FDA 华法令指导原则Warfarin Sodium.pdf

Contains Nonbinding Recommendations Draft Guidance on Warfarin Sodium This draft guidance, once finalized, will represent the Food and Drug Administrations (FDAs) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the Office of Generic Drugs. Active ingredient: Warfarin Sodium Form/Route: Tablet/Oral Recommended studies: 2 studies 1. Type of study: Fasting Design: 4-way, fully replicated crossover design in-vivo Strength: 10 mg Subjects: Healthy males and nonpregnant females, general population. Additional Comments: Warfarin has a long terminal elimination half-life. Please ensure adequate washout periods between treatments in the crossover studies. For long half-life drug products, an AUC truncated to 72 hours may be used in place of AUC0-t or AUC0-∞, as described in the Guidance for Industry: “Bioavailability and Bioequivalence Studies for Orally Administered Drug Products – General Considerations”. Applicants may consider using the reference-scaled average bioequivalence approach for warfarin described below. 2. Type of study: Fed Design: 4-way, fully replicated crossover design in-vivo Strength: 10 mg Subjects: Healthy males and nonpregnant females, general population. Additional Comments: See additional comments above. See Amantadine Hydrochloride Oral Tablet guidance for recommendation regarding fed studies. Analytes to measure (in appropriate biological fluid): Warfarin in plasma, using an achiral assay. Bioequ