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1、J:!GUIDANC4964dft.doc 07/10/02 Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products General Considerations DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document sh
2、ould be submitted within 30 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be iden
3、tified with the docket number listed in the notice of availability that publishes in the Federal Register. For questions regarding this draft document contact (CDER) Aida Sanchez 301-827-5847. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Re
4、search (CDER) July 2002 BP J:!GUIDANC4964dft.doc 07/10/02 Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products General Considerations Additional copies are available from: Office of Training and Communication Division of Drug Information, HFD-240 Cen
5、ter for Drug Evaluation and Research Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 (Tel) 301-827-4573 http:/www.fda.gov/cder/guidance/index.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) July 2002 BP J
6、:!GUIDANC4964dft.doc 07/10/02 TABLE OF CONTENTS I.INTRODUCTION. 1 II.BACKGROUND. 2 A.General.2 B.Bioavailability.3 C.Bioequivalence4 III. METHODS TO DOCUMENT BA AND BE 6 A.Pharmacokinetic Studies.6 B.Pharmacodynamic Studies10 C.Comparative Clinical Studies10 D.In Vitro Studies.10 IV. COMPARISON OF B
7、A MEASURES IN BE STUDIES.11 V.DOCUMENTATION OF BA AND BE.12 A.Solutions.12 B.Suspensions.13 C.Immediate-Release Products: Capsules and Tablets .13 D.Modified-Release Products14 E.Miscellaneous Dosage Forms.17 VI. SPECIAL TOPICS18 A.Food-Effect Studies.18 B.Moieties to Be Measured.18 C.Long Half-Life
8、 Drugs20 D.First Point Cmax.20 E.Orally Administered Drugs Intended for Local Action.20 F.Narrow Therapeutic Range Drugs21 ATTACHMENT A: General Pharmacokinetic Study Design and Data Handling .22 Draft Not for Implementation J:!GUIDANC4964dft.doc 07/10/02 1 GUIDANCE FOR INDUSTRY1 Bioavailability and
9、 Bioequivalence Studies for Orally Administered Drug Products General Considerations This draft guidance represents 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. An
10、 alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations. I.INTRODUCTION This guidance is intended to provide recommendations to sponsors and/or applicants planning to include bioavailability (BA) and bioequivalence (BE) information for
11、 orally administered drug products in investigational new drug applications (INDs), new drug applications (NDAs), abbreviated new drug applications (ANDAs), and their supplements. This guidance is a revision of the October 2000 guidance. This revised guidance changes recommendations regarding (1) st
12、udy design and dissolution methods development, (2) comparisons of BA measures, (3) the definition of proportionality, and (4) waivers for bioequivalence studies. The guidance also makes other revisions for clarification. The revisions should provide better guidance to sponsors conducting BA and BE
13、studies for orally administered drug products. This guidance contains advice on how to meet the BA and BE requirements set forth in part 320 (21 CFR part 320) as they apply to dosage forms intended for oral administration.2 The guidance is also generally applicable to non-orally administered drug pr
14、oducts where reliance on systemic exposure measures is suitable to document BA and BE (e.g., transdermal delivery systems and certain rectal and nasal drug products). The guidance should be useful for applicants planning to conduct BA and BE studies during the IND period for an NDA, BE studies inten
15、ded for submission in an ANDA, and BE studies conducted in the postapproval period for certain changes in both NDAs and ANDAs.3 1 This guidance has been prepared by the Biopharmaceutics Coordinating Committee in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (
16、FDA). 2 These dosage forms include tablets, capsules, solutions, suspensions, conventional/immediate release, and modified (extended, delayed) release drug products. 3 Other Agency guidances are available that consider specific scale-up and postapproval changes (SUPAC) for different types of drug products to help satisfy regulatory requirements in part 320 and 314.70 (21 CFR 314.70). Draft Not for Implementation J:!GUIDANC4964dft.doc 07/10/02 2 II. BACKGROUND A.General S
