■ For uncomplicated drugs in immediate release dosage forms, BE must be demonstrated under fasted conditions. In addition to a BE study under fasting conditions, we recommend 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) 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.
■ When the reference listed product label does not make any statements about the effect of food on absorption or administration.
■ For complicated drugs in immediate release dosage forms, e.g., narrow therapeutic range drugs (drugs with a steep dose-response curve, critical drugs), highly toxic drugs and drugs known to have nonlinear PKss. BE must be demonstrated under both fasted and fed conditions.
■ Nonlinear drugs. BE must be demonstrated under both fasted and fed conditions unless the nonlinearity occurs after the drug enters the systemic circulation and there is no evidence that the product exhibits a food effect.
■ Drugs in modified release dosage forms. BE must be demonstrated under both fasted and fed conditions.
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