Draft Guidance Temp 05/04/15 Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit electronic comments to http:/www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register. For questions regarding this draft document contact (CDER) Mehul Mehta 301-796-1573. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) May 2015 Biopharmaceutics Revision 1 Draft Guidance Temp 05/04/15 Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for Industry Additional copies are available from: Office of Communications, Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration 10001 New Hampshire Ave., Hillandale Bldg., 4th Floor Silver Spring, MD 20993-0002 Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 Email: druginfofda.hhs.gov http:/www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) May 2015 Biopharmaceutics Revision 1Contains Nonbinding Recommendations Draft Not for Implementation Draft Guidance Temp 05/04/15 TABLE OF CONTENTS I. INTRODUCTION. 1 II. THE BIOPHARMACEUTICS CLASSIFICATION SYSTEM . 2 A. Solubility . 3 B. Permeability . 3 C. Dissolution 3 III. RECOMMENDED METHODOLOGY FOR CLASSIFYING A DRUG SUBSTANCE AND FOR DETERMINING THE DISSOLUTION CHARACTERISTICS OF A DRUG PRODUCT . 3 A. Determining Drug Substance Solubility Class 3 B. Determining Drug Substance Permeability Class . 4 1. Pharmacokinetic Studies in Humans 4 2. Intestinal Permeability Methods . 5 3. Instability in the Gastrointestinal Tract 7 C. Determining Drug Product Dissolution Characteristics and Dissolution Profile Similarity 7 IV. BIOWAIVERS BASED ON BCS 8 V. ADDITIONAL CONSIDERATIONS FOR REQUESTING A BIOWAIVER . 9 A. Excipients 9 B. Prodrugs . 9 C. Fixed Dose Combinations 10 D. Exceptions . 10 1. Narrow Therapeutic Range Drugs 10 2. Products Designed to be Absorbed in the Oral Cavity . 10 VI. REGULATORY APPLICATIONS OF THE BCS 11 A. INDs/NDASs . 11 B. ANDAs 11 C. Supplemental NDAs/ANDAs (Postapproval Changes) . 11 VII. DATA TO SUPPORT A REQUEST FOR BIOWAIVERS 12 A. Data Supporting High Solubility 12 B. Data Supporting High Permeability . 12 C. Data Supporting Rapid, Very Rapid, and Similar Dissolution 13 D. Additional Information . 13 ATTACHMENT A . 14 Contains Nonbinding Recommendations Draft Not for Implementation Draft Guidance Temp 05/04/15 1 Waiver of In Vivo Bioavailability and Bioequivalence Studies for 1 Immediate-Release Solid Oral Dosage Forms Based on a 2 Biopharmaceutics Classification System 3 Guidance for Industry1 4 5 6 This draft guidance, when finalized, will represent the Food and Drug Administrations (FDAs) current 7 thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 8 bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of 9 the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA 10 staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call 11 the appropriate number listed on the title page of this guidance. 12 13 14 15 16 I. INTRODUCTION 17 18 This guidance provides recommendations for sponsors of investigational new drug applications 19 (INDs), and applicants that submit new drug applications (NDAs), abbreviated new drug applications 20 (ANDAs), and supplements to these applications for immediate-release (IR) solid oral dosage forms, 21 and who wish to request a waiver of in vivo bioavailability (BA) and/or bioequivalence (BE) studies. 22 These waivers are intended to apply to: (1) subsequent in vivo BA or BE studies of formulations 23 after the initial establishment of the in vivo BA of IR dosage forms during the IND period, and (2) in 24 vivo BE studies of IR dosage forms in ANDAs. 25 26 Regulations at 21 CFR part 320 address the requirements for BA and BE data for approval of drug 27 applications and s