[Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR320.23]

[Page 189-190]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                           SERVICES--Continued
 
PART 320--BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS--Table of Contents
 
      Subpart B--Procedures for Determining the Bioavailability or 
                     Bioequivalence of Drug Products
 
Sec. 320.23  Basis for demonstrating in vivo bioavailability or bioequivalence.

    (a)(1) The in vivo bioavailability of a drug product is demonstrated 
if the product's rate and extent of absorption, as determined by 
comparison of measured parameters, e.g., concentration of the active 
drug ingredient in the blood, urinary excretion rates, or 
pharmacological effects, do not indicate a significant difference from 
the reference material's rate and extent of absorption. For drug 
products that are not intended to be absorbed into the bloodstream, 
bioavailability may be assessed by measurements intended to reflect the 
rate and extent to which the active ingredient or active moiety becomes 
available at the site of action.
    (2) Statistical techniques used shall be of sufficient sensitivity 
to detect differences in rate and extent of absorption that are not 
attributable to subject variability.
    (3) A drug product that differs from the reference material in its 
rate of absorption, but not in its extent of absorption, may be 
considered to be bioavailable if the difference in the rate of 
absorption is intentional, is appropriately reflected in the labeling, 
is not essential to the attainment of effective body drug concentrations 
on chronic use, and is considered medically insignificant for the drug 
product.
    (b) Two drug products will be considered bioequivalent drug products 
if they are pharmaceutical equivalents or pharmaceutical alternatives 
whose rate and extent of absorption do not show a significant difference 
when administered at the same molar dose of the active moiety under 
similar experimental conditions, either single dose or multiple dose. 
Some pharmaceutical equivalents or pharmaceutical alternatives may be 
equivalent in the extent of their absorption but not in their rate of 
absorption and yet may be considered bioequivalent because such 
differences in the rate of absorption are

[[Page 190]]

intentional and are reflected in the labeling, are not essential to the 
attainment of effective body drug concentrations on chronic use, and are 
considered medically insignificant for the particular drug product 
studied.

[57 FR 17999, Apr. 28, 1992]