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.
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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.
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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
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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
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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.
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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.
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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.
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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.
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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.
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11.
11Chalapathi Institute of Pharmaceutical Sciences, Lam GUNTUR