21CFR 320- BIO AVAILABILITY AND BIO EQUIVALENCE REQUIREMENTS
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The document outlines the requirements for bioavailability and bioequivalence as per the Code of Federal Regulations. It details the submission criteria to the FDA, guidelines for in vivo studies, and protocols for establishing bioequivalence. Additionally, it discusses sample retention policies and procedures for amending bioequivalence requirements.
21CFR 320- BIO AVAILABILITY AND BIO EQUIVALENCE REQUIREMENTS
- 1. CODE OF FEDERAL REGULATIONS 21 PART 320 BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Presented by: PALLAVI M M.PHARMACY 1ST YEAR.
- 2. INTRODUCTION: WHAT DO YOU MEAN BY BIOAVAILABILITY? The rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. WHAT IS BIOEQUIVALENCE? The assessment of the expected in vivo biological equivalence of two proprietary preparations of a drug. If two products are said to be bioequivalent it means that they would be expected to be, for all intents and purposes, the same. 2Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
- 3. REQUIREMENTS FOR SUBMISSION OF BIOAVAILABILITYAND BIOEQUIVALENCE DATA Submission of NDA application to FDA Submission of ANDA application to FDA Submission of supplemental application to FDA CRITERIA FOR A WAIVER OF EVIDENCE OF INVIVO BIOAVAILABILITYAND BIOEQUIVALENCE: Request to the FDA to waive the application regarding the changes. For certain drug products, the in vivo BA/BE of the drug product may be self evident. 3Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
- 4. GUIDELINES FOR THE CONDUCT OF AN INVIVO BIOAVAILABILITY STUDY Basic principle is “NO UNNECESSARY HUMAN RESEARCH” should be done. Critically ill patients shouldn’t be included. Comparison to a reference material Basic study design: I • scientific questions to be answered. II • nature of the reference material & dosage form tested. III • availability of analytical methods. IV • benefit-risk considerations 4 Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
- 5. GUIDELINES ON DESIGN OF A SINGLE DOSE INVIVO BA/BE STUDY: Bioavailability/bioequivalence study should be a single dose comparison of drug product & conducted in normal adults. Test product and reference material should be administered in fasting state. Study design: At least three times the half life of decay of pharmacological effect. At least three times the half life of a active ingredient. Should provide a drug elimination period 5 Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
- 6. GUIDELINES ON DESIGN OF MULTIPLE DOSE INVIVO BIOAVAILABILTY/BIOEQUIVALENCE STUDY Test product and reference sample to be compared after repeated administration to determine steady state levels. Difference in rate of absorption but not in extent of absorption. Excessive variability of bioavailability from subject to subject. CORRELATION OF BIOAVAILABILITY WITH ACUTE PHARMACOLOGICAL EFFECT: May be required if needed to establish the clinical significance of a special claim. e.g., in the case of an extended release preparation. 6Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
- 7. ANALYTICAL METHODS FOR AN INVIVO BA/BE STUDY: To measure the active ingredients in body fluids/ excretory products. INQUIRES REGARDING BA/BE REQUIREMENTS &REVIEW OF PROTOCOLS BY FDA: Any person conducting BA/BE studies must submit the proposed protocol for the study of FDA for review prior. APPLICABILITY OF REQUIREMENTS REGARDING ‘INDA’: Test product contains New Chemical Entity Study involves radio actively labeled drug product. Study involves cytotoxic drug product. 7Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
- 8. PROCEDURE FOR ESTABLISHING OR AMENDING A BIOEQUIVALENCE REQUIREMENT The FDA, on its own initiative may propose and promulgate a regulation to establish a bioequivalence requirement for a product not subject to section 505(j) of the act if it finds there is well-documented evidence that specific pharmaceutical equivalents or pharmaceutical alternatives intended to be used interchangeably for the same therapeutic effect: 1. The drugs are not bioequivalent drug products 2. May not be bioequivalent drug products because they are members of a class of drug products that have close structural similarity and similar physicochemical properties. A summary and analysis of relevant information that was submitted in the petition. 8Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
- 9. RETENTION OF BIOAVAILABILITY SAMPLES: 1. Reserve samples: these are the test samples and reference samples used by the either applicant or contract research organization to conduct BIOAVAILABILITY studies. 2. Retention of reserve samples is for 5 years. 3. Each reserve samples shall consist of a sufficient quantity t permit FDA to perform 5times of all the release tests required in application. 4. Storage of the reserve samples is as per labeling. 9Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
- 10. RETENTION OF BIOEQUIVALENCE SAMPLES: 1. If bioequivalence testing was performed under contract, the contract research organization shall retain reserve samples of any test article and reference standard used in conducting an in vivo or in vitro bioequivalence study required for approval of the abbreviated application or supplemental application. 2. Retention of samples are for 5years. 10Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR
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