or fed conditions) EU: “For a drug product that is labelled to be taken only under fasting conditions or can be taken under fasting or fed conditions, i.e., without regard to food, a single BE study conducted under fasting conditions is recommended to demonstrate BE.” (ICH M13A · 2.1.5) “For a drug product that is labelled to be taken only with food due to PK reasons, i.e., enhancing absorption or reducing variability, a single BE study conducted under fed conditions is recommended to demonstrate BE.” (ICH M13A · 2.1.5) “For these high-risk products, BE studies should be conducted under both fasting and fed conditions, irrespective of the drug product labelling with regard to food intake, if safety permits.” (ICH M13A · 2.1.5) US FDA: “For immediate-release drug products with a high risk of bioinequivalence due to food effect, FDA generally recommends that applicants conduct the following studies: (1) a single-dose, fasting BE study comparing the highest strength of the test product and reference standard; and (2) a single-dose, fed BE study comparing the highest strength of the test product and reference standard.” (FDA ANDA BE 2026 · IV.B.1) “For a drug product that is labeled to be taken only with food due to PK reasons, i.e., enhancing absorption or reducing variability, a single BE study conducted under fed conditions is recommended to demonstrate BE.” (FDA M13A · 2.1.5) “For all orally administered modified-release drug products, FDA recommends that applicants conduct BE studies under both fasting and fed conditions, irrespective of the RLD labeling regarding food intake.” (FDA ANDA BE 2026 · III.A.10) WHO: “Fasted-state studies are generally preferred. However, when the product is known to cause gastrointestinal disturbances if given to subjects in the fasted state, or if the labelling of the comparator product restricts administration to subjects in the fed state, then a fed-state study becomes the preferred approach.” (WHO TRS 1052 Annex 8 · 7.4.4 — Immediate-release formulations) “For products with specific formulation characteristics (such as microemulsions or solid dispersions), bioequivalence studies performed under both fasted and fed conditions are required, unless the product is only taken in a fasted or fed state.” (WHO TRS 1052 Annex 8 · 7.4.4 — Immediate-release formulations) “Therefore, bioequivalence studies conducted under both fasted and fed conditions are required for orally administered, modified-release pharmaceutical products.” (WHO TRS 1052 Annex 8 · 7.1.4)

When are fasting and fed bioequivalence studies required?

SFDA Saudi Food and Drug Authority

EU European Union

US FDA US Food and Drug Administration

WHO World Health Organization

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